Cryptococci

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 Immunodeficiency Syndrome . We observed 14 cases of CMV retinitis, 2 cases of toxoplasmic chorioretinitis, 1 case of cryptococcal choroiditis and 2 cases of herpes zoster retinitis . Review of the clinical, angiographical and histopathological aspects of these infections . Review of the vital and visual prognosis after treatment.

Pharmacol Ther, 1995, 67(1), 79 - 100
P450 inhibitors of use in medical treatment: focus on mechanisms of action; Vanden Bossche H et al.; A number of cytochrome P450s are targets for compounds that are clinically used or under clinical evaluation for treatment of patients with mycotic infections, such as dermatophytosis, superficial and systemic candidiasis, cryptococcosis and aspergillosis, with skin diseases, such as psoriasis or ichthyosis, and other retinoid-sensitive malignancies, e.g., neuro-ectodermal glioma . Some of the P450 inhibitors are candidates for the treatment of hirsutism or prostate cancer, others are potent inhibitors of the P450 isomerase involved in the synthesis of thromboxane A2, a potent platelet aggregation inducer and vasoconstrictor.

J Immunol, 1994 Dec 15, 153(12), 5790 - 801
Macrophage function in simian AIDS . Killing defects in vivo are independent of macrophage infection, associated with alterations in Th phenotype, and reversible with IFN-gamma; Brodie SJ et al.; Infection of macrophages (M phi) in vitro with M phi-tropic isolates of simian immunodeficiency virus (SIV) did not affect killing of Cryptococcus neoformans up to 16 days after inoculation (p < 0.05) . Conversely, alveolar M phi from animals with SIV-induced AIDS killed C . neoformans less efficiently (10.4 +/- 2.8% killing) and, when stimulated with phorbol myristate, produced less superoxide anion (O2-; 0.15 +/- 0.02 O2-/h/mg M phi protein) than M phi from uninfected monkeys (21.8 +/- 1.6% killing and 0.29 +/- 0.02 O2-/h/mg M phi protein) . In contrast, killing and O2- release were accentuated in SIV+ asymptomatic animals (25.8 +/- 2.3% killing and 0.40 +/- 0.04 O2-/h/mg M phi protein; p < 0.05) . M phi-mediated killing and O2- production could be restored by culturing the affected cells in supernatants derived from Con A-stimulated PBMC of uninfected or SIV+ asymptomatic monkeys . Supernatants with restorative properties had high IFN-gamma bioactivity (63.4 +/- 11.0 U/ml) and elevated IL-10 concentrations (75.3 +/- 10.4 pg/ml) as compared with PBMC supernatants derived from animals with AIDS (IFN-gamma, 9.7 +/- 4.9 U/ml; IL-10, 24.0 +/- 10.1 pg/ml) . Functional restoration was found to be dependent, in part, on the presence of IFN-gamma, as neutralizing Abs to IFN-gamma significantly inhibited functional restoration in active supernatants . Moreover, the inactivity of supernatants from mitogen-stimulated PBMC cultures derived from animals with AIDS was not solely dependent upon the loss of CD4+ lymphocytes, inasmuch as purified pulmonary alveolar and peripheral blood CD4+ T cells from only uninfected and SIV+ asymptomatic animals, and not those from animals with AIDS, produced IFN-gamma upon mitogen stimulation . Collectively, these findings suggest that functional aberrations in alveolar M phi from animals with AIDS are not directly due to virus infection but likely result from changes in the pulmonary microenvironment in association with the multisystemic loss and dysfunction of CD4+ T cells.

Gene, 1994 Dec 15, 150(2), 221 - 6
Cloning, expression and characterization of thymidylate synthase from Cryptococcus neoformans; Livi LL et al.; The thymidylate synthase (TS)-encoding gene from Cryptococcus neoformans (Cn) has been isolated from cDNA and genomic libraries . The 1127-bp gene contains three introns and a 951-bp open reading frame encoding a 35,844-Da protein . The cDNA clones lack 324 bp of the 5' coding region of the gene . The complete coding sequence was assembled as an expression cassette in pUC19 using parts of the coding sequence from the cDNA and genomic DNA and completing the sequence using synthetic DNA . Production of active TS from Cn (CnTS) was first demonstrated by complementation of a thymine(Thy)-requiring Escherichia coli strain . The expression cassette was subsequently subcloned into the T7 polymerase vector pET15-b . In this construct, CnTS is produced as approximately 10% of the total soluble protein in E . coli . Homogeneous enzyme was obtained at a 36% yield after consecutive chromatography on DEAE-cellulose, Q-Sepharose, phenyl-Sepharose and Affi-Gel Blue . Steady-state kinetic analysis showed that the Km values for dUMP and CH2H4.folate were 2.7 +/- 0.5 microM and 38.2 +/- 2.5 microM, respectively, and the kcat was 5.1 s-1 . The enzyme was stable upon storage at -80 degrees C in Tris.HCl pH 7.4 and thiol.

Proc Natl Acad Sci U S A, 1994 Dec 6, 91(25), 12008 - 12
Targeted gene replacement demonstrates that myristoyl-CoA: protein N-myristoyltransferase is essential for viability of Cryptococcus neoformans; Lodge JK et al.; Cryptococcus neoformans is a major cause of systemic fungal infection in immunocompromised patients . Myristoyl-CoA:protein N-myristoyltransferase (Nmt) catalyzes the transfer of myristate (C14:0) from myristoyl-CoA to the N-terminal glycine of a subset of cellular proteins produced during vegetative growth of C . neoformans . A Gly487-->Asp mutation was introduced into C . neoformans NMT by targeted gene replacement . The resulting strains are temperature-sensitive myristic acid auxotrophs . They are killed at 37 degrees C when placed in medium lacking myristate and, in an immunosuppressed animal model of cryptococcal meningitis, are completely eliminated from the subarachnoid space within 12 days of initial infection . C . neoformans and human Nmts exhibit differences in their peptide substrate specificities . These differences can be exploited to develop a new class of fungicidal drugs.

Am J Med, 1994 Dec, 97(6), 515 - 22
The continuing utility of bronchoalveolar lavage to diagnose opportunistic infection in AIDS patients; Baughman RP et al.; PURPOSE: To determine whether bronchoalveolar lavage (BAL) remains a useful technique in assessing human immunodeficiency virus (HIV)-infected patients with pulmonary symptoms . PATIENTS AND METHODS: All HIV-infected patients with pulmonary symptoms referred to a university hospital-based pulmonary service underwent bronchoscopy and BAL within 24 hours of referral . All samples were handled in a standardized fashion . The results of the lavage were compared with chest roentgenograms and clinical results . RESULTS: A total of 894 lavages were performed on HIV-infected patients over a 7-year period . The overall diagnostic yield was 60%, with 420 patients having Pneumocystis carinii . Infections other than P carinii were found in 185 cases, including 75 lavages with P carinii and another infection . The other infections included Mycobacterium tuberculosis (17 patients), Mycobacterium kansasii (15 patients), Histoplasma capsulatum (24 patients), Cryptococcus neoformans (17 patients), and bacterial infection (103 patients) . For 364 lavages, no diagnosis was made . Chest roentgenograms were not useful in predicting what infection would be diagnosed . There was no difference in the yield of BAL over the 7-year period, despite the introduction of aerosol pentamidine prophylaxis and antiretroviral therapy . CONCLUSION: Bronchoscopy with BAL continues to have a role in the evaluation of HIV-infected patients with pulmonary symptoms.

Infect Immun, 1994 Dec, 62(12), 5694 - 7
Genetic study of oxygen resistance and melanization in Cryptococcus neoformans; Emery HS et al.; Genetic analysis of oxygen-sensitive mutants of Cryptococcus neoformans revealed two loci (oxy1 and oxy2) linking hyperoxia sensitivity to production of melanin, a known virulence factor . Hyperoxia-sensitive strain 562 (oxy1 oxy2) is albino and avirulent . oxy2-defective strains lacking the oxy1 defect are melanin deficient but show normal hyperoxia resistance . Mutants defective at three additional mapped melanin loci fail to show hyperoxia sensitivity in the oxy1 background . Revertants of strain 562, which regain the ability to synthesize melanin by mutation at suppressor sites unlinked to oxy2, retain the oxygen sensitivity conferred by their oxy1 and oxy2 defects . These data identify the melanin gene oxy2 as unique in its association of hyperoxia resistance and melanization.

Clin Infect Dis, 1994 Dec, 19(6), 1029 - 33
Estimation of the prevalence of cryptococcal infection among patients infected with the human immunodeficiency virus in New York City; Currie BP et al.; Cryptococcal infections are not reportable illnesses, and there have been limited attempts to estimate their incidence or prevalence . This study estimates the prevalence of cryptococcal disease in New York City in 1991 among human immunodeficiency virus (HIV)-infected patients who were at risk . Numerator data were generated by surveying all hospitals in New York City to determine the number of patients with cultures positive for Cryptococcus neoformans as well as the number of patients with positive cryptococcal latex agglutination tests in 1991; 517 culture-positive patients were identified, and 1,277 patients were estimated to have a positive cryptococcal latex antigen test . Of these cases, 96% were estimated to be related to infection with HIV . Denominator data were generated via an active surveillance program of the New York City Department of Health . The annual prevalence of cryptococcosis among HIV-infected patients at risk in New York City is estimated to be 6.1%-8.5%.

Kansenshogaku Zasshi, 1994 Dec, 68(12), 1512 - 7
Epidemiology studies of clinical isolates of Cryptococcus neoformans of Japan by restriction fragment length polymorphism; Kohno S et al.; Previous epidemiological studies of Cryptococcus neoformans infection in Japan showed that only C . neoformans var . neoformans is present and serotype A is the most common with frequencies in excess of 95% . A DNA fingerprinting method, using a genomic DNA probe (UT-4p), has become available recently which discriminates between individual isolates in a population that are morphologically and serologically indistinguishable . Fifty-two serotype A isolates of C . neoformans were obtained from three different institutions (in Nagasaki, Chiba, and Tokyo) in Japan . Only two of these strains were isolated from AIDS patients and one from pigeon excreta . Of the nine reported finger-printing patterns in serotype A, only three types (IV, V and VII) were observed in Japanese isolates . Pattern IV was almost exclusively observed in Nagasaki isolates (21/22) with only one of pattern VII . In Chiba, however, patterns VII and IV appeared to be equally distributed . In Tokyo, patterns IV and V (which included two isolates from AIDS patients) were observed at similar frequencies . Restriction fragment length polymorphism analysis of four isolates of serotype AD showed a typical serotype A pattern which also contained a serotype D-specific band . This finding suggests the independence of serotype AD . These data could enhance the survey of the epidemiology of cryptococcosis.

Kansenshogaku Zasshi, 1994 Dec, 68(12), 1465 - 71
{Detection of Candida albicans by nested PCR}; Muramatsu H; A nested PCR assay was developed for the diagnosis of Candida albicans infection . A segment of the C . albicans beta-tubulin gene was amplified in this assay that was sensitive with the detection limit of 10 fg DNA of C . albicans . This assay was found to be specific by obtaining the negative results with 13 organisms (5 other Candida, 2 Cryptococcus, 3 Aspergillus, Escherichia coli and others) . Cerebrospinal fluid of a patient with C . albicans meningitis was analyzed and was found to be positive . These results suggest that this assay can be clinically useful because of its high sensitivity, specificity and rapidity.

Nihon Kyobu Shikkan Gakkai Zasshi, 1994 Dec, 32(12), 1149 - 58
{Lung pathology of cryptococcosis}; Tamura A et al.; To elucidate the relationship between the clinical manifestations and pathologic findings of the lung in patients with cryptococcosis, we reviewed 14 autopsied cases of cryptococcosis . Five patients had pulmonary cryptococcosis and 9 had disseminated cryptococcosis . Patients with pulmonary cryptococcosis showed granulomatous reactions of the lung, such as fibrocaseous cryptococcoma (n = 2), discrete granuloma (n = 2), and granulomatous pneumonia (n = 1) . Patients with disseminated cryptococcosis showed intracapillary/interstitial involvement (n = 2), mucoid pneumonia (n = 3), histiocytic pneumonia (n = 1), and granulomatous pneumonia (n = 3) . There was a distinct difference between pulmonary cryptococcosis and disseminated cryptococcosis in lung pathology . Intracapillary/interstitial involvement and mucoid pneumonia were fatal because of extensive hematogeneous dissemination to other organs . Hilar lymph node involvement of cryptococcosis was found in all of the nine patients with disseminated cryptococcosis and in one of the five patients with pulmonary cryptococcosis . Pleural involvement of cryptococcosis was found in six of the nine patients with disseminated cryptococcosis . We conclude that the clinical manifestations of cryptococcosis are closely associated with the variety of lung pathology of cryptococcosis . Clinicians should understand the morphologic features to cope with patients with cryptococcosis.

Planta Med, 1994 Dec, 60(6), 546 - 9
In vitro synergism of concentrated Allium sativum extract and amphotericin B against Cryptococcus neoformans; Davis LE et al.; Allium sativum (garlic) derived preparations are used alone or with amphotericin B in Asia to treat human systemic fungal infections and cryptococcal meningitis . To evaluate the scientific merit of using allicin-derived compounds as an anti-fungal drug, we prepared a concentrated A . sativum extract that contained 34% allicin, 44% total thiosulfinates, and 20% vinyldithiins . We found that the concentrated extract possessed potent in vitro fungistatic and fungicidal activity against 3 different isolates of Cryptococcus neoformans . The minimum inhibitory concentration of the concentrated garlic extract against 1 x 10(5) organisms of C . neoformans ranged from 6 to 12 micrograms/ml . In addition, in vitro synergistic fungistatic activity with amphotericin B was demonstrated against all isolates of C . neoformans . This study lends laboratory support for the treatment of cryptococcal infections with concentrated garlic extracts.

Am J Clin Pathol, 1994 Dec, 102(6), 741 - 5
Improved detection of Cryptococcus neoformans in the BACTEC NR 660 blood culture system; Prevost-Smith E et al.; To determine the impact of continuous agitation versus 24 hours agitation on the growth of Cryptococcus neoformans in the BACTEC NR 660 blood culture system, the authors compared recovery and detection time for 50 clinical isolates in Peds Plus, 26 Plus, and Fungal Medium bottles in paired simulated blood cultures . After 144 hours of continuous agitation, the Peds Plus bottle detected 96% of the isolates in an average of 82.5 hours, the 26 Plus bottle detected 96% in 79.5 hours, and the Fungal Medium detected 98% in 81.8 hours . For the bottles that were agitated only for the first 24 hours and incubated motionless for 120 hours (as recommended by the manufacturer), the Fungal Medium detected 82% of the isolates in 100.7 hours . However, the Peds Plus and 26 Plus bottles each detected only 38% of the isolates in an average of 112.4 hours and 109.9 hours, respectively . These results indicate that continuous agitation of BACTEC blood culture bottles for the full incubation time significantly improves (P < or = .0001) the detection and recovery of C neoformans.

Zhonghua Nei Ke Za Zhi, 1994 Dec, 33(12), 806 - 8
{Etiological features and abnormal cerebrospinal fluid findings in 101 patients with suspected intracranial infections}; Deng GH et al.; 101 patients (44 males, 57 females) with suspected intracranial infections were admitted to PUMC Hospital from 1988 to 1993 . Their age ranged from 16 to 65 years (mean 29) . Based on etiological categories, viral meningitis or encephalitis was diagnosed in 37.6% of the patients, purulent meningitis in 20.8%, tuberculous meningitis in 19.8%, cryptococcal meningitis in 5.9%, cerebral cysticercosis in 5.9%, infections of unknown etiology in 5.0%, and noninfectious diseases in 4.0% . During hospitalization, the mortality rate for cryptococcal, tuberculous and purulent meningitis was 33.3%, 20.0% and 14.3% respectively . This study also showed that cerebrospinal fluid examination was helpful for etiological analysis or differential diagnosis of intracranial infections.

Mycopathologia, 1994 Dec, 128(3), 151 - 3
Antifungal properties of essential oils and their main components upon Cryptococcus neoformans; Viollon C et al.; Cryptococcus neoformans opportunistic fungus met in the last phasis of AIDS is inhibited in vitro by several essential oils on natural volatile compounds . The minimal inhibitory concentration may reach 100 microliters/l and minimal fungicidal concentration 200 microliters/l with Palmarosa or Cinnamon oils . Among phenolic compounds, thymol and carvacrol are most fungitoxic . Terpenoids, citral, geraniol, and citronellol show best activities.

Mycopathologia, 1994 Dec, 128(3), 143 - 50
Extracellular proteolytic activity of Cryptococcus neoformans; Aoki S et al.; Eight strains of Cryptococcus neoformans var . neoformans isolated from AIDS patients in the Infectious Disease Institute, University of Turin, Italy, were examined for growth and extracellular proteolytic activity in culture with solid and liquid media . All of the strains grew well on Yeast Carbon Base (YCB) agar medium supplemented with both 0.1% (w/v) bovine serum albumin (BSA) and 0.01% (w/v) polypeptone (Pp), and produced a clear proteolytic zone around their colonies, whereas they exhibited less growth and proteolytic activity on YCB medium supplemented with BSA alone . Strain #8 with a strong proteolytic activity was cultured in three different liquid media . Its growth was limited in YCB medium supplemented with 0.1% BSA, but was moderate in that with 0.01% Pp . Enhanced growth was supported by the addition of both BSA and Pp to the YCB medium . The relative value of the final cellular yields obtained with the above YCB-0.1% BSA, YCB-0.01% Pp and YCB-0.1% BSA-0.01% Pp media was approximately 1:10:20 . In the culture with YCB medium containing both BSA and Pp, a rapid decrease in the amount of BSA was demonstrated by a spectrophotometric assay and gel electrophoresis of the culture supernatant after the log-to-stationary phase . The proteolytic activity in the culture supernatant became detectable after the log phase when tested with skim milk agarose plates . These results allowed us to conclude that Cr . neoformans var . neoformans is able to secrete protease and to utilize protein as a source of nitrogen.

J Med Vet Mycol, 1994 Dec, 32(6), 405 - 14
Biochemical basis for the killing of Cryptococcus neoformans by rat peritoneal cells; Rossi GR et al.; The biochemical basis of peritoneal cell cytotoxicity for Cryptococcus neoformans was studied by measuring the killing of the yeast by peritoneal resident cells and peritoneal exudate cells obtained from normal and proteose-peptone-injected animals, respectively . Both cell populations killed C . neoformans to an equivalent extent after 3 h incubation . Exudate cells showed anti-cryptococcal activity from the first hour of incubation, while no killing was observed with resident cells before 3 h . Both cell populations triggered a respiratory burst in response to opsonized C . neoformans as indicated by the fact that killing of the yeast was inhibited by scavengers of reactive oxygen intermediates (ROI) . C . neoformans susceptibility to H2O2 and hydroxyl radicals in cell-free systems is demonstrated by incubating a yeast suspension with different concentrations of H2O2 and Fenton's reagents, respectively . These results suggest that oxygen metabolites play an active role in C . neoformans killing.

Hybridoma, 1994 Dec, 13(6), 531 - 5
Simultaneous expression of kappa and lambda light chains in a murine IgG3 anti-Cryptococcus neoformans hybridoma cell line; Spira G et al.; Allelic exclusion normally results in the expression of only one light and one heavy chain gene . However, some hybridomas have been reported to express two different heavy chain genes . Here we report that the IgG3 hybridoma 4H3.C8B expresses both kappa and lambda light chains . 4H3.C8B was originally recovered by screening for antibody binding to Cryptococcus neoformans polysaccharide antigen and characterized as gamma 3 lambda . The gamma 3 lambda but not the gamma 3 kappa binds to polysaccharide antigen . Some of the antibody molecules were heterodimers composed of both lambda and kappa . IgG1 and IgG2b isotype switch variants were identified and isolated by the technique of sib selection, using the ELISA spot assay . Like the parent IgG3 line, the switch variants continued to express both kappa and lambda light chains but only the lambda-containing antibodies bound to the antigen . Our experience suggests that hybridomas recovered by assays that are antigen dependent should also be tested for the expression of other isotypes and light chains in a non-antigen-binding immunoassay.

J Antimicrob Chemother, 1994 Dec, 34(6), 1051 - 8
Synergic inhibitory activity of amphotericin-B and gamma interferon against intracellular Cryptococcus neoformans in murine macrophages; Herrmann JL et al.; Cryptococcus neoformans is responsible for pulmonary and meningal infections in HIV patients . The lack of effective cellular cooperation caused by the low level of CD4+ cells, and the resistance of C . neoformans to phagocytosis allows growth and persistence of the yeast in the host . We describe here an in-vitro model of intracellular replication of C . neoformans inside J774-A.1 macrophages, and the determination of the intracellular antifungal activity of amphotericin B and fluconazole alone or in association with IFN-gamma . The maximum inhibitory effect was observed with one MIC of amphotericin B and 100 or 1000 IU/mL of IFN-gamma . amphotericin B alone (at 1 x MIC), or either 1 x or 50 x MIC of fluconazole in normal or IFN-gamma activated macrophages, did not eradicate the ingested yeast . A potential underlying mechanism of the synergy of amphotericin B in IFN-gamma primed macrophages was investigated by measurement of nitrite level and by use of the NO synthase competitive inhibitor, NG-monomethyl L-arginine (NMMA) . One MIC of amphotericin B was able to activate the synthesis of nitrogen reactive intermediates in IFN gamma-primed macrophages . NMMA treated infected macrophages responded less well to IFN-gamma priming, resulting in a moderate inhibition in subsequent amphotericin B exposure.

Clin Investig, 1994 Dec, 72(12), 1020 - 6
Elevation of intracranial pressure in acute AIDS-related cryptococcal meningitis; Malessa R et al.; Prior to the AIDS-era, elevation of intracranial pressure was known to be a typical complication of cryptococcal meningitis associated with an increased risk of early death . In AIDS-patients, however, the prevalence and clinical significance of this complication are as yet unclear . We analysed clinical features and courses, CSF findings, serological results and neuroimaging scans in acute cryptococcal meningitis in eight patients with AIDS . Five showed symptoms and signs compatible with raised intracranial pressure, which was life-threatening in one and the most probable cause of death in another . Serial monitoring of intracranial pressure together with repeated CSF analysis revealed that severe intracranial pressure elevation in AIDS related cryptococcal meningitis can occur in spite of effective antimycotic treatment, does not depend on an increased CSF/serum osmolality ratio or CSF overproduction and can be associated with normal cranial computed tomography and magnetic resonance imaging findings . Our data support the hypothesis that CSF reabsorption failure plays the crucial role in the pathophysiological mechanism . External lumbar drainage may be of benefit in selected cases of acute AIDS related cryptococcal meningitis with persisting life threatening elevation in intracranial pressure and normal computed tomogram.

Acta Neurol (Napoli), 1994 Dec, 16(5-6), 288 - 90
False positive of ADA determination in cerebrospinal fluid; Egido JA et al.; The elevation of ADA in CSF is useful as a diagnostic means for detecting tuberculous meningitis, and in other etiologies such as lymphoma, neurosarcoidosis, fulminant bacterial meningitis, cryptococcal meningitis, neurobrucellosis and AIDS . We report an increase of ADA in CSF in association with SHA . In our case the total activity of ADA was the same as that obtained in serum, which can be interpreted among the false positives of the determination.

Cent Eur J Public Health, 1994 Dec, 2(2), 100 - 2
Mycobacterial infections in patients with AIDS in a low HIV prevalence area; Stankova M et al.; The Czech Republic is characterized here as both a low HIV prevalence area (1.64 registered positivity per 10(5) population and 45 AIDS patients notified in the 1986-93 period) and a low tuberculosis prevalence area (mortality rate 0.8, incidence of bacillary pulmonary cases 11.3 per 10(5) population and risk of infection 0.04 in 1990) . From 1986 to 1993 a total of 10 cases of mycobacterial infections complicating AIDS or ARC disease were registered in the Czech Republic in 9 male patients aged from 29 to 55, 8 homosexuals, and one woman aged 48 . Classical pulmonary tuberculosis caused by M . tuberculosis was diagnosed in one male patient and was controlled by antituberculosis chemotherapy . The remaining mycobacterial infections were caused by the following opportunistic mycobacterial pathogens . (a) M . avium in five individuals, four of them died of a disseminated disease; (b) M . kansasii--in two patients, one died of a disseminated infection; (c) M . xenopi--involved in a fatal generalized CMV, and cryptococcal and mycobacterial infection; (d) M . fortuitum caused a generalized disease in a case of exhaustive multifocal encephalopathy . Authors conclude that under conditions of low prevalence of both HIV and tuberculosis infection the risk to AIDS patients of contracting classical tuberculosis is low . A relatively frequent occurrence of non-tuberculosis mycobacterial disease in AIDS patients afflicted with the impaired immunity is explained by transmission of opportunistic mycobacteria from the environment.

Eur J Epidemiol, 1994 Dec, 10(6), 773 - 4
Chronic cryptococcal meningitis in an intravenous drug addict without evidence of infection by HIV-1,2 in southern Italy; Monno L et al.; Before the emergence of AIDS, extrapulmonary cryptococcosis was very rare . By contrast, meningeal cryptococcosis is a very common opportunistic infection in AIDS patients . We report an intravenous drug addict with cryptococcal meningitis, who was not infected with HIV and had no apparent predisposing conditions . This case, as those elsewhere described, supports the potential existence of viral agents, other than HIV-1,2 capable of encouraging the occurrence of unusual infections as have emerged during the AIDS pandemic.

Ann Intern Med, 1994 Nov 15, 121(10), 769 - 85
Neurologic manifestations of HIV infection; Simpson DM et al.; PURPOSE: To review the clinical features, pathogenetic mechanisms, and management of neurologic manifestations of human immunodeficiency virus (HIV) infection . DATA SOURCES: Studies published from 1983 to 1994 identified by MEDLINE literature search; Centers for Disease Control and Prevention reports; recent communications and abstracts; and authors' published and unpublished data . STUDY SELECTION: We selected studies that described the clinical characteristics of neurologic disorders in the acquired immunodeficiency syndrome (AIDS), basic science studies addressing the mechanisms of direct or indirect neurologic damage in HIV infection, and clinical trials investigating the effects of therapeutic agents on the neurologic complications of AIDS . DATA EXTRACTION: We evaluated information and data on epidemiologic characteristics, clinical manifestations, pathogenetic mechanisms, and therapy for neurologic complications of HIV disease and outlined a practical approach to assess and manage these disorders . DATA SYNTHESIS: In the past decade, basic and clinical studies have provided considerable information about neurologic manifestations of AIDS . Dementia is the most important "primary" neurologic complication of HIV infection . Focal lesions of the central nervous system include cerebral toxoplasmosis, lymphoma, and progressive multifocal leukoencephalopathy . Other opportunistic infections include cytomegalovirus encephalitis, cryptococcal meningitis, and neurosyphilis . Various peripheral neuropathies and myopathies may occur in association with HIV infection or as toxic effects of antiretroviral agents . CONCLUSIONS: The prevalence of neurologic complications associated with HIV disease will increase as more effective therapies allow persons with AIDS to live longer . Early recognition and treatment of these disorders substantially affect patients' quality of life and survival.

Clin Diagn Lab Immunol, 1994 Nov, 1(6), 737 - 40
Prevalence in Cryptococcus neoformans strains of a polysaccharide epitope which can elicit protective antibodies; Cleare W et al.; Monoclonal antibody (MAb) 2H1 binds to an epitope in the capsule of Cryptococcus neoformans that can elicit protective antibodies . The binding of MAb 2H1 to C . neoformans strains was studied by agglutination, immunofluorescence, and phagocytosis assays . The MAb 2H1 epitope was present in all 21 isolates studied, including those recovered from patients with recurrent infections.

Br J Rheumatol, 1994 Nov, 33(11), 1085 - 6
Cryptococcal spondylitis: solitary infective bone lesions are not always tuberculous; Glynn MJ et al.; Tuberculous spondylitis is a well-recognized cause of back pain and vertebral collapse due to infection and with must not be overlooked even if it is not the most likely diagnosis . If a patient, particularly one of Asian origin, were to present with a solitary destructive bone lesion, without evidence of myeloma or other malignancy, a trial of anti-tuberculous chemotherapy would be one therapeutic approach, even if there was no evidence of tuberculosis elsewhere . However, failure to biopsy the bone lesion and undertake the appropriate microbiology could lead to other important diagnoses being missed . This is illustrated by the case which we report below.

Am J Kidney Dis, 1994 Nov, 24(5), 864 - 7
Cryptococcal infection of a prosthetic dialysis fistula; Braun DK et al.; Fungal infections of prosthetic dialysis fistulae are rare . We report the first case of infection of a polytetrafluoroethylene dialysis access graft with the yeast Cryptococcus neoformans . Therapy with antifungal agents alone failed to cure the infection and significant improvement was observed only when all prosthetic material was surgically removed . This case emphasizes the potential for fungal infection of prosthetic dialysis fistulae and the importance of removal of intravascular foreign material in conjunction with antifungal therapy for treatment of fungal prosthetic graft infections.

Radiology, 1994 Nov, 193(2), 389 - 92
Pulmonary mycobacterial infections in AIDS: characteristic pattern of thallium and gallium scan mismatch; Lee VW et al.; PURPOSE: To evaluate the diagnostic specificity of thallium and gallium scan mismatch as a sign of mycobacterial infection in immunodeficient patients . MATERIALS AND METHODS: Thallium and gallium scans obtained in 56 immunodeficient patients between January 1989 and March 1994 were retrospectively reviewed, with special attention to the final diagnoses in all patients with thallium-gallium scan mismatch compared with those whose scans showed other scintigraphic patterns . RESULTS: Fourteen patients had focal gallium uptake, but no thallium uptake, in the mediastinum and hilar nodes (thallium-gallium mismatch) . Twelve of the 14 had culture-proved mycobacterial infections; one had cryptococcal infection; and in one, the diagnosis was not established . Thirty-seven of the remaining 42 patients who had different scintigraphic patterns on thallium-gallium scans had other complications of acquired immunodeficiency syndrome such as Kaposi sarcoma, non-Hodgkin lymphoma, and bacterial pneumonia . The diagnosis in five of the 42 patients was not known because follow-up data were incomplete . CONCLUSION: The thallium-gallium mismatch pattern in immunodeficient patients is specific for mycobacterial infection.

Mayo Clin Proc, 1994 Nov, 69(11), 1111 - 7
Therapy for fungal infections; Sarosi GA et al.; In the past, few pharmacologic agents were available for management of fungal disease . After the early introduction of amphotericin B and miconazole, the more recent advent of several new antifungal agents, including ketoconazole, fluconazole, and itraconazole has expanded the options for treatment of fungal infections . The dramatic increase in number of immunocompromised patients--both those with acquired immunodeficiency syndrome (AIDS) and those with immunosuppression for other reasons, such as organ transplantation--emphasizes the importance of therapeutic strategies for combating systemic mycoses . In this article, we review our personal recommendations for treating histoplasmosis, blastomycosis, coccidioidomycosis, and cryptococcosis, along with other less common fungal infections, and discuss the efficacy and toxic effects of the various antifungal drugs.

J Infect Dis, 1994 Nov, 170(5), 1331 - 4
In vivo activity of interferon-gamma in combination with amphotericin B in the treatment of experimental cryptococcosis; Joly V et al.; The effect of recombinant interferon-gamma (rIFN-gamma) on Cryptococcus neoformans infection was investigated in vivo . BALB/c mice were injected intravenously with 2 x 10(6) C . neoformans . rIFN-gamma alone (10 micrograms intraperitoneally 18 h before, at, 24 h after infection) significantly increased the survival and decreased the colony-forming unit counts in the lungs compared with untreated mice . rIFN-gamma association significantly enhanced the effect of a single dose of amphotericin B (0.25 mg/kg 24 h after infection) to prolong mouse survival and to reduce colony counts in the brain . Tumor necrosis factor-alpha levels, measured in spleen 3, 6, and 24 h after infection, were not increased by rIFN-gamma . These results suggest that exogenous rIFN-gamma might improve the effect of antifungal therapy during cryptococcosis.

Hum Pathol, 1994 Nov, 25(11), 1123 - 40
Gastrointestinal disease in the immunocompromised patient; Rotterdam H et al.; Gastrointestinal (GI) disease is frequent in all types of immunocompromised patients but occurs with greatest frequency in patients with acquired immunodeficiency syndrome (AIDS) . Thus, much of this review deals with human immunodeficiency virus (HIV)-related GI diseases . Gastrointestinal diseases in other immunocompromised patients are compared with those in patients with AIDS . Conditions unique to transplant recipients, such as graft-versus-host disease (GVHD) and posttransplant lymphoproliferative disorders (PTLDs), are discussed separately . We have divided these GI diseases into four main categories: (1) HIV-related inflammatory conditions other than opportunistic infections (HIV-related enteropathy, proctocolitis, and CD8 lymphocytosis); (2) inflammatory conditions unrelated to HIV or opportunistic infections (neutropenic enterocolitis, regional enteritislike enteropathy, and GVHD); (3) opportunistic infections (illnesses caused by herpesvirus, cytomegalovirus, and miscellaneous other viruses; Mycobacterium, Candida, Histoplasma, Cryptococcus, Cryptosporidium, Microsporida, Isospora, Leishmania, Toxoplasma and Strongyloides organisms as well as Pneumocystitis carinii; and (4) neoplasias (Kaposi's sarcoma {KS}, AIDS-related non-Hodgkin's lymphoma {NHL}, HIV-related Hodgkin's disease {HD}, PTLDs, and miscellaneous neoplasms) . The prevalence, pathogenesis, clinical manifestations, gross pathological findings, and microscopic features of each disease entity are discussed.

Clin Exp Immunol, 1994 Nov, 98(2), 217 - 23
Encapsulation of Cryptococcus neoformans regulates fungicidal activity and the antigen presentation process in human alveolar macrophages; Vecchiarelli A et al.; Our previous studies have shown that unstimulated alveolar macrophages (AM) play a predominant role as antigen-presenting cells in Cryptococcus neoformans infections, while the function as effector cells seems to be of minor relevance . The present study focuses on the role of encapsulation of C . neoformans on fungicidal activity and the antigen presentation process of AM . Fungicidal activity in unstimulated AM occurs to a higher degree when the acapsular strain is employed, but this is impaired compared with other natural effectors, such as peripheral blood monocytes (PBM) and polymorphonuclear (PMN) cells . Cryptococcus-laden AM also induce a higher proliferative response in autologous CD4+ lymphocytes when the acapsular strain is used compared with encapsulated yeast . The enhanced blastogenic response is, in part, ascribed to an augmented IL-2 production by T cells . In addition, higher levels of interferon-gamma (IFN-gamma), but not IL-4, are produced by the responding T cells, when the acapsular strain is used compared with the encapsulated yeast . Moreover, IFN-gamma is able to induce fungicidal activity in AM against the encapsulated yeast and augments killing activity of the acapsular strain . This phenomenon is not mediated by nitric oxide production, but is correlated with an enhancement of fungicidal activity of cytoplasmic cationic proteases . We speculate that encapsulation of C . neoformans could down-regulate the development of the immune response mediated by Cryptococcus-laden AM at lung level.

Infect Immun, 1994 Nov, 62(11), 4755 - 61
Pathogenesis of pulmonary Cryptococcus neoformans infection in the rat; Goldman D et al.; The pathogenesis of Cryptococcus neoformans pulmonary infection in the rat was studied after intratracheal inoculation . Lungs were examined at various times following infection for histopathology in conjunction with macrophage markers, proliferating cell nuclear antigen (PCNA), and capsular glucuronoxylomannan (GXM) antigen . Serum GXM, immunoglobulin M (IgM) and IgG titers and organ fungal burden were compared with pathological findings . C . neoformans organisms were in the lung parenchyma 2 h postinoculation, and GXM antigen was present in surrounding tissues shortly thereafter . Extrapulmonary dissemination occurred early in infection . Two phases of host cellular inflammatory response were discernible: early local macrophage recruitment at 2 to 4 days followed by granulomatous inflammation, which reached maximum intensity 14 days after infection . The granulomatous phase was preceded by lymphocyte influx with macrophage proliferation and maturation into epithelioid histiocytes; this was paralleled by a shift of yeasts from extracellular to intracellular spaces . Tissue IgG deposits, serum IgG to GXM, and localization of tissue GXM immunoreactivity to epithelioid cells were noted at 2 to 4 weeks . A 10-fold decrease in lung fungal burden occurred 25 days postinfection and was associated with resolving granulomas, fewer proliferating cells, and decreased tissue GXM . The present study demonstrates that (i) C . neoformans penetrates the lung parenchyma shortly after infection; (ii) immunocompetent rats control pulmonary cryptococcosis efficiently, with minimal extrapulmonary dissemination and low levels of serum GXM; and (iii) macrophage activation is likely to play a crucial role in limiting C . neoformans infection in the rat lung.

Clin Infect Dis, 1994 Nov, 19(5), 951 - 3
Management of injuries caused by Cryptococcus neoformans--contaminated needles; Casadevall A et al.; This report describes four skin-puncture accidents with needles that were heavily contaminated with Cryptococcus neoformans . In one accident, delayed administration of antifungal drugs resulted in a granuloma of the finger . In the other three accidents, no skin infection followed immediate prophylaxis with oral fluconazole . Our experience suggests that early therapy with fluconazole is a reasonable means of managing skin injuries caused by instruments contaminated with viable C . neoformans.

Antimicrob Agents Chemother, 1994 Nov, 38(11), 2648 - 50
Growth of Cryptococcus neoformans in presence of L-dopa decreases its susceptibility to amphotericin B; Wang Y et al.; Cryptococcus neoformans grown with L-dopa was melanized and was less susceptible to amphotericin B . The results suggest that in vivo and in vitro susceptibilities to amphotericin B may differ.

Cutis, 1994 Nov, 54(5), 343 - 7
Review of the morphological variations in cutaneous cryptococcosis with a new case resembling varicella; Yantsos VA et al.; A 26-year-old black man with acquired immune deficiency syndrome and disseminated cryptococcosis presented with multiple small white vesiculopustular skin lesions on the face, trunk, and upper extremities mimicking varicella . To our knowledge, this is a novel presentation of cutaneous cryptococcal infection . A review of the morphologic variations seen in cutaneous Cryptococcus infections in patients with and without acquired immune deficiency syndrome is also presented.

Kansenshogaku Zasshi, 1994 Nov, 68(11), 1417 - 20
{A case report: cryptococcal meningitis and fluconazole therapy}; Takeda S et al.; An 18-year-old female was given prednisolone and azathioprine for treatment of systemic lups erythematosus . She was admitted to Fukuoka University Hospital because of headache and vomiting . Examinations revealed she was suffering from cryptococcal meningitis . Fluconazole (FLCZ) 400 mg a day was administrated for therapy . Her general condition improved and the serum level of cryptococcal antigen decreased one month after therapy . This therapy resulted in abatement of subjected symptoms and sterilization of the cerebral spinal fluid . This case suggested that therapy with FLCZ alone is useful for patients with cryptococcal meningitis, therefore the standard therapy with amphotericin B (AMPH) or the combination.

Mycopathologia, 1994 Nov, 128(2), 85 - 9
Effect of amphotericin B on the lipids of five different strains of Cryptococcus neoformans; Franzot SP et al.; Cells of five strains of Cryptococcus neoformans were obtained for partial analysis of lipid composition . Quantitative analysis of lipids and sterols were completed, as well as qualitative analysis of sterols by thin-layer chromatography and by the ultraviolet spectra . Such determinations were made on cells cultured in the absence and presence of amphotericin B at sub-MIC (minimal inhibitory concentration) levels . Marked alterations of the lipid and sterol contents were observed in the amphotericin B-treated cells . Moreover, ergosterol disappeared in these antibiotic-exposed cells . It is concluded that amphotericin B altered the lipid profiles, especially sterols of C . neoformans.

Mycoses, 1994 Nov-Dec, 37(11-12), 411 - 6
Turbidimetric and visual criteria for in vitro susceptibility testing of Cryptococcus neoformans clinical isolates; Del Poeta M et al.; The drug concentration which inhibited 50% of growth (IC50), the lowest drug concentration at which growth was less than 30% of that in a positive control well (IC30), the visual minimal inhibitory concentration (MIC visual), were applied to study the effects of fluconazole, itraconazole, amphotericin B and flucytosine against 27 isolates of Cryptococcus neoformans by a broth microdilution technique . When the recommendations established by NCCLS Subcommittee on Antifungal Susceptibility Test were applied for the visual reading of the microplates, the results were comparable with those obtained by the turbidimetric method . No statistically significant differences between MIC visual and IC30 readings were observed with the azoles . There were, however, differences with amphotericin B and flucytosine . In absolute terms MICs of amphotericin B and flucytosine showed higher values than IC30s and IC50s.

Rev Inst Med Trop Sao Paulo, 1994 Nov-Dec, 36(6), 551 - 4
Flucytosine+fluconazole association in the treatment of a murine experimental model of cryptococcosis; Bava AJ et al.; The efficacy of flucytosine (5-FC) and fluconazole (FLU) association in the treatment of a murine experimental model of cryptococcosis, was evaluated . Seven groups of 10 Balb C mice each, were intraperitoneally inoculated with 10(7) cells of Cryptococcus neoformans . Six groups were allocated to receive 5-FC (300 mg/kg) and FLU (16 mg/kg), either combined and individually, by daily gavage beginning 5 days after the infection, for 2 and 4 weeks . One group received distilled water and was used as control . The evaluation of treatments was based on: survival time; macroscopic examination of brain, lungs, liver and spleen at autopsy; presence of capsulated yeasts in microscopic examination of wet preparations of these organs and cultures of brain homogenate . 5-FC and FLU, individually or combined, significantly prolonged the survival time of the treated animals with respect to the control group (p < 0.01) . Animals treated for 4 weeks survived significantly longer than those treated for 2 weeks (p < 0.01) . No significant differences between the animals treated with 5-FC and FLU combined or separately were observed in the survival time and morphological parameters . The association of 5-FC and FLU does not seem to be more effective than 5-FC or FLU alone, in the treatment of this experimental model of cryptococcosis.

Rev Prat, 1994 Oct 15, 44(16), 2187 - 94
{Cerebro-meningeal infections in patients with human immunodeficiency virus infections}; Struillou L et al.; Opportunistic infections of the central nervous system, frequent in AIDS, present essentially in 4 clinical pictures: brain mass lesion(s), meningitis, diffuse encephalitis or prolonged fever . Toxoplasmosis is by far the most frequent cause of brain mass lesion . Therefore, for patients presenting with a brain mass lesion it is recommended to start presumptive antitoxoplasmic therapy with the combination of pyrimethamine and sulfadiazine . Other etiologies (lymphoma and progressive multifocal leukoencephalopathy) should be considered only after failure of this treatment . The other infectious processes are much more uncommon (cryptococcoma, tuberculoma, Candida, Nocardia abscesses) . In case of meningitis, cryptococcosis must be searched for, in addition to classic causes of meningitis . Diffuse febrile encephalitis should lead to consider presumptive antitoxoplasmic therapy . Finally, prolonged fever can be the only expression of cerebral toxoplasmosis or cryptococcal meningitis.

Can J Microbiol, 1994 Oct, 40(10), 888 - 92
Cryptococcus neoformans infection can elicit protective antibodies in mice; Mukherjee J et al.; An IgG1 monoclonal antibody generated from a mouse infected with Cryptococcus neoformans modified the course of intravenous cryptococcal infection in A/J mice by prolonging survival and reducing lung fungal burden, brain mass, and serum polysaccharide levels . The results demonstrate that C . neoformans infection can elicit useful antibodies.

Appl Environ Microbiol, 1994 Oct, 60(10), 3864 - 6
Decreased susceptibility of melanized Cryptococcus neoformans to UV light; Wang Y et al.; Melanized Cryptococcus neoformans cells were less susceptible than nonmelanized cells to the fungicidal effects of UV light . Phenoloxidase-catalyzed production of melanin-like pigments may serve to protect the fungus against ionizing radiation.

Cancer Nurs, 1994 Oct, 17(5), 411 - 7
Fungal infections associated with malignancies, treatments, and AIDS; Benedict S et al.; Severe fungal infections have become increasingly common over the past 10 years, largely due to the greater number of immunocompromised patients, such as those infected with HIV and those undergoing immunosuppressive therapy for malignancies . Between 60% and 80% of people with AIDS, for example, develop at least one fungal infection . Other predisposing factors for these infections include mechanical defects such as indwelling catheters, surgery, and burns . Candidiasis, aspergillosis, cryptococcoses, coccidioidomycosis, and histoplasmosis are among the fungal infections most commonly encountered in the clinical setting . Diagnosis is often elusive and treatment difficult . Amphotericin B has been the standard therapy for most life-threatening fungal infections for almost three decades but has significant drawbacks, including severe adverse reactions . Other systemic antifungal agents have proved useful in certain situations . Fluconazole, a new broad-spectrum agent, has shown particular promise in the treatment of candidiasis and cryptococcal meningitis.

Neurology, 1994 Oct, 44(10), 1892 - 900
Temporal trends in the incidence of HIV-1-related neurologic diseases: Multicenter AIDS Cohort Study, 1985-1992; Bacellar H et al.; OBJECTIVE: To describe temporal trends in the incidence of human immunodeficiency virus (HIV)-related neurologic diseases in the Multicenter AIDS Cohort Study from 1985 to 1992 . METHODS: The incidence rates of six neurologic disorders were examined: toxoplasmosis, cryptococcal meningitis, primary CNS lymphoma, progressive multifocal leukoencephalopathy, HIV dementia, and sensory neuropathy . Poisson modeling was used to test linear trends over time and the effects of progressive immunosuppression, antimicrobial prophylaxis, and antiretroviral drug therapy . RESULTS: There was an upward temporal trend in all incidence rates, except for HIV dementia . Progressive immunosuppression in the cohort explained all calendar trends except for sensory neuropathy, where an increasing temporal trend remained even after adjusting for CD4+ cell count, and for HIV dementia where a slight decline was noted, although the effects were not statistically significant . We noted a protective trend of antimicrobial prophylaxis on toxoplasmosis and cryptococcal meningitis, but, in contrast, use of antiretroviral agents was not protective against HIV dementia . Men receiving didanosine, zalcitabine, or stavudine were more likely to develop sensory neuropathy . CONCLUSION: Despite the earlier and more widespread use of antimicrobial and antiretroviral agents, neurologic conditions still occurred frequently in this cohort, with annual rates above 1.5 per 100 person-years for HIV dementia and sensory neuropathy . Sensory neuropathy seems to be increasing in incidence and HIV dementia declining slightly in this cohort . As the epidemic matures and more people with profound immunosuppression live longer, the overall incidence of HIV-related neurologic diseases can be expected to rise.

J Am Coll Cardiol, 1994 Oct, 24(4), 1018 - 24
Frequency of development of acute global left ventricular dysfunction in human immunodeficiency virus infection; De Castro S et al.; OBJECTIVES . This study evaluated prospectively the frequency, clinical outcome and pathologic findings of acute global left ventricular dysfunction in human immunodeficiency virus (HIV) infection during the various stages of the disease . BACKGROUND . Acute global left ventricular dysfunction in the course of HIV infection is still a poorly defined clinical entity, and little is known about the outcome after the acute onset . METHODS . Between January 1988 and June 1992, 136 HIV-positive (HIV+) patients without clinical, electrocardiographic or echocardiographic evidence of cardiovascular dysfunction on admission were prospectively studied with serial echocardiograms . Patients were assigned to three groups: 1) anti-HIV+ asymptomatic (17 patients, 12.5%); 2) acquired immunodeficiency syndrome (AIDS)-related complex (26 patients, 19.1%); 3) AIDS (93 patients, 68.4%) . RESULTS . During a mean follow-up period of 415 +/- 220 days, seven patients, all in the AIDS subgroup, developed clinical and echocardiographic findings of acute global left ventricular dysfunction; of these, six (85%) died of congestive heart failure . Mean survival time from symptom onset was 41 +/- 13 days . Necropsy findings in five patients revealed acute lymphocytic myocarditis in three, cryptococcal myocarditis in one and interstitial edema and fibrosis in one . In only one patient was left ventricular dysfunction reversible with treatment . CONCLUSIONS . Although infrequent, acute global left ventricular dysfunction is not rare in the course of HIV infection . It seems to occur exclusively during the AIDS stage . Acute global left ventricular dysfunction is often fatal but may be reversible and is mainly associated with the pathologic findings of acute myocarditis.

Histol Histopathol, 1994 Oct, 9(4), 643 - 8
Prostatic sequestration of Cryptococcus neoformans in immunocompromised persons treated for cryptococcal meningoencephalitis; Ndimbie OK et al.; We report a case of a patient with acquired immune deficiency syndrome who was successfully treated for cryptococcal meningoencephalitis with amphotericin B and 5-flucytosine . He died from other sequelae of acquired immune deficiency syndrome two years later . An autopsy revealed prominent cryptococcal prostatitis . Cryptococci were neither found in the central nervous system nor in other anatomic sites . The autopsy files yielded seven other cases of men with a history of cryptococcal meningoencephalitis . The possibility that the prostate sequesters Cryptococcus neoformans thereby contributing to systemic relapse is explored . The qualify as a sequestration, cyptococci must be cultured from the prostate, or from a midstream voided specimen after prostatic massage, and the prostate must be the only focus of infection.

Diagn Microbiol Infect Dis, 1994 Oct, 20(2), 87 - 91
Comparison of fluconazole minimum inhibitory concentrations in three different formulations of RPMI-1640; Espinel-Ingroff A et al.; This study aimed to compare the susceptibilities of fluconazole, obtained in two laboratories, using three RPMI-1640 formulations (manufacturers') and inhibition standards (80%) . A total of 39 selected Candida species (in vitro susceptible and resistant) and Cryptococcus neoformans isolates were tested in each medium by broth macro- and microdilution procedures following the National Committee for Clinical Laboratory Standards proposed reference method (M27-P) . Macrodilution minimum inhibitory concentrations (MIC80%) were the lowest drug concentrations with turbidity (growth) less than or equal to that of the specific 80% inhibition standards (1:5 growth control) . Microdilution MIC-2 were the lowest drug concentrations in which there was prominent decrease in growth . In general, the three formulations of RPMI-1640 medium provided similar MICs for most of the yeasts tested in both laboratories and by each test.

Diagn Microbiol Infect Dis, 1994 Oct, 20(2), 81 - 6
Evaluation of 80% inhibition standards for the determination of fluconazole minimum inhibitory concentrations in three laboratories; Espinel-Ingroff A et al.; The purpose of this study was to evaluate 1:5 growth control dilutions (80% inhibition standards) to determine fluconazole minimum inhibitory concentration (MIC) end points in three laboratories . We tested 39 selected Candida species (in vitro susceptible: fluconazole MIC of < or = 1 microgram/ml, and resistant: fluconazole MIC of > or = 8 micrograms/ml) and Cryptococcus neoformans isolates by broth macro- and microdilution procedures following the National Committee for Clinical Laboratory Standards proposed reference method for yeasts (M27-P) . Macrodilution MIC80% were the lowest drug concentrations with turbidity (growth) less than or equal to that of specific 1:5 dilutions of the growth control . Microdilution MICs-2 were the lowest drug concentrations in which there was prominent decrease of growth . A total of 1608 MICs were evaluated . C . krusei, C . parapsilosis, and C . tropicalis strains had reproducible fluconazole MICs by both tests (24 and 48 h) . Fluconazole MIC80% and MIC-2 end points were consistent at 24 h (with C . albicans) and more variable at 48 h . MICs of C . neoformans were more reproducible at 72 h than at 48 h by both tests . This study suggests that the determination of fluconazole MICs is dependent on the length of incubation and the yeast being tested, and that antifungal testing of the yeasts may be performed by either test.

J Neurol Sci, 1994 Oct, 126(1), 49 - 53
Intrathecal synthesis of interleukin-10 (IL-10) in viral and inflammatory diseases of the central nervous system; Gallo P et al.; The intrathecal synthesis of interleukin 10 (IL-10) was investigated in 120 paired cerebrospinal fluid (CSF) and serum specimens from patients with various inflammatory and non-inflammatory diseases of the central nervous system (CNS) . IL-10 was not demonstrated in the sera, but detectable levels were found in the CSF from: patients with acute viral ("aseptic") meningitis, but only within 48-72 h of symptom onset; human immunodeficiency virus type 1 (HIV)-infected patients with HIV-related encephalitis/leukoencephalopathy or cryptococcal meningitis; a patient with primary B cell lymphoma of the CNS, and a patient with encephalomeningeal sarcoidosis (in whom IL-10 was demonstrated in all CSF collected over a period of 6-months) . In chronic meningeal infections/inflammations, IL-10 seems to be continuously produced within the CSF . Our findings suggest that IL-10, a cytokine which exerts many immunosuppressive actions, may play different immunomodulatory roles in CNS diseases; in particular, its intrathecal synthesis may explain why some infectious and inflammatory meningeal diseases may have slow development and chronic evolution.

J Clin Microbiol, 1994 Oct, 32(10), 2364 - 71
Molecular typing of Cryptococcus neoformans serotype D clinical isolates; Dromer F et al.; Cryptococcus neoformans serotype A is responsible for the majority of cryptococcal infections in AIDS patients . In France, approximately 17% of the patients are infected with serotype D, regardless of their human immunodeficiency virus status . In a retrospective study of 273 patients, we found that serotype D was unevenly distributed in France . We wondered if this was related to the yeast's genetic background . We used karyotyping and DNA fingerprints generated by UT-4p to analyze 40 serotype D clinical isolates . We found an extensive polymorphism, with only two conserved karyotypes from drug-addicted patients living in the same area . Although highly variable, the DNA fingerprints were classified into 10 groups . Four pairs of isolates were identical; three of these pairs were from patients living in the same area, but there was no other correlation with the geographical area . The two isolates with identical karyotypes belonged to the same fingerprint group . Five of the six isolates that made up fingerprint group I were recovered from drug-addicted patients (P < 0.002; chi-square), and all five isolates found in fingerprint group III were from male homosexual patients (P < 0.02) . Finally, five of the seven isolates from patients with cryptococcal pneumonia were classified as fingerprint group V (P < 0.04) . These results suggest that there are possible relationships between characteristics of the isolates and body localization or even risk factors . Results of the present study warrant other studies on isolates of all serotypes and on isolates from clinical and environmental sources.

Recenti Prog Med, 1994 Oct, 85(10), 467 - 70
{Infections in heart transplantations}; Delfino M et al.; Infections are one of the most important problems in heart transplants recipients: they are responsible for half total mortality within one year after surgery and one third of mortality during the following period . Underlying medical illness of the host, lack of specific immunity, prior colonization are conditions that may contribute to infections after surgery: immunosuppression to contrast rejection or due to Cytomegalovirus (CMV) infection are other factors favoring infections . Lung infections are most frequent . During the first month after surgery microorganisms responsible are the same found in cardiosurgery patients, staphylococci and gram negative, and occasionally herpes simplex virus (ESV) reactivated infections occur . From the second to the sixth month most of the CMV and Toxoplasma infections occur, with some Pneumocystis and mycotic events . Both are so frequent that in a seronegative host a specific prophylaxis against CMV and Toxoplasma is regularly recommended . The very late period more than six month after surgery is characterized by common infections seen in any population, that may present in altered or more severe fashion due to immune suppression . Another late event is cryptococcal meningitis.

J Nat Prod, 1994 Oct, 57(10), 1437 - 41
Hamacanthins A and B, new antifungal bis indole alkaloids from the deep-water marine sponge, Hamacantha sp; Gunasekera SP et al.; Hamacanthin A {1} and hamacanthin B {2} are two bioactive dihydropyrazinonediylbis(indole) alkaloids isolated from a new species of deep-water marine sponge, Hamacantha sp . The hamacanthins are growth inhibitors of Candida albicans and Cryptococcus neoformans . Isolation and structure elucidation of 1 and 2 by nmr spectroscopy are described.

Clin Infect Dis, 1994 Oct, 19(4), 741 - 5
Fluconazole combined with flucytosine for treatment of cryptococcal meningitis in patients with AIDS; Larsen RA et al.; Treatment of cryptococcal meningitis with amphotericin B or fluconazole is often unsuccessful; in only 35%-40% of cases do CSF cultures become negative by 10 weeks after initiation of such therapy . We conducted a prospective, open-label clinical trial involving persons with AIDS to determine whether the rate of clinical success would improve when fluconazole (400 mg daily) was combined with flucytosine (150 mg/kg daily) . At the conclusion of 10 weeks of therapy, 75% (95% confidence interval, 58%-87%) of 32 subjects' CSF cultures were negative . The Kaplan-Meier estimate of clinical success at 10 weeks was 63% (95% confidence interval, 48%-82%) . The median time to negativity of the CSF culture was 23 days . Toxic side effects that were sufficiently severe to lead to the withdrawal of flucytosine were observed in nine subjects (28%) . In this pilot study of fluconazole combined with flucytosine, the rate of clinical success at 10 weeks was greater than that previously reported with regard to the use of fluconazole alone or amphotericin B alone.

Ugeskr Laeger, 1994 Sep 19, 156(38), 5532 - 4
{Cryptococcal meningitis in patients without predisposing immunodeficiency}; Jensen T et al.; Cryptococcal meningitis is a chronic or subacute meningeal infection that may have pulmonary or systemic manifestations and is caused by the yeast Cryptococcus neoformans . It has become an increasingly important pathogen in immunocompromised hosts, whereas cryptococcal meningitis is relatively rare in immunocompetent patients . The diagnosis is often delayed because of the sparse and nonspecific symptoms . We present two cases of cryptococcal meningitis in two patients without known predisposing factors . The symptomatology, diagnosis and treatment of the disease are discussed . The two cases illustrate that Cryptococcus neoformans should be considered in patients with cerebral symptoms and fever . The disease is potentially curable and early diagnosis with specific treatment are important prognostic factors.

FEMS Microbiol Lett, 1994 Sep 15, 122(1-2), 39 - 42
Resistance to amphotericin B associated with defective sterol delta 8-->7 isomerase in a Cryptococcus neoformans strain from an AIDS patient; Kelly SL et al.; Two Cryptococcus neoformans strains isolated from an AIDS patient were investigated, a pretreatment isolate (CN1) and a second isolate (CN3) following failure of fluconazole and amphotericin B treatment . No difference in fluconazole sensitivity, but relative resistance to amphotericin B was observed for CN3 . The sterol composition of CN3 indicated a defect in sterol delta 8-->7 isomerase in this strain and depletion of ergosterol, the major sterol of the CN1.

Biochem J, 1994 Sep 1, 302 ( Pt 2), 429 - 36
Specificity of the thioester-containing reactive site of human C3 and its significance to complement activation; Sahu A et al.; The specificity of the thioester-containing site in three plasma proteins is regulated by elements of their protein structures other than the thioester bond itself . Human C4A and alpha 2-macroglobulin preferentially form amide linkages while human C3 primarily forms ester linkages with hydroxyl groups . We have examined the thioester in C3 and found evidence of strong preferences for certain carbohydrates, indications of selectivity for specific positions on those carbohydrates and a preference for terminal sugars in polysaccharides . A testable set of rules are derived from these findings which predict preferred attachment sites on polysaccharides . A computer model of the effect of different reactivities on activation of the alternative pathway of complement suggested that organisms might greatly alter their susceptibility to complement with small changes in carbohydrate structure . While a random selection of 20 biological particles showed no correlation between activation and C3b attachment efficiency, subsets of related organisms differing primarily in their surface polysaccharide exhibited stronger correlations . The strongest correlation occurred in a series of the yeasts (Cryptococcus neoformans) possessing capsular polysaccharides with one, two, three or four branching xylose sugars per repeating unit . These organisms exhibited capture efficiencies for metastable C3b from 12% (one-xylose strain) to 41% (four-xylose strain).

Chest, 1994 Sep, 106(3), 697 - 702
Transthoracic needle aspiration in the study of pulmonary infections in patients with HIV; Falguera M et al.; STUDY OBJECTIVE: To evaluate the safety and efficacy of transthoracic aspiration with an ultrathin needle in the microbiologic diagnosis of pulmonary infections in HIV-infected patients . DESIGN: Retrospective review of cases . SETTING: A 500-bed teaching hospital in Lleida, Spain . PATIENTS: Forty-five HIV-infected patients admitted between March 1989 and March 1993 with clinical and roentgenographic evidence of pulmonary infection and without contraindications for transthoracic needle aspiration (TNA) . INTERVENTIONS: Forty-seven TNAs were performed in the emergency room (20) or during hospitalization (27) . The TNA procedures were done without premedication and without fluoroscopic guidance . Specimens were processed using routine microbiologic and cytologic techniques; in addition, polymerase chain reaction (PCR) for Pneumocystis carinii was carried out since March 1992 . Development of adverse effects was carefully evaluated . RESULTS: The TNA was effective in 29 (62 percent) out of 47 procedures . The diagnosis was obtained for 14 of 15 patients with P carinii pneumonia, 8 out of 14 patients with bacterial pneumonia, and 4 out of 12 patients with tuberculosis . Other pathogens recovered were Nocardia asteroides, Cryptococcus neoformans, Rhodococcus equi, and Mycobacterium avium . No false-positive results were obtained . Pneumothorax developed in eight (17 percent) procedures, but only one procedure resulted in a pleural drainage; the incidence of other adverse effects was low and clinically irrelevant . CONCLUSION: Our study suggests that TNA can be a useful technique in establishing the etiologic diagnosis of pulmonary infections in HIV-infected patients, with a good sensitivity, high specificity, and relatively low incidence of serious complications, with TNA appearing as a reliable alternative to more uncomfortable methods.

Arch Biochem Biophys, 1994 Sep, 313(2), 304 - 9
Purification and characterization of glucose-6-phosphate dehydrogenase from Cryptococcus neoformans: identification as "nothing dehydrogenase"; Niehaus WG et al.; Glucose-6-phosphate dehydrogenase (EC 1.1.1.49) was purified from Cryptococcus neoformans, a basidiomyceteous yeast that is an opportunistic pathogen of AIDS patients . The enzyme had a subunit molecular weight of 5 x 10(4), a specific activity of 50 units mg-1, and Km values for NADP and glucose-6-phosphate of 1.6 and 24 microM, respectively . The enzyme catalyzed the dehydrogenation of glucose, in the presence of dimethylsulfoxide, with Km of 5 mM and Vmax 10% of that with glucose-6-phosphate . pH profiles indicated the presence of a group with pKa of 6.6 that is involved in catalysis, and groups with pKas of about 8.8 that are involved in binding of NADP and glucose-6-phosphate . The enzyme was inhibited by NADPH, competitive versus NADP, with Ki of 1 microM, and by zinc ion, competitive versus glucose-6-phosphate, with Ki of 2 microM . Crude enzyme extract catalyzed an appreciable rate of reduction of NADP in the absence of added substrate, a "nothing dehydrogenase" activity . This activity was shown to be due to the presence of glucose-6-phosphate in the crude extract . It was calculated that cells of C . neoformans contain about 25 mumol of glucose-6-phosphate per gram, wet weight.

J Am Acad Dermatol, 1994 Sep, 31(3 Pt 2), S64 - 7
Management of systemic manifestations of fungal disease in patients with AIDS; Stevens DA; In patients with AIDS with cryptococcosis, prompt diagnosis is essential . Poor results with conventional therapy (amphotericin-5FC) have led to exploration of the azoles . Both fluconazole and itraconazole have given good short-term results with less toxicity . However, cure is achieved far less often than in other compromised hosts . Fluconazole is also useful to prevent relapse after successful initial amphotericin therapy, particularly from genitourinary foci . In both histoplasmosis and aspergillosis, itraconazole has produced impressive therapeutic results, and in histoplasmosis, secondary prophylaxis as well . In coccidioidomycosis results thus far have not been better than conventional amphotericin therapy, especially in initial treatment.

J Am Acad Dermatol, 1994 Sep, 31(3 Pt 2), S56 - 9
Common superficial fungal infections in immunosuppressed patients; Odom RB; HIV-positive patients and those persons immunosuppressed as a result of other diseases or chemotherapy are especially susceptible to mycotic infections . The superficial fungal infections seen most often in patients with HIV infection include seborrheic dermatitis, various dermatophyte infections, candidiasis, and onychomycosis . Uncommonly, systemic fungal infections, such as candidiasis, histoplasmosis, cryptococcosis, and coccidioidomycosis, may disseminate to the skin, producing a wide variety of cutaneous lesions . All cutaneous lesions in these patients should be biopsied and cultured if any question exists regarding the diagnosis . The diagnosis of superficial and deep mycotic infections in HIV-positive patients can be particularly difficult because the clinical presentation varies greatly and is often atypical.

Am J Med Sci, 1994 Sep, 308(3), 192 - 5
Case report: cutaneous manifestations of cryptococcosis; Haight DO et al.; Cutaneous cryptococcosis usually is associated with concurrent systemic infection and actually may develop before clinical manifestations of cryptococcal meningitis become apparent . It is rare for a cryptococcal infection to be localized only to the skin . A case of cutaneous cryptococcosis is described in an immunocompromised patient who initially had a rash and a positive serum cryptococcal antigen titer, but no central nervous system involvement . The papular pustular skin lesions disappeared after 8 weeks of therapy with amphotericin B, which was stopped secondary to progressive azotemia . Less than 2 months after therapy, the skin lesions recurred, again without evidence of systemic disease . Treatment with oral fluconazole resulted in a gradual resolution of the cutaneous lesions . The pathogenesis of cryptococcosis is discussed, with emphasis on the management of cutaneous cryptococcosis.

Infect Immun, 1994 Sep, 62(9), 4085 - 6
Relationship between superoxide dismutase and melanin in a pathogenic fungus; Jacobson ES et al.; Since melanin is considered a virulence factor in Cryptococcus neoformans, its suppression at 37 degrees C has been perplexing . We now show an opposite thermal regulation of superoxide dismutase (SOD), consistent with a compensatory mechanism . Moreover, we demonstrate normal SOD and catalase levels in albino, oxygen-sensitive mutants . These results suggest that melanin is an antioxidant factor comparable in importance to SOD.

Infect Immun, 1994 Sep, 62(9), 3864 - 72
Molecular and idiotypic analysis of antibodies to Cryptococcus neoformans glucuronoxylomannan; Casadevall A et al.; Antibodies to the Cryptococcus neoformans capsular glucuronoxylomannan (GXM) form the basis of two potential therapeutic intervention strategies, i.e., conjugate vaccines and passive antibody therapy . To better understand the molecular basis of the antibody response, the heavy- and light-chain immunoglobulin variable region (VH and VL, respectively) sequences of seven monoclonal antibodies (MAbs) to GXM were determined . Rabbit anti-idiotypic serum was made to the previously characterized murine MAb 2H1 and used to study MAb 2H1 idiotype expression in other GXM-binding MAbs and immune sera . MAb E1 originated from a C3H/HeJ mouse immunized with C . neoformans serotype A polysaccharide . MAbs 471, 1255, 339, 3C2, 386, and 302 originated from BALB/c mice immunized with polysaccharide of serotypes A, A, B, C, D, and D, respectively, conjugated to sheep erythrocytes . In the E1, VH uses V11 from the T15 gene family and JH3 and has a D segment of three amino acids, and the VL uses a VKSer-like gene family element and JK5 . In MAbs 471 and 3C2, the VH uses VH7183-like gene family elements and JH2 and has D segments of seven amino acids, and the VL uses VK5.1 and JK1 . In MAbs 1255 and 339, the VH uses VH10-like gene elements and JH4 and has six codon D segments, and the VL uses a VK21-like gene element and JK5 . In MAbs 302 and 386, respectively, the VH uses VHGAM-like gene elements and JH2 and JH3 and has six and four codon D segments, and VL uses VK4/5-like gene elements and JK1.VH usage, MAb 2H1 idiotype expression, and fine specificity mapping define a minimum of three GXM epitopes which elicit protective antibodies . The results confirm that the antibody response is highly restricted, suggest a close relationship between molecular structure and serological properties, and provide insight into protein structural motifs important for GXM binding.

Jpn J Antibiot, 1994 Sep, 47(9), 1145 - 59
{A clinical study on fluconazole against pulmonary mycosis associated with respiratory diseases}; Takamoto M et al.; In 34 hospitals in Kyushu area, the clinical effects and safety of fluconazole (FLCZ) against pulmonary mycosis were studied . To a total of 108 patients with respiratory diseases was FLCZ administered . The results were as follows . 1 . Sixty-six cases were evaluable for the clinical efficacy of FLCZ . In 8 cases of pulmonary cryptococcosis, the clinical efficacy rate was 100% (8/8) . In 58 cases of pulmonary aspergillosis, it was 43.1% (25/38) . Overall, the clinical efficacy rate was 50% (33/66) . 2 . Fungi were eliminated in 3 of 6 cases in which Cryptococcus was detected, and were eliminated in 8 and reduced in 4 of 30 cases in which Aspergillus spp . including A . fumigatus were detected . 3 . Side effects were observed in 5 of 87 cases (5.7%), none of them was serious, however . Abnormal results of laboratory tests that might be related to the FLCZ administration were observed in 5 cases (5.7%) . 4 . From these results, fluconazole appears to be a potent antifungal agent for treatment of pulmonary mycosis.

Rev Clin Esp, 1994 Sep, 194(9), 689 - 91
{Cryptococcosis with exclusive cutaneous presentation in a patient with AIDS}; Tapiz A et al.; We report an exclusively cutaneous case of cryptococcosis, which is exceptional . He was a 33 years old patient with the acquired immunodeficiency syndrome who presented with an ulcer-necrotic lesion at the nasal wings with a long and torpid evolution . Finally, culture and biopsy were diagnostic of cryptococcosis . We ruled out affection of other organs and the cryptococcal antigen was negative in serum and cerebrospinal fluid . The patient was treated with fluconazole and had a good clinical course . Its emphasized the scarcity of this form of presentation as well as the lack of specificity of its lesions and the necessity of ruling out other locations once the fungus is isolated in the skin . Diagnosis is simple through skin biopsy and culture . Its important to determine the cryptococcal antigen . We comment on the current approaches to treatment during acute and maintenance phases, after the appearance of the new imidazolic compounds such as fluconazole.

J Am Acad Dermatol, 1994 Sep, 31(3 Pt 2), S47 - 50
The AIDS epidemic; Conant MA; The nature of the clinical presentation of HIV infection continues to evolve over time . New cutaneous (e.g., seborrheic dermatitis, onychomycosis, and tinea pedis) and systemic (e.g., Aspergillus fumigatus and Penicillium marneffei) opportunistic fungal infections can now be added to the classic clinical markers for progressive HIV infection, such as Kaposi's sarcoma, Pneumocystis carinii pneumonia, Mycobacterium avium intercellulare infections, and cryptococcal meningitis . The fact that the appearance of many of these fungal diseases is directly correlated with the patient's CD4 cell count is a valuable tool for ongoing clinical evaluation . Although systemic manifestations characterize a progression from asymptomatic HIV infection to AIDS, many of the signs of disease progression are cutaneous . Prophylaxis against many of the potentially life-threatening systemic opportunistic infections associated with HIV positivity has had a positive impact on the life expectancy of patients with AIDS.

AIDS Res Hum Retroviruses, 1994 Sep, 10(9), 1079 - 87
Enhancement of HIV type 1 infectivity in vitro by capsular polysaccharide of Cryptococcus neoformans and Haemophilus influenzae; Pettoello-Mantovani M et al.; High concentrations of the cryptococcal capsular polysaccharide (CCP) are present in the serum, cerebrospinal fluid or both in the majority of AIDS patients infected with Cryptococcus neoformans . Because the prognosis of AIDS patients infected with cryptococcus is poor, we investigated whether the presence of CCP enhanced HIV-1 infection . The presence of CCP markedly increased the infectivity of HIV-1-infected H9 cells and subsequent production of infectious HIV-1 and formation of syncytia . In addition to enhancing the infectivity of H9 cells infected with laboratory isolates of HIV-1, the presence of CCP also increased the infectivity of peripheral blood mononuclear cells (PBMCs) infected with primary field strains of HIV-1 . The in vitro infectivity of PBMCs from 20 of 44 HIV-1-infected individuals was significantly increased when cultured with CCP . Furthermore, HIV-1 was isolated from the PBMCs of three of these individuals only when cultured in the presence of CCP . CCP increased the binding of HIV-1 and recombinant gp120 to H9 cells and recombinant CD4, respectively . Thus, it is possible that the enhancement of HIV-1 infectivity by CCP is due to its capacity to increase the adherence of HIV-1 to target cells . Whereas the capsular polysaccharide of Haemophilus influenzae also markedly enhanced the infectivity of HIV-1, the capsular polysaccharides of C . freundii or S . flexneri had minimal effects on the infectivity of HIV-1 . This indicated that the capacity to enhance HIV-1 infectivity was a property of polysaccharides from some pathogens and not others.(ABSTRACT TRUNCATED AT 250 WORDS)

J Clin Microbiol, 1994 Sep, 32(9), 2309 - 11
Evaluation of new monoclonal antibody-based latex agglutination test for detection of cryptococcal polysaccharide antigen in serum and cerebrospinal fluid; Kiska DL et al.; We evaluated the performance of CRYPTO-LEX (Trinity Laboratories, Inc., Raleigh, N . C.), a new mouse immunoglobulin M monoclonal antibody latex agglutination reagent which reacts with the capsular polysaccharide of the four serogroups of Cryptococcus neoformans . This test was compared with CALAS (Meridian Diagnostics, Cincinnati, Ohio) for the ability to detect cryptococcal antigen in serum and cerebrospinal fluid (CSF) . A total of 580 clinical specimens (327 serum and 253 CSF samples), primarily from human immunodeficiency virus-infected patients, were tested in this study . Sixty-seven specimens (44 serum and 23 CSF samples) were positive for cryptococcal antigen with both tests, and 511 (282 serum and 229 CSF samples) were negative . The two latex reagents agreed for 326 of 327 serum specimens (44 positives and 282 negatives) . One serum specimen with a titer of 1:2 was CALAS positive but CRYPTO-LEX negative . The titer correlation coefficient for the two tests was 0.884 when two highly discordant serum specimens were eliminated from analysis of the data . The two latex tests agreed for 252 of 253 CSF specimens (23 positives and 229 negatives) . One specimen with a titer of 1:2 was positive with CALAS and negative by CRYPTO-LEX . The correlation coefficient of the two tests for CSF titers was 0.886 . The sensitivity and specificity of CRYPTO-LEX were 97 and 100%, respectively, with a 99.6% correlation with CALAS . These data show that the performance of CRYPTO-LEX is comparable to that of CALAS for detection of cryptococcal antigen in serum and CSF.

J Clin Microbiol, 1994 Sep, 32(9), 2307 - 8
Effect of potential interference factors on performance of enzyme immunoassay and latex agglutination assay for cryptococcal antigen; Engler HD et al.; The PREMIER Cryptococcal Antigen Enzyme Immunoassay (Meridian Diagnostics) did not give discrepant results with rheumatoid factor, syneresis fluid, or serum macroglobulins from systemic lupus erythematosis patients . The Cryptococcal Antigen Latex Agglutination System (Meridian Diagnostics) did cross-react with syneresis fluid but not with the other serum factors tested.

J Clin Microbiol, 1994 Sep, 32(9), 2158 - 61
Elimination of false-positive serum reactivity in latex agglutination test for cryptococcal antigen in human immunodeficiency virus-infected population; Whittier S et al.; We recently tested serum from a human immunodeficiency virus-infected patient for the presence of cryptococcal antigen using the Meridian latex agglutination (LA) test (Cryptococcal Antigen Latex Agglutination System) . Two pronase-treated serum specimens from the patient had LA titers of 80 and 160, but the patient had no evidence of cryptococcal disease . The serum was negative for rheumatoid factor, a well-documented cause of false-positive LA reactions . Seven blood culture supernatants from the patient were also LA positive, but were culture negative for cryptococcus . When the sera and blood culture supernatants were treated with 0.01 M 2-beta-mercaptoethanol (2-ME), the agglutinating activity was ablated . Similar results were seen when the sera were tested by two other commercial LA assays . Serum and cerebrospinal fluid specimens from patients with confirmed cryptococcal disease were treated with 2-ME, and the results were compared with those obtained after pronase (sera) or heat (cerebrospinal fluid) inactivation . The titers were identical (n = 56) or within 1 dilution (n = 3) . One hundred serum specimens from human immunodeficiency virus-seropositive patients with no known history of cryptococcal disease were examined to determine the frequency of false-positive reactivity in this patient population . Of this group, three were positive following pronase treatment . One remained positive after 2-ME treatment; the remaining two were negative . These data indicate that 2-ME can be used to eliminate nonspecific reactivity in the LA test without affecting true-positive results.

Antimicrob Agents Chemother, 1994 Sep, 38(9), 2162 - 4
Effect of in vivo macrophage colony-stimulating factor on fungistasis of bronchoalveolar and peritoneal macrophages against Cryptococcus neoformans; Nassar F et al.; Macrophage colony-stimulating factor (M-CSF) given subcutaneously at a dose of 2.5 mg/kg of body weight (4.75 x 10(6) U/kg) to CD-1 male mice 8 to 12 weeks old was found to enhance significantly the fungistasis of bronchoalveolar macrophages (BAM) against Cryptococcus neoformans . When M-CSF was given 1, 3, 7, 9, or 13 days before an ex vivo challenge with C . neoformans, fungistasis was increased (P ranged from < 0.05 to < 0.001) compared with that induced by control BAM . A maximum effect was seen by days 1 and 3 after administration of M-CSF . Twenty-one days after M-CSF, BAM did not produce significantly enhanced fungistasis . M-CSF also significantly enhances the fungistatic effect of peritoneal macrophages (PM) if given 1, 3, and 7 days prior to testing against C . neoformans in comparison with control PM (P ranged from < 0.05 to < 0.001) . PM did not produce enhanced fungistasis 9 or 13 days after administration of M-CSF . These studies demonstrating in vivo enhancement of anticryptococcal activity of macrophages with M-CSF provide a rationale for in vivo use of M-CSF to enhance resistance to infection with C . neoformans.

Antimicrob Agents Chemother, 1994 Sep, 38(9), 2158 - 61
Effect of macrophage colony-stimulating factor on anticryptococcal activity of bronchoalveolar macrophages: synergy with fluconazole for killing; Brummer E et al.; The anticryptococcal activity of murine bronchoalveolar macrophages (BAM) and their synergy with fluconazole (FCZ) was studied . BAM cultured with tissue culture medium for 48 to 72 h were fungicidal (24 to 39%) in a 3-h killing assay . However, net killing of Cryptococcus neoformans did not continue when culture time was extended to 24 h, although BAM were fungistatic (88 to 98%) . Treatment with macrophage colony-stimulating factor (M-CSF; 5,000 U/ml, 48 h) did not significantly increase BAM killing of a low challenge dose in 3-h assays compared with control BAM . However, M-CSF-treated BAM were significantly more fungistatic against higher challenge doses in the 3-h assays . FCZ was not fungicidal at 5 micrograms/ml but was highly fungistatic (98 and 99% at 24 and 48 h, respectively) . M-CSF-treated BAM acted synergistically with FCZ (2.5 micrograms/ml) for significantly greater killing than control BAM, 55% versus 20% and 96% versus 45% at 24 h and 48 h, respectively . Killing by M-CSF BAM and FCZ (5.0 micrograms/ml) was significantly (P < 0.01) greater than that by control BAM and FCZ at 48 h . These findings indicate an important collaborative role for BAM and FCZ in killing C . neoformans, and this is enhanced by M-CSF.

Antimicrob Agents Chemother, 1994 Sep, 38(9), 2029 - 33
Sterol composition of Cryptococcus neoformans in the presence and absence of fluconazole; Ghannoum MA et al.; Analysis of the sterol compositions of 13 clinical isolates of the pathogenic yeast Cryptococcus neoformans obtained from five patients with recurring cryptococcal meningitis showed that, unlike Candida albicans, the major sterols synthesized by this yeast were obtusifoliol (range, 21.1 to 68.2%) and ergosterol (range, 0.0 to 46.5%) . There was considerable variation in the sterol contents among the 13 isolates, with total sterol contents ranging from 0.31 to 5.9% of dry weight . The isolates from the five patients who had relapses had different total sterol contents and compositions in comparison with those of the pretreatment isolates, indicating either that the sterols had been changed by therapy or that the patients were infected with new isolates with different sterol compositions . Growth of the cryptococcal isolates in the presence of subinhibitory concentrations of fluconazole (0.25x the MIC) significantly altered the sterol content and pattern . The total sterol content decreased in nine isolates and increased in four isolates in response to pretreatment with fluconazole . Fluconazole had no consistent effect on ergosterol levels . In contrast, fluconazole caused a decrease in obtusifoliol levels and an increase in 4,14-dimethylzymosterol levels in all isolates . These results indicate extensive diversity in sterol content, sterol composition, and sterol synthesis in response to subinhibitory concentrations of fluconazole in C . neoformans strains . We propose that fluconazole inhibits the sterol synthesis of C . neoformans by interfering with both 14 alpha-demethylase-dependent and -independent pathways . No correlation between the sterol compositions of C . neoformans isolates and their susceptibilities to fluconazole was found.

Mycopathologia, 1994 Sep, 127(3), 131 - 4
The Eiken Latex test for detection of a cryptococcal antigen in cryptococcosis . Comparison with a monoclonal antibody-based latex agglutination test, Pastorex Cryptococcus; Tanaka K et al.; A latex agglutination test for cryptococcal antigen, the Eiken Latex test (Eiken, Tokyo, Japan), was compared with a monoclonal antibody-based agglutination assay, Pastorex Cryptococcus (Diagnostics Pasteur, Marneur-la-Coquette, France) . In a murine model of disseminated cryptococcosis, the kinetics of the antigen titers by the Eiken Latex were similar to those by the Pastorex Cryptococcus, but sensitivity was much higher . In HIV-negative patients with pulmonary cryptococcosis, a cryptococcal antigen was detected in 6 of 10 patients by the Eiken Latex test and in only 3 of those patients by the Pastorex Cryptococcus . The results indicate that the Eiken Latex is more sensitive for the detection of the cryptococcal antigen, even in non-disseminated cryptococcosis . The sensitivity and specificity of the Eiken Latex were examined using 195 sera from 25 patients with pulmonary cryptococcosis and 170 patients with non-cryptococcosis . The cutoff value of > or = 1:8 showed a sensitivity of 76% (19/25) and a specificity of 98.9% (168/170).

AIDS, 1994 Sep, 8(9), 1271 - 6
Pulmonary cryptococcosis associated with HIV-1 infection in Rwanda: a retrospective study of 37 cases; Batungwanayo J et al.; OBJECTIVES: To study the demographic, clinical, radiographic and diagnostic features, the clinical course and therapeutic response of pulmonary cryptococcosis in HIV-1-infected patients . DESIGN: Retrospective review . SETTING: The Department of Medicine of an urban reference hospital in Central Africa . METHODS: All the records of HIV-1-infected patients with pulmonary cryptococcosis were reviewed retrospectively with regard to the parameters described above . RESULTS: Over a 3-year period, pulmonary cryptococcosis was diagnosed in 37 HIV-1-infected Rwandan patients (21 men, 16 women; mean age, 35 years; range, 26-55 years) . Twenty-nine patients (78%) had primary pulmonary cryptococcosis . Cough (94%), weight loss (65%), fever (51%), dyspnoea (46%), thoracic pain (30%), headache (13%) and haemoptysis (8%) were the predominant clinical findings . A diffuse interstitial infiltrate on chest radiograph was observed in 76% of the patients, an alveolar pattern in 19%, mediastinal and/or hilar adenopathy in 11%, nodules and pleural effusion each in 5% . Bronchoalveolar lavage, with a yield of 82%, was found to be the most sensitive diagnostic procedure . Screening of cryptococcal antigen in the serum failed to detect cases of primary pulmonary cryptococcosis . Twelve patients with primary pulmonary cryptococcosis treated with itraconazole as acute and maintenance therapy were all protected against disseminated cryptococcal disease; seven out of 10 (70%) of those who did not receive a specific anticryptococcal drug developed disseminated cryptococcal disease . CONCLUSION: Pulmonary cryptococcosis is not a rare complication of HIV-1 infection in Rwanda . Its clinical and radiographic patterns are non-specific and bronchoalveolar lavage is the procedure of choice for its diagnosis . The natural history of untreated primary pulmonary cryptococcosis is disseminated cryptococcal disease . Itraconazole is highly effective in the prevention of disseminated cryptococcal disease in patients with primary pulmonary cryptococcosis.

Mycoses, 1994 Sep-Oct, 37(9-10), 325 - 7
Isolation of Cryptococcus neoformans from pigeon (Columba livia) droppings in Mexico City; Castanon-Olivares LR et al.; To determine the ecological and epidemiological significance of pigeon excrement in cryptococcosis in Mexico City, 251 samples of pigeon droppings were studied . These were collected from houses, public buildings, churches, parks and pigeon nests . Each sample was suspended 1:10 in isotonic saline solution and then cultured in Staib medium . Identification of Cryptococcus neoformans was performed based on the development of brown-coloured colonies and the presence of encapsulated yeasts . Of 251 samples, 52 (20.7%) were positive for Cr . neoformans . The highest frequency was observed in droppings from public buildings (31.2%), followed by churches (22.0%) and houses (13.3%) . No significant differences in isolation frequency were observed between fresh or dried excrement . All isolates obtained were Cr . neoformans var . neoformans . As in other studies on Cr . neoformans from pigeons, performed in other countries, these frequency data are considered 'normal' . The results, however, accentuate the potential risk of cryptococcosis acquisition, especially now that cryptococcosis frequency is increasing in Mexico, mainly in AIDS patients.

P N G Med J, 1994 Sep, 37(3), 161 - 5
Cryptococcal meningitis in children in Papua New Guinea: a reminder; Brown N et al.; Two young males from Central Province were referred to Port Moresby General Hospital with chronic headaches . In each case the initial impression of tuberculous meningitis needed revision in the light of strongly positive cryptococcal serology . Cryptococcal meningitis occurs with sufficient frequency in Papua New Guinea that it should be considered in cases of raised intracranial pressure, ataxia, cranial neuropathy and visual disturbances . Delay in treatment may be disastrous . In contrast to the developed world where fungal meningitides show a predilection for the immunosuppressed, the experience to date in Papua New Guinea is that the majority of cases in both adults and children occur in ostensibly immunocompetent individuals . The epidemiology, clinical course and current treatment of this potentially curable disease are discussed.

J Acquir Immune Defic Syndr, 1994 Sep, 7(9), 924 - 30
Safety profile of didanosine among patients with advanced HIV disease who are intolerant to or deteriorate despite zidovudine therapy: results of the Canadian Open ddI Treatment Program; Montaner JS et al.; The aim of this study was to ascertain the safety profile of didanosine (Videx; ddI) within the Canadian Open Treatment Program . Symptomatic HIV+ subjects with AIDS or ARC or CD4 < 200/mm3 were eligible to receive didanosine if they were either (a) intolerant to zidovudine (Retrovir, ZDV) or (b) deteriorating despite ZDV therapy . The dose of didanosine (powder formulation) was based on body weight as follows: > or = 75 kg, 375 mg b.i.d.; 50-74 kg, 250 mg b.i.d.; 35-49 kg, 167 mg b.i.d . Participants were monitored with physical examinations and prespecified laboratory studies by their treating physicians on a monthly basis . Follow-up data were collected in a central database through five regional coordinators . A total of 168 physicians across Canada participated in the program, and 825 subjects who started didanosine after July 1, 1990, were included in the analysis . Of these, 97% were male, 88% homosexual, and 59% had a prior diagnosis of AIDS . Reasons for enrolling was ZDV intolerance in 39%, failure in 25%, both in 32%, and other in 4% . Data were prospectively collected until July 31, 1991 . Total follow-up was 3,440 patient-months and median follow-up was 4.3 months . A total of 78 deaths were reported, 44 of which occurred within a month after the last dose of didanosine . Causes of death included AIDS-related unspecified causes (13 patients), MAC (11), wasting (7), AIDS-related CNS involvement other than OI's (7), Kaposi's sarcoma (7), Pneumocystis carinii pneumonia (6), sudden death, including suicides and accidents (6), lymphoma (5), toxoplasmosis (4), cryptococcosis (4), cytomegalovirus (3), unspecified causes (2), tuberculosis (1), PML (1), and disseminated histoplasmosis (1) . Didanosine was discontinued in 140 (17%) subjects during the study period due to adverse events.(ABSTRACT TRUNCATED AT 250 WORDS)

Ann Thorac Surg, 1994 Aug, 58(2), 333 - 8
Thoracotomy for pulmonary mycoses in non-HIV-immunosuppressed patients; Temeck BK et al.; Pulmonary mycoses can be life threatening in patients who are in an immunocompromised state stemming from defective host defenses or the use of certain treatment regimens . In 36 immunosuppressed patients undergoing thoracotomy for the treatment of pulmonary fungal disease, the underlying cause of immunosuppression was malignancy (n = 9), Wegener's granulomatosis (n = 4), hematologic disorders (aplastic anemia, 5-Q minus syndrome, or myelofibrosis) (n = 6), or chronic granulomatous disease of childhood (n = 17) . The mean age of the patients was 25 years, and 89% were symptomatic (fever, n = 27; cough, n = 20; chest pain, n = 14; and other, n = 13) . Chest x-ray studies revealed the presence of cavitary disease (n = 7), a mass (n = 8), infiltrates (n = 20), or cavity and infiltrate (n = 1) . A preoperative diagnosis was lacking in 23 of the 36 patients . Procedures included wedge biopsy (n = 13), segmentectomy with or without wedge or chest wall resection (n = 5), lobectomy with or without chest wall resection (n = 16), wedge resection plus completion pneumonectomy (n = 1), and segmentectomy plus completion pneumonectomy (n = 1) . Fungi identified included Aspergillus (n = 23), Zygomycetes (n = 4), Cryptococcus (n = 3), and other (n = 6; 1 each), and specific antifungal treatment was instituted in 34 of the patients (94%) . The 31% operative (ie, < 30-day or inhospital) mortality was chiefly due to multiorgan system failure (9/11).(ABSTRACT TRUNCATED AT 250 WORDS)

Am J Respir Cell Mol Biol, 1994 Aug, 11(2), 130 - 7
Role of human alveolar macrophages as antigen-presenting cells in Cryptococcus neoformans infection; Vecchiarelli A et al.; The contribution of human alveolar macrophages (AM) from normal subjects in Cryptococcus neoformans infection was investigated . AM were able to efficiently phagocytize the fungus after opsonization, but killing activity did not occur at an effector-to-target ratio of 10:1 in a 6-h incubation since there was an inhibition of phagosome-lysosome fusion . Moreover, the role of AM as antigen-presenting cells was investigated . Cryptococcus-laden AM were co-cultured with autologous T lymphocytes and lymphoproliferation was determined; a massive blastogenic response of alpha/beta TCR-bearing T lymphocytes was observed . The response started after 1 day of co-culture and was triggered and regulated by IL-1 produced by AM in response to C . neoformans . Finally, the antigen-presentation process was associated with HLA class II DR molecules . This finding suggests that AM play a key role in the lung as antigen-presenting cells and, through the secretion of IL-1, regulate proliferation and activation of T lymphocytes, which are important in mediating pulmonary clearance . We speculate that in immunodepressive conditions, the impairment of AM functions could contribute to the spread of C . neoformans infection from the lung.

Infect Immun, 1994 Aug, 62(8), 3189 - 96
Anticryptococcal resistance in the mouse brain: beneficial effects of local administration of heat-inactivated yeast cells; Blasi E et al.; Using a murine model, we have previously shown that brain resistance to local infection with opportunistic fungi is affected by manipulation of the host myelomonocytic compartment . Here, we demonstrate that intracerebral administration of heat-inactivated Cryptococcus neoformans (H-CN) yeast cells results in a consistent enhancement of mouse survival to subsequent local challenge with lethal doses of C . neoformans . The phenomenon, more pronounced upon double H-CN treatment, is associated with (i) massive local inflammatory response, (ii) reduced growth of the fungus within the brain, and (iii) induction of delayed-type hypersensitivity . Moreover, H-CN treatment confers protection against local heterologous challenges . Our data provide initial evidence that intracerebral administration of H-CN results in the establishment of aspecific and specific immune responses; the mechanisms of elicitation and relative contributions to host antimicrobial resistance remains to be elucidated.

Cell Immunol, 1994 Aug, 157(1), 1 - 10
Anticryptococcal activity of macrophages: role of mouse strain, C5, contact, phagocytosis, and L-arginine; Brummer E et al.; The antifungal activity of nonactivated resident murine peritoneal macrophages for Cryptococcus neoformans was studied . Macrophages from five of six mouse strains tested had significant (40 to 80%) fungistatic activity, depending on the inoculum size, in a 24-hr coculture system . Macrophages from two outbred (SW and ICR) and three inbred (BALB/c, C57Bl/6, and DBA/2J) strains were fungistatic . Only macrophages from outbred CD-1 mice lacked fungistatic activity . Heat-inactivated and C5-deficient sera did not support phagocytosis or fungistasis by resident BALB/c or DBA/2 macrophages . Fungistasis correlated with contact, complement, and phagocytosis . Macrophages were studied in a Lab-Tek chamber slide system where noningested cells were washed away . Fungistasis in this system was similar to that found with a microtest plate coculture method where a smaller inoculum was cultured continuously with macrophages . After ingestion of yeast cells, CD-1 macrophages could be activated for fungistasis (70%) with interferon-gamma plus lipopolysaccharide . Activated BALB/c macrophages had increased fungistasis but were not fungicidal . NG-Monomethyl-L-arginine (200 microM), which inhibited the fungistatic activity of activated CD-1 macrophages, did not inhibit inherent fungistatic activity of BALB/c macrophages . The fungistatic mechanism of BALB/c macrophages resembled that reported for resident human macrophages.

Mod Pathol, 1994 Aug, 7(6), 647 - 51
Geographical pathology profile of AIDS in Puerto Rico: the first decade; Climent C et al.; Postmortem histopathological changes in 100 adult patients with AIDS who died in Puerto Rico from 1982 to 1991 were studied and tabulated . Modes of HIV transmission were reviewed . Patient ages ranged from 21 to 60 yr . Gender composition for the patient group was 83 men (average age, 35 yr) and 17 women (average age, 39 yr) . Sixty-eight of the patients were injecting-drug users, 20 were homosexual and bisexual men, seven were women who had had heterosexual contact with men at risk for HIV, and one was a man who had had heterosexual contact with prostitutes . Only one case was linked to transfusions of blood . Twenty-seven men and seven women were serologically tested for antibodies and all were HIV seroreactive . The most common causes of infection and the frequency of each were as follows: Pneumocystis carinii in 49 patients; cytomegalovirus in 43; Toxoplasma gondii in 30; Candida species in 24; Histoplasma capsulatum in 18; Mycobacterium species in 14; Cryptococcus species in eight; and Strongyloides stercoralis in six patients . Infection by Schistosoma mansoni (10 patients) was considered incidental because this trematode is endemic in Puerto Rico . The lung was the organ most frequently infected by a single microorganism: Pneumocystis carinii affected 49 patients . However, Cryptococcus species was the microorganism that infected more body systems: 20 different organs in eight patients . Nineteen patients had microglial nodular encephalitis, 86 patients had lymphocyte depletion in the spleen, and 58 had lymphocyte depletion in lymph node tissue . Twenty-seven men had testicular maturation arrest and variable germ cell loss . Three patients had malignant lymphoma, and two had Kaposi's sarcoma.(ABSTRACT TRUNCATED AT 250 WORDS)

J Clin Microbiol, 1994 Aug, 32(8), 1992 - 6
Evaluation of a novel colorimetric broth microdilution method for antifungal susceptibility testing of yeast isolates; Pfaller MA et al.; A comparative evaluation of two broth microdilution methods for antifungal susceptibility testing of 600 clinical yeast isolates (Candida spp., Torulopsis glabrata, and Cryptococcus neoformans) against amphotericin B, fluconazole, and flucytosine (5FC) was conducted . Microdilution testing was performed according to National Committee for Clinical Laboratory Standards (NCCLS) recommendations (NCCLS document M27-P) . By using the growth control for comparison, reference microdilution MIC endpoints for amphotericin B were scored as the lowest concentration at which a score of 0 (complete absence of growth) was observed, and those for 5FC and fluconazole were scored at the lowest concentration at which a score of 2 (prominent decrease in turbidity) (MIC-2) was observed . The second microdilution method employed a colorimetric endpoint using an oxidation-reduction indicator (Alamar Biosciences, Inc., Sacramento, Calif.) and was assessed independently of the reference microdilution MICs . The MICs for the two microdilution test systems were read after 24 and 48 h of incubation . Excellent agreement between the reference and colorimetric microdilution MICs was observed . Overall agreement was > or = 95% for all three drugs at 24 h . At 48 h, agreement was > or = 98% for amphotericin B and 5FC but dropped to 84% for fluconazole . Given these results it appears that the colorimetric microdilution approach to antifungal susceptibility testing may be viable alternative to the NCCLS reference method for testing yeasts.

Clin Neurol Neurosurg, 1994 Aug, 96(3), 250 - 3
Latex agglutination test negative cryptococcal meningitis in an immuno-competent individual: a case report; Agrawal JP et al.; We report a case with progressive mental deterioration and persistent low grade fever, who was diagnosed to have cryptococcal meningitis . This case is unique in that the cryptococcal latex agglutination antigen test was consecutively negative . The diagnosis was made by sequential CSF culture.

Clin Transplant, 1994 Aug, 8(4), 365 - 8
Cutaneous cryptococcosis mimicking bacterial cellulitis in a liver transplant recipient: case report and review in solid organ transplant recipients; Singh N et al.; Cutaneous cryptococcosis is an uncommon manifestation of disseminated cryptococcal disease . We report a liver transplant recipient presenting with onset over 3 days of progressive pain and swelling of the lower extremity and foot with erythema and heat . Cryptococcal cellulitis was documented, but in retrospect the clinical presentation was indistinguishable in presentation and appearance from acute bacterial cellulitis . The patient also proved to have concomitant cryptococcal septic arthritis; the presence of cryptococcal antigen in the synovial fluid allowed a rapid and definitive diagnosis . Subsequently, cultures of skin, synovial fluid, and blood were all positive for cryptococci . Cryptococcus should be considered in the differential diagnosis of bacterial cellulitis in a liver transplant recipient not responding to antibacterial therapy.

Clin Infect Dis, 1994 Aug, 19 Suppl 1, S33 - 40
Clinical aspects of fungal infection in organ transplant recipients; Hibberd PL et al.; Fungal infections following solid organ transplantation remain a major cause of morbidity and mortality . Candida species and Aspergillus fumigatus continue to account for the majority of these infections, although the attack rate is higher among recipients of organs other than kidneys because those patients receive more immunosuppressive therapy . Although amphotericin B remains the drug of choice for treatment of invasive aspergillosis, its toxicity profile limits its widespread use . Recent experience suggests that fluconazole may be a safe and effective alternative for the treatment of fungal infections caused by Candida species or Cryptococcus neoformans . Prevention of fungal infections remains one of the most important goals in the field of transplantation . New approaches--such as the use of "preemptive therapy," or prophylaxis, for patients at greatest risk of developing infection--may assist in attainment of this goal.

J Med Assoc Thai, 1994 Aug, 77(8), 440 - 3
Clinical study of HIV disease in the lower area of northern Thailand in 1994; Swasdisevi A; Seventy-seven HIV-positive patients admitted to Budhachinaraj Hospital between February and July 1994 were studied . The sex ratio between male and female was 4.1:1 The majority of cases were sexually transmitted . There were 25 cases of symptomatic HIV and 52 cases of full-blown AIDS . The treatment in this study was both medical and psychological . Cryptococcal infection is common in the lower area of northern provinces . Zidovudine has not been widely used . The AIDS patients died of P . carinii pneumonia, cryptococcal meningitis, tuberculous meningitis and toxoplasmic encephalitis respectivelyPIP: A psychiatrist/drug abuse specialist reviewed the medical records of 77 HIV-positive patients aged 15-61 at Budhachinaraj Hospital in Phitsanulok, Northern Thailand, during February-July 1994 to determine the HIV disease situation in Phitsanulok and the nearby provinces . (The first HIV-positive IV drug user in Phitsanulok was identified in June 1988.) The sex ratio between male and female was 4.1:1 (i.e., 62 males and 15 females) . 55 of the 77 patients were 20-39 years old . All but one HIV-positive patients were Thai . Leading occupations were farmer/gardener (27) and worker (27) . 62 had completed primary school . Most of the HIV-positive patients were from Phitsanulok (46), followed by those from Sukothai (10) . 52 patients had full-blown AIDS, the leading opportunistic infections being cryptococcal meningitis (23), Pneumocystis carinii pneumonia (13), and pulmonary tuberculosis (10) . Seven of nine cases of advanced HIV disease had CD4 cell counts under 50 cells/cubic mm and two had under 150 cells/cu . mm . 15 HIV cases died of opportunistic infections .

Nihon Kyobu Shikkan Gakkai Zasshi, 1994 Aug, 32(8), 819 - 23
{A case of primary pulmonary cryptococcosis showing infiltrative shadows in the unilateral lung field}; Shibuya Y et al.; A case of primary pulmonary cryptococcosis is reported . A 76-year-old man, without underlying disease or immunological abnormalities, was admitted to the hospital . Chest X-ray revealed diffuse infiltrative shadows considered at first to be community-acquired pneumonia . A diagnosis of pulmonary cryptococcosis was performed using fluconazole, miconazole and transbronchial inhalation of amphotericin B . Cryptococcal antigen detection was performed by two latex agglutination methods: Crypto-test and Sero-direct test (Eiken-test) . Comparing the results of the two tests, sensitivity was superior with the Sero-direct test, but the correlation between the titers of the two tests was good.

Nihon Kyobu Shikkan Gakkai Zasshi, 1994 Aug, 32(8), 778 - 84
{A case of HTLV-1 carrier associated with pulmonary cryptococcosis and thymoma}; Inoue Y et al.; A 46-year-old female was admitted to our hospital on December 1991 for further examination of an abnormal shadow on chest X-ray . A huge mass in the upper mediastinum and a thin-walled cavitary lesion in the right upper lobe were found by chest radiography and computed tomography . On March 2, 1992, surgical resection was performed with pathological diagnosis of thymoma for the mediastinal mass and pulmonary cryptococcosis for the cavitary lesion . Although ATL cells were not found in the peripheral blood, anti-HTLV-1 antibody was found to be positive . Natural killer cell activity was lower than normal control and other tests of humoral and cell-mediated immunity were normal . Histological examination of the specimens obtained from the thymoma revealed lymphocytic predominance without atypical cells such as ATL cells, but with integration of HTLV-1 proviral DNA . There seemed to be a causal relationship between HTLV-1 carrier state and thymoma . Since there are no reported cases of HTLV-1 carrier associated with pulmonary cryptococcosis and thymoma, we report the first case with a review of the literature.

Gene, 1994 Jul 22, 145(1), 135 - 8
Cloning, sequence analysis and expression of the gene encoding imidazole glycerol phosphate dehydratase in Cryptococcus neoformans; Parker AR et al.; A cDNA from Cryptococcus neoformans, encoding imidazole glycerol phosphate dehydratase (IGPD), was isolated by complementation of a his3 mutant strain of Saccharomyces cerevisiae . The C . neoformans HIS3 cDNA encodes an approx . 22-kDa protein with a high degree of amino-acid sequence similarity to IGPDs from ten other microorganisms, as well as Arabidopsis thaliana . Most striking are two conserved HHXXE regions and several conserved His, Asp and Glu residues . The cDNA was engineered for expression in Escherichia coli and an approx . 26-kDa protein was identified by SDS-PAGE . DNA and N-terminal sequence analyses confirmed that this protein was C . neoformans IGPD . Furthermore, IGPD assays of crude extracts from IGPD-producing E . coli cells demonstrated that the C . neoformans protein was catalytically active.

Lancet, 1994 Jul 9, 344(8915), 110 - 3
Disseminated Penicillium marneffei infection in southeast Asia; Supparatpinyo K et al.; Disseminated infection with the fungal pathogen Penicillium marneffei is, after extrapulmonary tuberculosis and cryptococcal meningitis, the third most common opportunistic infection in HIV disease in northern Thailand . We report the clinical, microbiological, and therapeutic features of a large series of HIV-infected adults with disseminated P marneffei infection . From August, 1987, to June, 1992, 92 patients with P marneffei infection confirmed by culture were seen at Chiang Mai University Hospital, of whom 86 were also infected with HIV . Clinical information was available for 80 of these patients . The most common presenting symptoms and signs were fever (92%), anaemia (77%), weight loss (76%), and skin lesions (71%) . 87% of patients presenting with skin lesions had generalised papules with central umbilication . Presumptive diagnosis was made in 50 patients by microscopic examination of Wright's-stained bone-marrow aspirate and/or touch smears of skin biopsy or lymph-node biopsy specimens . Most patients who were diagnosed responded initially to amphotericin or itraconazole, whereas most who were not diagnosed and treated died . 12 patients relapsed within 6 months of cessation of treatment . P marneffei has become an important pathogen of HIV-associated opportunistic infection in ThailandPIP: Penicillium marneffei (PM) is the only Penicillium species which is dimorphic and can cause systemic mycosis in human beings; it is endemic in southeast Asia and China . The prevalence of PM infection has increased substantially during the past few years, occurring exclusively among patients infected with HIV . After extrapulmonary tuberculosis and cryptococcal meningitis, disseminated infection with PM is the most common opportunistic infection of HIV disease in northern Thailand . The clinical, microbiological, and therapeutic features of a large series of well-documented cases have not, however, been reported . The authors describe the clinical and laboratory features of 80 HIV-infected adults with disseminated PM infection seen over the period August 1987 - June 1992 at Chiang Mai University Hospital, Thailand . Subjects were of mean age 32.4 years in a range of 18-63 . 74 subjects were male and 76 acquired HIV via heterosexual relations . Fever was present in 92%, anemia in 77%, weight loss in 76%, and skin lesions in 71%, while 87% of patients presenting with skin lesions had generalized papules with central umbilication . Most patients who were diagnosed responded initially to amphotericin or itraconazole, while most who were not diagnosed and treated died . More precisely, 40 of the 68 patients treated responded to the therapy . Twelve patients relapsed within six months of cessation of treatment .

Dtsch Med Wochenschr, 1994 Jul 8, 119(27), 956 - 8
{Idiopathic CD4 lymphocytopenia with lethal Salmonella typhimurium sepsis}; Burg S et al.; In April 1991, a then 43-year-old woman fell ill with a systemic cryptococcal infection which responded well to antimycotic treatment . Four months later she was found to have a T-helper cell deficiency (48/microliters, 15%) . Since August 1992 she noted an increased tendency towards infections and had recurrent fever bouts over 4 weeks, which led to her hospitalization in January 1993 . Repeated HIV tests were negative . During the first 4 days she was free of infection, but developed a temperature of 39.1 degrees C on the fifth day, and within a few hours a fulminant septicaemia with cardiorespiratory failure developed ending fatally the same day . Blood cultures drawn during fever bouts grew Salmonella typhimurium by the time of her death . Lymphocyte differentiation revealed absolute and relative reduction in the number of CD4-lymphocytes (158/microliters; 18%), retrospectively providing the diagnosis of idiopathic CD4-lymphocytopenia.--In cases such as this there is the need of including opportunistic and masked disease entities in the differential diagnosis, even in the absence of HIV infections, and start early treatment.

Am J Otol, 1994 Jul, 15(4), 515 - 22
The ear in the acquired immunodeficiency syndrome: I . Temporal bone histopathologic study; Michaels L et al.; A postmortem histopathologic investigation of temporal bones of patients with the acquired immunodeficiency syndrome (AIDS) was performed after microslicing, acid decalcification of the slices and paraffin embedding . Histopathologic changes in 49 temporal bones from 25 patients included severe otitis media in five patients (20%), low-grade otitis media in fifteen (60%), labyrinthine cryptococcosis in two, Kaposi's sarcoma deposit in the eighth nerve of one, and cytomegalovirus (CMV) inclusion-bearing cells in the inner and middle ear of six (24%) . It was possible to identify the CMV genome by in situ hybridization in only two bones and expression of CMV antigen by immunohistochemistry in none, probably because of prolonged decalcification in acid . The ear is no less susceptible to AIDS-associated diseases than any other organ, and is particularly prone to CMV infection.

Curr Opin Rheumatol, 1994 Jul, 6(4), 408 - 14
Mycobacterial and fungal infections of bone and joints; Meier JL; The incidence of tuberculosis of the bone or joint is increasing . The number of Mycobacterium tuberculosis isolates that are resistant to multiple antibiotics is also on the rise . In response to the changing epidemiology, the approach to treatment of tuberculosis has been considerably modified . Laboratory methodology is improving to facilitate diagnosis and management of this disease . A variety of nontuberculous mycobacteria may also cause disease of skeletal structures . Mycobacterium haemophilum is an emerging pathogen in immunosuppressed patients with a proclivity for infecting bones and joints . The availability of the triazoles has substantially altered the therapeutic approach to fungal infections of bone or joint . Itraconazole can now be considered as therapy of blastomycosis, coccidioidosis, histoplasmosis, or sporotrichosis . Fluconazole is useful in cryptococcal infection, but its role in candida osteoarticular infection remains to be defined.

Am J Trop Med Hyg, 1994 Jul, 51(1), 56 - 9
Opportunistic invasion of the heart in Hispanic patients with acquired immunodeficiency syndrome; Altieri PI et al.; One hundred consecutive patients who died of the acquired immunodeficiency syndrome (AIDS) were studied with an emphasis on the heart . Thirty-two patients showed pathologic changes . The pathologic findings included infection by Histoplasma capsulatum, Toxoplasma gondii, Mycobacterium tuberculosis, cytomegalovirus . Cryptococcus neoformans, and atypical mycobacteria . Noninfectious pathologic findings included nonspecific myocarditis, focal necrosis, focal fibrosis, and acute subendocardial infarction.

Lab Invest, 1994 Jul, 71(1), 113 - 26
Experimental murine pulmonary cryptococcosis . Differences in pulmonary inflammation and lymphocyte recruitment induced by two encapsulated strains of Cryptococcus neoformans; Curtis JL et al.; BACKGROUND: Cryptococcus neoformans, the most common cause of lethal mycosis in AIDS, usually causes only subclinical pneumonitis in normal hosts . However, cryptococcosis can induce various pulmonary inflammatory reactions, and pulmonary cellular immunity is postulated to prevent dissemination . We hypothesized that cryptococcal strains possess different capacities to induce recruitment to the lungs of inflammatory cells, especially lymphocytes, which are necessary for cryptococcal clearance . EXPERIMENTAL DESIGN: We examined the pulmonary response of CBA/J mice to intratracheal inoculation with C . neoformans of either of two strains: 52D (ATCC 24067), which rarely kills immunocompetent mice; and 145A (ATCC 62070), which is uniformly fatal . From 2-42 days after inoculation, lungs were either examined grossly and microscopically or were enzymatically digested and inflammatory cells counted and analyzed by flow cytometry . At 42 days, organism burden in lung and brain was quantified by colony-forming unit assay . RESULTS: Pulmonary inflammation differed greatly between the two strains . Strain 52D induced dense perivascular and alveolar inflammation; infection progressed to day 21 and then waned . In contrast, strain 145A induced delayed, meager lymphocytic infiltration and slight alveolitis; organisms grew progressively . Recovery of inflammatory cells increased by day 13 with strain 52D, but not until day 31 with strain 145A . Although all lymphocyte subsets were greater in 52D infection, the disparity was greatest for CD4+ T cells . Nevertheless, lymphocytes from paratracheal nodes of infected mice proliferated in vitro to heat-killed cryptococci, indicating immune recognition of both strains . At day 42, strain 52D lightly infected lungs but not brain, whereas strain 145A heavily infected lungs and brain . CONCLUSIONS; Cryptococcal strains differ in their capacity to induce pulmonary cellular inflammation, especially CD4+ T cell recruitment . Our results suggest that strain-specific difference in the organism's ability to induce (or evade) pulmonary inflammation contributes to the outcome of infection.

Neurology, 1994 Jul, 44(7), 1198 - 202
Bilateral seventh nerve palsy: analysis of 43 cases and review of the literature; Keane JR; Among inpatients with facial diplegia, one-half (22 patients) had benign, self-limited causes, including Bell's palsy (10), Guillain-Barre syndrome (5), multiple idiopathic cranial neuropathies (3), brainstem encephalitis (2), Miller Fisher syndrome (1), and association with benign intracranial hypertension (1) . Nine patients had tumors: four meningeal, three prepontine, and two intrapontine . Syphilis (2 patients), Hansen's disease (1), cryptococcal meningitis with acquired immunodeficiency syndrome (1), and tuberculous meningitis (1) constituted those with an infectious etiology, while miscellaneous causes included one patient each with diabetes, sarcoidosis, head trauma, pontine tegmental hemorrhage, undiagnosed Mobius syndrome in an adult, systemic lupus erythematosus with severe neuropathy, and slowly progressive degeneration--possibly bulbospinal neuronopathy . Bilaterality makes facial neuropathy a more ominous sign with widely varying causes that requires prompt investigation.

Arch Pathol Lab Med, 1994 Jul, 118(7), 757 - 9
Placental cryptococcosis in a mother with systemic lupus erythematosus; Molnar-Nadasdy G et al.; There are many pregnant mothers who have acquired immunodeficiency syndrome or who require immunosuppressive therapy for sundry reasons . Despite this, we have been able to find only one English-language report of placental cryptococcosis . We have had an opportunity to treat a pregnant mother who suffered from cryptococcal meningitis that complicated steroid treatment for lupus erythematosus . At 31 weeks' gestation, fetal distress necessitated delivery by cesarean section . The placenta had focally abundant intervillous and perivillous cryptococcal yeast cells, but there was no chorioamnionitis or villitis . Although there were no clinical or placental signs of transplacental infection, immunohistochemical labeling of villous stromal cells showed a conspicuously increased number of fetal macrophages.

South Med J, 1994 Jul, 87(7), 751 - 2
HIV-negative "AIDS" in Kentucky: a case of idiopathic CD4+ lymphopenia and cryptococcal meningitis; Ramirez JA et al.; Here we describe a case of unexplained CD4+ T-lymphocyte depletion and cryptococcal meningitis in a patient without evidence of human immunodeficiency virus (HIV) infection . This newly recognized syndrome has been named idiopathic CD4+ lymphopenia (ICL) . When HIV infection is suspected in a patient with an opportunistic infection, a CD4+ lymphocyte count should be obtained, even if the patient's HIV test is negative . Patients with persistently low CD4 counts (< 300 cells/microL, or < 20%) who show no evidence of HIV infection, who have no defined immunodeficiency, and who are not receiving therapy associated with CD4 depletion have disease that meets the definition of ICL, and the case should be reported to the Centers for Disease Control.

J Infect Dis, 1994 Jul, 170(1), 60 - 7
Human immunodeficiency virus (HIV)-infected human blood monocytes and peritoneal macrophages have reduced anticryptococcal activity whereas HIV-infected alveolar macrophages retain normal activity; Cameron ML et al.; Human immunodeficiency virus type 1 (HIV-1) infection causes immune dysfunction . Mononuclear phagocytes (MNP) are immune effector cells against some intracellular pathogens and reservoirs for HIV-1 . This study determined effects of HIV-1 on MNP-mediated antifungal function . MNP from seronegative volunteers were inoculated with HIVBal or HIVIIIB . MNP were infected with an avirulent clone of Cryptococcus neoformans; 48 h later, MNP were lysed and yeasts were counted . Viral replication was determined by reverse transcriptase and by visualization of cytopathic effects . Monocytes and peritoneal macrophages exhibited reduced anticryptococcal activity 14 days after infection with HIVBal but retained normal activity when infected with HIVIIIB . Loss of anticryptococcal activity correlated with viral replication . Alveolar macrophages retained normal anticryptococcal activity whether infected with HIVBal or HIVIIIB . In vitro MNP-mediated antifungal activity may be altered by HIV-1 infection; this altered activity appears to depend on viral tropism, viral replication, and MNP tissue origin.

J Infect Dis, 1994 Jul, 170(1), 238 - 42
High-dose fluconazole for treatment of cryptococcal disease in patients with human immunodeficiency virus infection . The California Collaborative Treatment Group; Haubrich RH et al.; Eight patients (6, cryptococcal meningitis; 2, high-titer cryptococcal antigenemia) were treated with 800 mg/day fluconazole to assess the safety and efficacy of high-dose fluconazole as primary therapy . Five patients with meningitis had resolution of clinical symptoms and all 6 had negative cerebrospinal fluid (CSF) cultures by day 82 (median, 21 days) . One meningitis patient developed neurologic deterioration and was switched to amphotericin B at day 18, but CSF culture was negative on day 15 of fluconazole therapy . In 2 patients with cryptococcal antigenemia, clinical symptoms resolved and serum antigen titers declined rapidly; they did not progress to meningitis . Therapy was well tolerated, with mainly gastrointestinal side effects . Four patients had mild increases in liver enzymes; another had a threefold increase in alkaline phosphatase . Mean steady-state serum level of fluconazole was 45 +/- 15 micrograms/mL, and paired CSF and serum levels were 40 +/- 14 and 49 +/- 14 micrograms/mL, respectively . High-dose fluconazole appears safe and effective for cryptococcal disease in AIDS patients.

J Infect Dis, 1994 Jul, 170(1), 173 - 9
Macrophage colony-stimulating factor induction of enhanced macrophage anticryptococcal activity: synergy with fluconazole for killing; Brummer E et al.; Enhancement of anticryptococcal activity in macrophages by macrophage colony-stimulating factor (M-CSF) and possible synergy between macrophages and fluconazole for killing of Cryptococcus neoformans were tested . M-CSF (48 h)-treated macrophages underwent dramatic morphologic changes and inhibited cryptococcal multiplication by 96% +/- 4%, which was greater (P < .001) than that of macrophages cultured in medium alone . M-CSF (5000 units/mL) induced optimal anticryptococcal activity but did not increase percentage of phagocytosis . NG-mono-methyl-L-arginine did not affect enhanced fungistatic activity . For a very fluconazole-sensitive isolate, fungistatic macrophages synergized with fungistatic doses of fluconazole for killing; for a less sensitive isolate, synergy was significant only when macrophages were activated with M-CSF or interferon-gamma plus lipopolysaccharide; for a fluconazole-resistant isolate, macrophages collaborated with fluconazole for additive fungistasis but not killing, and M-CSF-treated macrophages were significantly more fungistatic with fluconazole than were nonactivated macrophages.

Mol Cell Biol, 1994 Jul, 14(7), 4912 - 9
Complementation of a capsule-deficient mutation of Cryptococcus neoformans restores its virulence; Chang YC et al.; Capsule formation plays a significant role in the pathogenicity of Cryptococcus neoformans . To study the molecular basis of capsule synthesis, the capsule-deficient phenotype of a mutant strain was complemented by transformation . A plasmid rescued from the resulting Cap+ transformant complemented a cap59 mutation which was mapped previously by classical recombination analysis . Gene deletion by homologous integration resulted in an acapsular phenotype, indicating that we have identified the CAP59 gene . The CAP59 gene was assigned to chromosome I by Southern blot analysis of contour-clamped homogeneous electric field gel electrophoresis-resolved chromosomes of C . neoformans var . neoformans . Sequence comparison of genomic and cDNA clones indicated the presence of six introns . CAP59 encoded a 1.9-kb transcript and a deduced protein of 458 amino acids . Analysis of the nucleotide sequence revealed little similarity to existing sequences in the data bank . When the capsule-deficient phenotype was complemented, the originally avirulent C . neoformans strain became virulent for mice . In addition, the acapsular strain created by gene deletion of CAP59 lost its virulence . This work demonstrates the molecular basis for capsule-related virulence and that the CAP59 gene is required for capsule formation.

J Exp Med, 1994 Jul 1, 180(1), 365 - 9
Human astrocytes inhibit Cryptococcus neoformans growth by a nitric oxide-mediated mechanism; Lee SC et al.; Cryptococcus neoformans is an opportunistic fungus that causes life-threatening meningoencephalitis in 5-10% of patients with acquired immune deficiency syndrome . Cryptococcal meningoencephalitis is characterized by a lymphohistiocytic infiltrate, accumulation of encapsulated forms of C . neoformans, and varying degrees of glial reaction . Little is known about the contribution of endogenous central nervous system cells to the pathogenesis of cryptococcal infections . In this study, we investigated the role of astrocytes as potential effector cells against C . neoformans . Primary cultures of human fetal astrocytes, activated with interleukin 1 beta plus interferon gamma inhibited the growth of C . neoformans . The inhibition of C . neoformans growth was paralleled by production of nitrite, and reversed by the inhibitors of nitric oxide (NO.) synthase, NG-methyl-mono-arginine and NG-nitro-arginine methyl ester . The results suggest a novel function for human astrocytes in host defence and provide a precedent for the use of NO . as an antimicrobial effector molecule by human cells.

Infect Immun, 1994 Jul, 62(7), 3004 - 7
Susceptibility of melanized and nonmelanized Cryptococcus neoformans to nitrogen- and oxygen-derived oxidants; Wang Y et al.; Melanized Cryptococcus neoformans cells were less susceptible than nonmelanized cells to the fungicidal effects of nitrogen- and oxygen-derived oxidants . The results support the hypothesis that the phenoloxidase enzyme system contributes to virulence by protecting C . neoformans against nitrogen- and oxygen-derived oxidative antimicrobial molecules produced by immune effector cells.

Infect Immun, 1994 Jul, 62(7), 2857 - 64
Occurrences, immunoglobulin classes, and biological activities of antibodies in normal human serum that are reactive with Cryptococcus neoformans glucuronoxylomannan; Houpt DC et al.; Serum obtained from normal human subjects contains antibodies reactive in an enzyme-linked immunosorbent assay with the glucuronoxylomannan (GXM) of Cryptococcus neoformans . The frequency of occurrence of class-specific antibodies among normal subjects was 28% for immunoglobulin G (IgG), 98% for IgM, and 3% for IgA . Anti-GXM antibodies with kappa light chains occurred in 98% of normal subjects, while the occurrence of lambda light chains was 28% . Each of five subjects with high levels of anti-GXM IgG antibodies had readily detectable antibodies of the IgG2 isotype; two of the five subjects had readily detectable IgG1 antibody . An examination of sera from human immunodeficiency virus-infected patients showed that human immunodeficiency virus infection was accompanied by a significant decrease in the occurrence of IgM antibodies and anti-GXM antibodies with kappa light chains; these decreases occurred early in infection when CD4 counts were still > or = 500 cells per microliter . A slight but not statistically significant decrease in the occurrence of anti-GXM IgG antibodies was seen only in patients with CD4 levels of < 200 cells per microliter . Sera from normal subjects with high levels of anti-GXM IgG antibodies were examined to identify any contribution of the antibodies to complement activation or to opsonization of the yeast cells . An analysis of the kinetics for activation and binding of C3 to the yeast cell showed no pattern of quantitative or qualitative differences between sera with high or low levels of anti-GXM IgG antibodies . Phagocytosis studies showed that the naturally occurring IgG antibodies did not contribute to opsonization of the yeast cells.

Infect Immun, 1994 Jul, 62(7), 2849 - 56
Cloning of a Cryptococcus neoformans gene, GPA1, encoding a G-protein alpha-subunit homolog; Tolkacheva T et al.; We have isolated a gene, GPA1, from Cryptococcus neoformans by the PCR technique . DNA sequencing of the GPA1 clone suggested that it encodes a protein homologous to the G-protein alpha-subunit family . Comparison of the deduced amino acid sequence of the GPA1-encoded protein revealed that it is about 45% identical to several mammalian Gi alpha subunits and 48% identical to the G alpha protein Gpa2 from Saccharomyces cerevisiae . G alpha proteins are known to be involved in mating of other yeasts, such as S . cerevisiae and Schizosaccharomyces pombe . Southern analysis demonstrated that GPA1 is present in a single copy within the Cryptococcus genome . Isolation of the cDNA for GPA1 confirmed that the gene contains six introns within the coding region . The GPA1 transcript was identified by Northern (RNA) analysis as a 1.6-kb RNA present in exponentially growing cells of both the alpha and a mating types . Moreover, the abundance of this transcript increased in cells shifted to starvation medium . Coincubation of alpha and a cells on starvation medium is required for mating of cryptococcal cells . Thus, our results are consistent with the involvement of C . neoformans GPA1 in mating.

Antimicrob Agents Chemother, 1994 Jul, 38(7), 1507 - 14
Mouse-human immunoglobulin G1 chimeric antibodies with activities against Cryptococcus neoformans; Zebedee SL et al.; Passive antibody administration is a potentially useful approach for the therapy of human Cryptococcus neoformans infections . To evaluate the efficacy of the human immunoglobulin G1 (IgG1) constant region against C . neoformans and to construct murine antibody derivatives with reduced immunogenicities and longer half-lives in humans, two mouse-human IgG1 chimeric antibodies were generated from the protective murine monoclonal antibodies 2D10 (IgM) and 18B7 (IgG1) . The 2D10 mouse-human IgG1 chimeric antibody (ch2D10) had significantly lower binding affinity than its parent murine antibody (m2D10), presumably because of a loss of avidity contribution on switching from IgM to IgG . The 18B7 mouse-human IgG1 chimeric antibody (ch18B7) had higher affinity for cryptococcal polysaccharide antigen than its parent murine antibody (m18B7) . ch18B7 and ch2D10 promoted phagocytosis of C . neoformans by primary human microglial cells and the murine J774.16 macrophage-like cell line . ch18B7 and m18B7 enhanced fungistatic or fungicidal activity of J774.16 cells and prolonged the survival of lethally infected mice . We conclude that the human IgG1 constant chain can be effective in mediating antifungal activity against C . neoformans . ch18B7 or similar antibodies are potential candidates for passive antibody therapy of human cryptococcosis.

J Emerg Med, 1994 Jul-Aug, 12(4), 491 - 7
The acquired immune deficiency syndrome: an overview for the emergency physician, Part 2; Guss DA; Human immunodeficiency virus (HIV) affects all organ systems . Infection of the heart can manifest with evidence of myocarditis, pericarditis, or cardiomyopathy . The most common gastrointestinal symptom is diarrhea, which can result from infection with a variety of bacterial, fungal, or protozoal organisms . In about 15% of cases, no pathogen is recognized and the diarrhea syndrome is termed AIDS enteropathy . Any portion of the alimentary tract can be affected as well as the liver, gallbladder, and pancreas . Cryptosporidium, a previously infrequent cause of human illness, has emerged as an important pathogen in the HIV-infected patient and is responsible for chronic diarrhea, cholecystitis, and biliary tract obstruction . Evidence of neurologic involvement is present in more than 80% of patients at the time of autopsy . Cryptococcal meningitis, toxoplasma encephalitis, and neurosyphilis are the most often encountered central nervous system infections . While all three are responsive to therapy, treatment must be prolonged or persist for the duration of the patient's life to avoid recurrence . Peripheral nervous system manifestations include myelopathy, myopathy, and a variety of peripheral neuropathies . Retinal infection with cytomegalovirus (CMV) and toxoplasma can lead to irreversible loss of vision . Cotton wool spots are a common benign physical finding that must be differentiated from the early signs of CMV or toxoplasma infection . Management of the HIV-infected patient, while most often conducted by specialists in Internal Medicine or Infectious Diseases, is often an issue for the emergency physician . Many of the commonly afforded therapies are reviewed . Part 1 of this two-part series discussed the pathophysiology and clinical expression, epidemiology, laboratory testing, and the general clinical manifestations of AIDS, as well as dermatologic, pulmonary, and cardiac symptoms . Part 2 discusses the gastrointestinal, neurologic, and ocular symptoms, as well as the treatment and management of the AIDS patient.

J Antimicrob Chemother, 1994 Jul, 34(1), 83 - 92
The postantibiotic effect of antifungal agents against common pathogenic yeasts; Turnidge JD et al.; A total of ten strains of Candida spp . and Cryptococcus neoformans were examined for the presence of the postantibiotic effect (PAE) after 0.5-2 h exposure to amphotericin B, 5-fluorocytosine, miconazole and ketoconazole . Significant PAEs were observed for amphotericin B and 5-fluorocytosine, but none for the imidazoles . The duration of the PAEs of amphotericin B ranged from 0.5-10.4 h for the Candida spp . and 2.8-10.6 h for the cryptococcos, while 5-fluorocytosine induced PAEs from 0.8-7.4 h and 2.4-5.4 h, respectively . Even though no PAEs were demonstrated for the imidazoles, the growth rate was persistently reduced by continuous exposure to concentrations as low as 1/1000 of the MIC of these agents . These findings may have implications for dosing antifungal agents in systemic yeast infections.

Curr Genet, 1994 Jul, 26(1), 54 - 61
Formation of a minichromosome in Cryptococcus neoformans as a result of electroporative transformation; Varma A et al.; A minichromosome of approximately 270 kilobases was generated following complementation of a ura5 mutant strain of C . neoformans with the plasmid pURA5g2 . This is the first report of the in-vivo generation of a minichromosome by the method of electroporative transformation . The minichromosome occurred at a relatively high (> 20%) frequency in transformants that were stable for uracil protoprophy . The minichromosome was maintained in linear form as a large extrachromosomal element of the normal karyotype . Gel-purified DNA from the minichromosome readily transformed the ura5 mutant of C . neoformans . Southern-blot analysis of the minichromosome revealed the presence of multiple copies of the URA5 gene and ribosomal DNA sequences in addition to containing telomere-like sequence repeats . The minichromosome was transmitted through mitosis and meiosis with extremely-high fidelity.

Acta Paediatr, 1994 Jul, 83(7), 780 - 2
Hyper-IgM immunodeficiency with disseminated cryptococcosis; Iseki M et al.; We describe two siblings with X-linked hyper-IgM immunodeficiency . One patient developed disseminated cryptococcosis . Co-culture of this patient's T cells with normal B cells suppressed IgG and IgA production . The CD40 ligand gene of one patient was examined and contained a nonsense mutation at nucleotide 475 . CD40 ligand is a membrane protein which is expressed on activated T cells and induces B-cell proliferation . These results suggest that there is a defect in T- and B-cell interactions in this immunodeficiency syndrome . It is also possible that patients with this syndrome are predisposed to cryptococcal infections.

Clin Infect Dis, 1994 Jul, 19(1), 60 - 6
Chronic candidal meningitis: an uncommon manifestation of candidiasis; Voice RA et al.; Chronic meningitis is an uncommon manifestation of candidiasis . We present the case of an elderly woman who had symptoms such as headache, malaise, and fever for 8 months and was found to have Candida albicans meningitis, and we review 17 similar cases . An underlying illness or risk factor for candidiasis was present in only 13 (72%) of the 18 patients . Headache, fever, and nuchal rigidity were the predominant clinical findings . Analysis of CSF showed either mononuclear or neutrophilic pleocytosis, an elevated protein level, and a decreased level of glucose . Only 17% of CSF smears were positive, and only 44% of initial CSF cultures yielded Candida species . In four cases, Candida species grew only after special techniques were used; in three cases, CSF cultures remained negative . The overall mortality associated with candidal meningitis was 53%, but among 12 patients who were treated and followed, the rate was 33% . In addition to acute meningitis seen with disseminated infection, Candida species can cause chronic meningitis that mimics tuberculosis and the more common fungal meningitides, such as cryptococcosis.

Mycopathologia, 1994 Jul, 127(1), 15 - 7
Cryptococcal meningitis with malaria . A case report; Ashiru JO et al.; Cryptococcal meningitis is an uncommon infection globally, including Nigeria . This systemic fungal infection often is associated with immunodeficiency . The most common causes of meningitis in Nigeria in the 2-3 year age group are the malaria parasites and bacteria . The concomitant infections of Cryptococcal neoformans and Plasmodium falciparum are uncommon . We present here the report of a case of fatal cryptococcal meningitis with malaria infection in a 2 year old child from Nigeria (one of the malaria endemic regions of the world) . This case emphasizes the importance of doing a combination of fungal and bacterial cultures as well as looking for malarial parasites in the determination of etiological agents of meningitis in any hospital in Africa . We suggest that cerebrospinal fluid from meningitis cases must be cultured using Sabouraud dextrose agar and any growth on the agar must be examined using Indian ink.

J Clin Microbiol, 1994 Jul, 32(7), 1680 - 4
Comparison of commercial kits for detection of cryptococcal antigen; Tanner DC et al.; Although kits to detect cryptococcal antigen are used widely to diagnose cryptococcal infection, the comparative performance of commercially available assays has not been evaluated in the past decade . Therefore, we compared the sensitives and specificities of five commercially available kits for detecting cryptococcal antigen (four latex agglutination test kits--Calas {Meridian Diagnostics})--Crypto-LA {International Biological Labs}, Myco-Immune {MicroScan}, and Immy {Immunomycologics}--and an enzyme immunoassay kit, Premier {Meridian Diagnostics}) with culture for the diagnosis of cryptococcal meningitis and fungemia . Of 182 cerebrospinal fluid (CSF) and 90 serum samples submitted for cryptococcal antigen and fungal culture, 49 (19 and 30 samples, respectively) from 20 patients had a culture positive for Cryptococcus neoformans . For CSF specimens, the sensitivities and specificities of all kits were comparable (sensitivity, 93 to 100%; specificity, 93 to 98%) . There was a significant difference in sensitivities of the kits when serum samples were tested with the International Biological Labs and MicroScan kits, which do not pretreat serum with pronase . These kits were less sensitive (sensitivity, 83%) than the Immy and Meridian latex kits (sensitivity, 97%), which do pretreat with pronase . The sensitivity of the Meridian enzyme immunoassay kit was comparable to that of the pronase-containing latex kits . These kits were of equivalent specificities (93 to 100%) when testing serum . Some of the currently available kits have limitations that need to be recognized for proper interpretation of results . Specifically, the use of pronase on serum samples reduces the number of false-positive results, and a titer of < or = 1:4 can be a false-positive result when CSF samples are being tested.

Aktuelle Radiol, 1994 Jul, 4(4), 188 - 91
{CT-morphologic aspects of the liver in patients with HIV infection}; Schedel H et al.; CT examinations of the liver in HIV-infected patients show more frequent pathological findings . The extended spectrum of differential diagnosis and atypical manifestations of disorders in immunodeficient patients needs to be considered in the interpretation of CT scans . Difficulties in the differential diagnosis of focal hepatic lesions in HIV-infected patients are demonstrated in the following . Besides the relatively common findings in HIV-infection such as hepato-or hepatosplenomegalia, lymphoma, and inflammatory changes of the bowel an infection with Cryptococcus neoformans, hepatitis, and local steatosis of the liver are discussed as the rare causes for suspect computertomographic findings in the live of HIV-infected patients . The examinations were obtained consecutively in 76 HIV-infected patients during abdominal CT staging.

Infect Immun, 1994 Jul, 62(7), 2930 - 9
Regulation of cytokine production during the expression phase of the anticryptococcal delayed-type hypersensitivity response; Buchanan KL et al.; Effects of both positive and negative regulatory T cells on cellular infiltration and cytokine production during the expression phase of the anticryptococcal immune response were examined . Tamp cells, which are induced by cryptococcal antigen, significantly amplify the anticryptococcal delayed-type hypersensitivity response, whereas a cascade of T suppressor (Ts) cells inhibits the response and decreases the clearance of Cryptococcus neoformans during an infection . By using the gelatin sponge implantation model, we found that Tamp cells do not stimulate a significant increase in cellular infiltration into the sponges in response to cryptococcal antigen compared with that into delayed-type hypersensitivity-reactive sponges in immune control mice . However, Tamp cells do stimulate significant increases in the production of gamma interferon and interleukin-2 (IL-2) in the antigen-injected sponges over the level of the representative cytokine in antigen-injected sponges from the immune control mice . Likewise, Ts1 cells, induced with cryptococcal antigen, do not significantly affect antigen-induced cellular infiltration into sponges in immune mice . In contrast, decreased levels of gamma interferon and IL-2 are observed in antigen-injected sponges from Ts1-cell-recipient, immunized mice compared with those of the positive immune controls . The presence of either Tamp or Ts1 cells in immunized mice stimulates increased production of IL-5 but not IL-4 over that of the positive immune controls.

Phytochemistry, 1994 Jul, 36(4), 1047 - 51
Prenylated isoflavanone from the roots of Erythrina sigmoidea; Nkengfack AE et al.; A novel prenylated isoflavanone, sigmoidin I, has been isolated from the roots of Erythrina sigmoidea, in addition to the known isoflavones, corylin and neobavaisoflavone and the known pterocarpan, phaseollidin . Its structure was established as 7,4'-dihydroxy-3'-methoxy-5'-(3-methylbut-2-enyl) isoflavanone by means of spectroscopic analyses and chemical transformations . Neobavaisoflavone displayed antifungal potency in vitro with minimum inhibitory concentrations against Aspergillus fumigatus and Cryptococcus neoformans, of 50 mg ml-1.

Mycoses, 1994 Jul-Aug, 37(7-8), 275 - 9
Disseminated cryptococcosis in a patient with AIDS; Reblin T et al.; We report the case of a 31-year-old AIDS patient who had generalized cryptococcal disease with involvement of the lungs, bone marrow, gastrointestinal tract and skin as well as chorioretinitis which may have been due also to Cryptococcus neoformans infection . Initially there was no involvement of the central nervous system . The patient recovered after 43 days' treatment with fluconazole and amphotericin B and flucytosine initially . Four months later he presented with a cryptococcal splenic abscess despite secondary prevention with fluconazole and twice-weekly liposomal amphotericin B . After splenectomy the patient was discharged in good health . One year later he died of cryptococcal meningitis.

Mycoses, 1994 Jul-Aug, 37(7-8), 261 - 4
White piedra and Trichosporon species in equatorial Africa . III . Identification of Trichosporon species by slide agglutination test; Douchet C et al.; Fifty-two Trichosporon strains isolated from Gabonese female patients 15-60 years, were studied . The identity of these strains was established by two different methods: the method proposed by Gueho et al . (1992), based on mycological criteria, and a slide agglutination method performed with monospecific antisera prepared in our laboratory . The final results show a perfect correlation between the two methods, which allowed us to identify 25 strains of T . mucoides, 21 strains of T . inkin and seven strains of T . asahii . The results of the agglutination tests performed with 24-h-old subcultures grown on Sabouraud glucose agar are available in less than 15 mins . In the light of these results, it appears that this method, which is rapid and easy to perform and reproduce, may readily be used in hospital laboratories . In addition, this method allowed us to verify the presence of antigens common to the genera Cryptococcus and Trichosporon, which were easily shown by the use of crude sera . The fact that the anti-Trichosporon monospecific sera lose their capacity to agglutinate Cryptococcus neoformans proves their high specificity.

Mycoses, 1994 Jul-Aug, 37(7-8), 243 - 8
Prophylaxis of Candida and Aspergillus infections with oral administration of itraconazole; Van Cutsem J; The broad-spectrum oral triazole antifungal, itraconazole, has been shown to be effective in the treatment of superficial and systemic infections with fungi including Candida albicans, C . krusei and C . glabrata, Cryptococcus, Aspergillus, Histoplasma, Blastomyces and others . Its broad spectrum of activity, high and persistent tissue levels and favourable safety profile suggest that it may be appropriate for the prevention of opportunistic fungal infections in at-risk patients . In this study, itraconazole's prophylactic efficacy was tested against experimental models of Candida and Aspergillus infection . A single dose of 1.25 mg kg-1 or 2.5 mg kg-1, given 1 h before vaginal infection with C . albicans, protected 50% of treated rats . In systemic and disseminated candidosis, prophylaxis with itraconazole reduced both folliculitis and organ Candida content in guinea pigs . Amphotericin B was also used in this study and was found to be less efficacious than itraconazole . Itraconazole prolonged survival when administered to guinea pigs before experimental induction of systemic and invasive aspergillosis . In all cases, increasing the itraconazole dosage increased its prophylactic efficacy . Therefore, as the clinical efficacy of itraconazole is accurately reflected by the results of animal models, this study shows itraconazole to be a potential prophylactic therapy for patients at risk of opportunistic fungal infection.

Mycoses, 1994 Jul-Aug, 37(7-8), 229 - 33
One hundred years ago: the history of cryptococcosis in Greifswald . Medical mycology in the nineteenth century; Knoke M et al.; Medico-mycological investigations began at Greifswald in Germany as early as 1842 when Wilhelm Baum (1799-1883) was appointed to the chair of surgery of the university . This is shown by some theses of the time, as well as by the discovery of the contagious nature of pityriasis versicolor by Carl Ferdinand Eichstedt (1816-92), who identified a fungus as the cause (1846), later named Microsporon furfur (C . Robin 1853) . In 1868 the physician Karl Friedrich Mosler (1831-1911) published clinical-mycological studies and investigations about animal feeding with yeasts . Some time later (1870) Friedrich Grohe (1830-86) and his assistants, Alwin R.A . Block (1843-?) and M.R . Roth of the Pathological Institute, described the results of transmission studies with 'Aspergillus glaucus, Penicillium glaucum and yeast' . His successor in the chair, Paul Grawitz (1850-1932), also published the results of his own mycological investigations . Finally, on 7 July 1894, at an evening lecture of the Greifswald Medical Society, Abraham Buschke (1868-1943) from the Hospital of Surgery gave a talk 'on a peculiar disease caused by coccidia', which was followed by a talk by the pathologist Otto Busse (1867-1922) on a 'demonstration of a pathogenic coccidia species' . Busse's subsequent publications are the first proper descriptions of cryptococcosis (1894 ff.) . However, Cryptococcus neoformans was named after F . Sanfelice, whose results were published later (1895).

Indian J Chest Dis Allied Sci, 1994 Jul-Sep, 36(3), 153 - 8
Resolution of cryptococcal meningitis and associated granuloma lung with antifungal therapy: report of a case; Ray D et al.; A 49-year-old diabetic male had been unsuccessfully treated with antitubercular therapy for a granulomatous lesion of the left lung detected elsewhere nine months ago . He presented with evidence of meningitis which was found to be due to infection with Cryptococcus neoformans . Both the meningeal and lung lesions resolved after 6 weeks of combined therapy with amphotericin B and flucytosine . The report of the case along with a brief review of the relevant literature is presented.

Gene, 1994 Jun 24, 144(1), 103 - 6
Characterization of the CNRE-1 family of repetitive DNA elements in Cryptococcus neoformans; Spitzer SG et al.; The pathogenic yeast Cryptococcus neoformans contains 10-20 dispersed repetitive elements that hybridize to clone CNRE-1.0 . Screening of a genomic library with probes derived from CNRE-1.0 identified five phages with restriction maps that overlapped CNRE-1.0 and three additional phages that belonged to two distinct groups . Sequencing of internal 3.5-kb SstI fragments from two CNRE-1-like elements revealed 95% homology, as well as a conserved open reading frame . A PCR-RFLP assay was developed that can distinguish different subfamilies of CNRE-1-like elements.

Med Klin (Munich), 1994 Jun 15, 89(6), 299 - 304
{Systemic fungal infections in hematologic neoplasms . An autopsy study of 1,053 patients}; Pfaffenbach B et al.; BACKGROUND: Mycoses are common complications of haematological neoplasias . For successful antimycotic treatment, a knowledge of preferential underlying disease, frequency, species and site of the mycosis is of importance . PATIENTS AND METHODS: Postmortem material comprising clinical data, autopsy protocols and histological sections obtained between 1976 and 1990 from 1,053 patients with leukaemia and malignant lymphomas following antineoplastic therapy was analysed retrospectively . RESULTS: Autopsy revealed systemic mycoses in 184 patients (17.5%) . Between 1976 and 1990, the incidence of fungal infections increased from 12% to 30%, most being found in acute leukaemia (24%) . Myeloproliferative syndrome (18%), non-Hodgkin's lymphomas (16%), Hodgkin's disease (10%) and plasmocytoma (2.5%) were less frequently associated with mycoses . With no preference for any particular malignancy in evidence, aspergillosis predominated at histology (85 cases), while candidosis occurred in 75 cases . A combination of two mycoses (aspergillosis and candidosis) (14 patients), zygomycosis (eight patients) and cryptococcosis (two patients) were much less common . While aspergillosis caused mostly pulmonary (81 cases) and cerebral (18 cases) infections, candidosis most frequently affected the GI tract (83 cases) . The fungal infection was regarded as the main cause of death in some 76% of the cases . An analysis of bone marrow of patients with mycosis (184 cases) revealed a predominance of hypoplasia (54%) over tumour infiltration (34%) and normal bone marrow (12%) . In malignancies with no mycoses (869 cases) in contrast, hypoplasia was significantly less common (19%) than infiltration (59%) or normal bone marrow (22%) (p < 0.001) . CONCLUSION: The incidence of mycoses in haematological neoplasias in our post mortem series has continued to increase . Bone marrow hypoplasia in particular predisposes to fungal infection . The lungs are the organs of predilection, and aspergillosis is likely to be the infection presenting.

Ann Intern Med, 1994 Jun 1, 120(11), 932 - 44
Prophylaxis for opportunistic infections in patients with HIV infection; Gallant JE et al.; OBJECTIVE: To review the efficacy of chemoprophylaxis for opportunistic infections in persons infected with human immunodeficiency virus (HIV) . DATA SOURCES: English-language articles on the prevention of HIV-related opportunistic infections were identified through MEDLINE (1985 to 1993) and through review of abstracts presented at the International Conferences on AIDS, the Interscience Conferences on Antimicrobial Agents and Chemotherapy, and the National Conference on Human Retroviruses and Related Diseases . STUDY SELECTION: Importance was assigned in descending order to controlled clinical trials, uncontrolled trials and retrospective studies, and prospective observational studies . DATA SYNTHESIS: Persons infected with HIV who are at risk for Pneumocystis carinii pneumonia should receive prophylaxis, preferably with trimethoprim-sulfamethoxazole . Alternative agents are aerosolized pentamidine, dapsone, and dapsone-pyrimethamine . Patients who are seropositive for Toxoplasma gondii may benefit from primary prophylaxis against toxoplasmosis using trimethoprim-sulfamethoxazole or dapsone-pyrimethamine . Life-long secondary prophylaxis is indicated for all patients previously treated for toxoplasmic encephalitis . Long-term suppressive therapy is required for all patients with cryptococcal meningitis and histoplasmosis, and many patients with recurrent mucosal candidiasis also benefit from long-term suppression . The role of primary prophylaxis of fungal infections, however, is uncertain . Rifabutin has been approved to prevent disseminated infection with Mycobacterium avium complex and is indicated for all patients with CD4 counts less than 100/mm3 . Chemoprophylaxis with isoniazid for 12 months is indicated in all patients infected with HIV who have or are at high risk for M . tuberculosis infection . No effective primary prophylactic agent is available for cytomegalovirus disease, although several investigational drugs are being studied . Acyclovir is effective in decreasing recurrences of herpes simplex virus infection . The incidence of common bacterial infections is decreased by trimethoprim-sulfamethoxazole . Pneumococcal polysaccharide vaccine is recommended for adult patients infected with HIV, and Haemophilus influenzae type b conjugate vaccine is recommended for children infected with HIV . CONCLUSIONS: A growing number of infections related to the acquired immunodeficiency syndrome are preventable with currently available agents . Issues of drug interactions, toxicity, and cost-effectiveness will become increasingly important in the management of patients with advanced HIV disease.

Infect Dis Clin North Am, 1994 Jun, 8(2), 383 - 98
Cryptococcosis; White MH et al.; Cryptococcal disease is the most common life-threatening fungal infection in patients with AIDS . The most common manifestation, meningitis, has an indolent presentation that may lead to a delay in diagnosis . Although clinical trials have demonstrated efficacy with fluconazole in some patients, amphotericin B, with or without flucytosine, is the treatment of choice . Lifelong suppression of cryptococcal disease after initial therapy, however, is best achieved with fluconazole . Prognostic staging systems and primary prophylaxis of cryptococcal disease are also discussed.

Br J Biomed Sci, 1994 Jun, 51(2), 100 - 3
Differentiation of Cryptococcus neoformans serotypes A and D using creatinine dextrose bromothymol blue thymine medium; Irokanulo EA et al.; A serotype differentiation of the encapsulated yeast Cryptococcus neoformans is described using creatinine dextrose bromothymol blue thymine (CDBT) medium . On CDBT medium C . neoformans serotype D grew as bright red colonies, turning the medium a bright orange after five days incubation at 28 degrees C . C . neoformans serotype A grew as pale colonies with no apparent colour effect on the medium . Serotypes B and C caused a slight greening of the medium . The reaction of the four serotypes of C . neoformans on CDBT medium is considered useful in the differentiation of the closely related serotype A and D.

Q J Med, 1994 Jun, 87(6), 343 - 9
Cryptococcal meningitis (C . neoformans var . gattii) leading to blindness in previously healthy Melanesian adults in Papua New Guinea; Lalloo D et al.; Cryptococcal meningitis is a common cause of chronic meningitis in Papua New Guinea, affecting apparently immunocompetent people . The majority of infections are believed to be due to Cryptococcus neoformans var . gattii . We have reviewed the records of 49 Melanesian adults who presented with proven cryptococcal meningitis to the University teaching hospital in Port Moresby, and compare our findings with other published studies of cryptococcal meningitis in the tropics and sub-tropics . None of the patients had an obvious cause of immunosuppression . Visual disturbances and fundoscopic changes of papilloedema or papillitis were particularly common . The in-hospital case fatality rate for patients treated with amphotericin B and flucytosine was 22.4% . Of the fully treated patients, 31% became completely blind before being discharged from hospital . Therapy directly aimed at reducing intracranial pressure may improve outcome.

FEMS Microbiol Lett, 1994 Jun 1, 119(1-2), 105 - 10
Microcin production by the yeast Cryptococcus humicola; Golubev W et al.; Cryptococcus humicola strains secrete killer toxins inhibitory (at pH values ranging from 3 to 5.5) to many ascomycetous and basidiomycetous yeast-like fungi . RNA or DNA plasmids were not detected in the killers . The amino acid-containing toxins were of low M(r), soluble in methanol, resistant to proteolysis, thermostable, cellophane-diffusible and were specified as microcins . These findings show that the killer phenomenon in yeasts such as bacteriocinogeny may be due to excretion of two types of killer toxins: mycocins and microcins.

Am J Respir Crit Care Med, 1994 Jun, 149(6), 1591 - 6
Pulmonary disease associated with the human immunodeficiency virus in Kigali, Rwanda . A fiberoptic bronchoscopic study of 111 cases of undetermined etiology; Batungwanayo J et al.; All human immunodeficiency virus type 1 (HIV-1) infected adult patients referred to the Division of Pulmonary Diseases of the Centre Hospitalier de Kigali, Rwanda for evaluation of a pulmonary disease of undetermined etiology (PDUE) were investigated by fiberoptic bronchoscopy using both bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB) . During a 10-mo period 111 HIV-1 infected patients with PDUE were examined, of whom 47 (42%) fulfilled the World Health Organization (WHO) clinical case definition for acquired immunodeficiency syndrome (AIDS) and seven (6%) had an AIDS-defining illness . Nonspecific interstitial pneumonitis was diagnosed in 42 (38%) patients, tuberculosis in 25 (23%), cryptococcosis in 14 (13%), Kaposi's sarcoma (KS) in 10 (9%), Pneumocystis carinii pneumonia (PCP) in five (5%) . The diagnosis remained undetermined in 18 (16%) patients . Chest radiograph patterns were generally nonspecific . TBB and BAL had diagnostic yields of 82 and 26% of all final diagnoses, respectively . Our study on Rwandese HIV-1-infected patients with PDUE provides evidence for a large spectrum of pulmonary diseases with relative frequencies differing strikingly from those in developed countries . Detailed investigations confirm the rarity of PCP in Africa and highlight nonspecific interstitial pneumonitis as the predominant diagnosis of PDUE . Empiric antituberculosis treatment is justified in the absence of clinical manifestations suggestive of a specific diagnosis and while awaiting the results of the diagnostic procedures . Primary prophylaxis for PCP would not be appropriate in Africa.

Singapore Med J, 1994 Jun, 35(3), 294 - 7
Warning symptoms of sinister headache; Tan AK et al.; Headache is a common complaint . In most patients, it is usually a problem of migrainous or tension-type headache . It is crucial that a physician is able to differentiate sinister causes of headache from the more benign ones . Six cases are presented to illustrate the fact that there are clues in the history to suggest a sinister cause of headache even though there are minimal or no neurological deficits on physical examination . At some point of time, these cases were examined by a senior physician but they were diagnosed as migrainous or tension-type headaches . The first case is a 41-year-old labourer with cryptococcal meningitis . He presented with severe headaches at a relatively late age . A 20-year-old female complained of the worst headache she ever had and this was due to a subarachnoid haemorrhage . The third case was a young woman with a large parietal meningioma . Her headaches had recently assumed a different character . The fourth case involved an investment manager who developed headaches with transient diplopia and projectile vomiting and investigations revealed an ependymoma . A shipyard worker complained of a constant headache which disturbed his sleep . Two weeks after medical consultation, the character of his headache changed and he developed diplopia in all directions of gaze . He succumbed to pituitary apoplexy . The final case is a 28-year-old woman who had a complicated migraine . CT scan of the brain showed a large arterio-venous malformation.

J Chemother, 1994 Jun, 6(3), 173 - 6
Comparison of broth dilution and semisolid agar dilution for in vitro susceptibility testing of Cryptococcus neoformans; Del Poeta M et al.; We compared the in vitro activity of amphotericin B, flucytosine, itraconazole, fluconazole, ketoconazole and miconazole against 18 strains of Cryptococcus neoformans by using two methods: microbroth dilution and semisolid agar dilution . By both of the methods minimum inhibitory concentrations (MICs) showed a wide range for all antifungal agents but not for amphotericin B . Statistically significant differences between the two methods were observed only with amphotericin B and flucytosine, p = 0.048 and p = 0.045 respectively . Our study suggests that azole susceptibility testing for C . neoformans may be performed by the broth microdilution as well as the semisolid agar test . The choice of the method when testing amphotericin B and flucytosine is more problematic.

Rinsho Shinkeigaku, 1994 Jun, 34(6), 596 - 8
{A case of cryptococcal meningoencephalitis, which damaged the medial part of the temporal lobe and caused gradually progressing memory disturbance}; Nakamura K et al.; A 71-year-old female was admitted to the National Cardiovascular Center, complaining of memory disturbance that had been gradually worsening for about two years . Neurologically, except for the memory disturbance, higher brain functions were almost normal and there were no signs of meningeal irritation . A cerebrospinal fluid examination showed lymphocytic dominant pleocytosis, elevated protein levels and decreased glucose levels . Furthermore, Cryptococcus neoformans was detected in the cerebrospinal fluid . A brain CT demonstrated a low density area at the medial part of the left temporal lobe . This lesion appeared as a low intensity area in the T1 weighted image, and as a high intensity area in the T2 weighted image in MRI, and was enhanced by the administration of Gadolinium-DTPA . After administration of fluconazole, improvements were observed in cerebrospinal fluid findings and the enhancement effect of Gadolinium-DTPA in MRI also became unclear on the lesion inside the left temporal lobe . No worsening of the memory disturbance was observed . It was presumed that the gradually progressive memory disturbance had been triggered by the cryptococcus-caused meningoencephalitis, in particular the damage at the medial part of the temporal lobe.

Mycopathologia, 1994 Jun, 126(3), 147 - 55
Clinico-pathological studies on experimental cryptococcal mastitis in goats; Singh M et al.; Unilateral intramammary inoculation of 10 goats with Cryptococcus neoformans (2 x 10(6) yeast cells) resulted in the development of mastitis, with gross and microscopic lesions being restricted to the infected udder halves only and there was no dissemination of infection to the opposite uninfected udder halves as well as to other organs of the body . The experiment was continued for 40 days, with 2 animals each from the infected and control groups being killed on 5th, 10th, 20th, 30th and 40th day post-inoculation (DPI) . Initial enlargement of the infected udder halves was followed by marked decrease in size leading to very small, firm and nodular udder halves . After infection, there was also sharp fall in the milk yield . Cryptococcal organisms were demonstrated in the mastitic milk and udder impression smears with special stains . C . neoformans was reisolated from the milk of the only infected udder halves up to 25th DPI . Microscopically, there was initially acute diffuse purulent mastitis which later on became chronic, characterised by marked infiltration of lymphocytes, macrophages, extensive fibrosis and development of multiple granulomas . The cryptococcal organisms could be demonstrated in the udder sections only up to 30th DPI . It is concluded that intramammary inoculation of Cryptococcus neoformans in goats leads to severe mastitis with sharp fall in milk yield.

Indian J Ophthalmol, 1994 Jun, 42(2), 51 - 63
Acquired immunodeficiency syndrome and its ocular complications; Rao NA; Human immunodeficiency virus infection is the first major pandemic of the 20th century . At present, almost 10 million people are known to be infected with this virus, and it is estimated that by the year 2000, approximately 40 million people will be infected . Transmission of this deadly infection is predominantly by sexual contact . Individuals infected with this virus pass through several predictable stages with progressive decrease in circulating CD4+ T cells . During the advanced stage, these patients develop various opportunistic infections or malignancies, or both . It is this advanced stage that was first recognized as AIDS, which has a 100% mortality rate . The opportunistic organisms that can involve the eye in patients with AIDS include cytomegalovirus, herpes zoster, Toxoplasma gondii, Mycobacterium tuberculosis, Cryptococcus neoformans, Mycobacterium avium-intracellulare, Pneumocystis carinii, Histoplasma capsulatum, Candida, and others . Intraocular lesions from these agents often represent disseminated infections . Visual morbidity occurs secondary to retinitis due to cytomegalovirus, herpes zoster, or Toxoplasma gondii . Anti-viral agents such as ganciclovir or foscarnet are effective against cytomegalovirus infection . The role of the ophthalmologist in the diagnosis and management of AIDS is becoming increasingly important . Not only does the eye reflect systemic disease, but ocular involvement may often precede systemic manifestations . In the AIDS patient, the ophthalmologist thus has an opportunity to make not only a slight-saving, but also life-saving diagnosis of disseminated opportunistic infections.

Drug Saf, 1994 Jun, 10(6), 439 - 54
Adverse effects of drugs used in the management of opportunistic infections associated with HIV infection; Peters BS et al.; Pneumocystis carinii pneumonia (PCP) is one of the most common AIDS-defining diagnoses . First-line therapy is cotrimoxazole (trimethoprim-sulfamethoxazole), despite a high incidence of toxic effects, and a greater incidence of hypersensitivity reactions among HIV-positive patients compared with the seronegative population . Alternative agents such as intravenous pentamidine, or clindamycin with primaquine, and trimethoprim with dapsone, also have a wide range of serious adverse effects, but remain treatment options . Atovaquone appears promising for the treatment of both PCP and toxoplasmosis, and has a lower reported incidence of toxicity than the alternative agents . The most toxic antifungal drugs are reserved for serious infections, such as cryptococcal meningitis . Liposomal amphotericin B has less renal toxicity than standard formulations, and exemplifies that new formulations of existing drugs, although often expensive, may have a better adverse effect profile . There are 2 different drugs currently available for cytomegalovirus (CMV) infections, ganciclovir and foscarnet . Both have a high incidence of serious adverse effects; ganciclovir mainly causes bone marrow toxicity and foscarnet leads to renal toxicity . The drugs used for mycobacterial infection (including mycobacteria as well as tuberculosis) have a wide range of adverse effects, particularly skin rashes and drug-induced hepatitis . Some of these compounds are quite new, such as rifabutin and clarithromycin, and it is important to be ever vigilant for previously unreported adverse effects.

Mycoses, 1994 Jun-Jul, 37(5-6), 187 - 90
Trends and sources of nosocomial fungaemia; Taylor GD et al.; Concurrent surveillance of blood culture isolates in a 1000-bed tertiary care hospital over a 7-year period from 1986 to 1993 identified 102 episodes of nosocomial fungaemia, representing 6.6% of all episodes of nosocomial bloodstream infections and 0.49/1000 admissions . No significant change in the frequency, rate, source or microbial aetiology of nosocomial fungaemia occurred over the 7-year period . Candida albicans accounted for 74%, followed by Candida (Torulopsis) glabrata (8%), C . parapsilosis (7%), C . tropicalis (3%), C . lusitaniae (2%), C . krusei, Malassezia furfur Saccharomyces cerevisiae, Hansenula anomala and Cryptococcus albidus (one each) . 'Primary' fungaemia, usually attributed to intravascular catheters, was considered to be the source in 65% of cases, with 64% of these patients receiving total parenteral nutrition (TPN) . Other important sources of infection included the urinary tract (11%), the gastrointestinal tract (8%) and the respiratory tract (7%) . Sixty-four % of patients were in one of the hospital's seven intensive care units (ICUs) when their infection developed, the neonatal ICU and adult medical/surgical ICU each accounting for 21% . Only 7% of cases were associated with neutropenia and another 14% with malignancy or immunosuppression . Death occurred within 7 days of diagnosis of fungaemia in 23 cases . In eight instances, fungaemia was considered the main cause of death . We conclude that in our hospital nosocomial fungaemia is largely caused by C . albicans, occurring in association with intravascular catheter use and TPN in ICU patients . Most cases are not associated with recognized immune defence defects . Fungaemia is associated with a high short-term mortality rate.

Mycoses, 1994 Jun-Jul, 37(5-6), 155 - 60
Comparative stability, sensitivity and specificity studies with different lots of Blastomyces dermatitidis yeast and mycelial lysate antigens; Orr ML et al.; Comparative studies were performed to assess the stability and lot-to-lot variation of Blastomyces dermatitidis yeast and mycelial phase lysate antigens . Four lots were prepared from each growth phase of B . dermatitidis strain T-58 (canine isolate) during a 14-month period . Serum specimens from dogs with blastomycosis, histoplasmosis, coccidioidomycosis, cryptococcosis and aspergillosis were assayed for antibody content using an alkaline phosphatase enzyme-linked immunosorbent assay (ELISA) . The four lots of the yeast phase reagents were similar with respect to sensitivity and specificity, and the absorbance readings were approximately four times greater with sera from dogs with blastomycosis than with histoplasmosis or coccidioidomycosis . Even less cross-reactivity was evidenced when the sera from dogs with cryptococcosis and aspergillosis were assayed . In contrast, the four lots of the mycelial lysate reagents were considerably less reactive and more cross-reactive than the yeast phase antigens and, as above, the four reagents retained their activity after prolonged storage . Therefore the results indicated that the lysate antigens exhibited a great deal of stability and lot-to-lot variations in activity were not observed.

J Med Assoc Thai, 1994 Jun, 77(6), 322 - 6
Disseminated cryptococcosis presenting as molluscum-like lesions in three male patients with acquired immunodeficiency syndrome; Chiewchanvit S et al.; Cryptococcosis is an opportunistic infection caused by a ubiquitous encapsulated yeast, Cryptococcus neoformans . The pulmonary infection is primary site and most frequently self-limited and may be asymptomatic . The most common recognized site of disseminated cryptococcosis is the central nervous system . The cutaneous cryptococcosis is rare and nonspecific . More recently, in patients with AIDS, some cases of cutaneous cryptococcosis resembling molluscum contagiosum have been described and occasionally appeared before systemic signs and symptoms . To our knowledge, this has not previously been reported in Thailand . This is a report of 3 males with acquired immunodeficiency syndrome who developed disseminated cryptococcosis with cutaneous lesions resembling molluscum contagiosum . Skin findings in disseminated cryptococcosis indicate a poor prognosis, however, earlier recognition and treatment would improve survival.

Jpn J Med Sci Biol, 1994 Jun, 47(3), 141 - 56
Specific detection of Aspergillus and Penicillium species from respiratory specimens by polymerase chain reaction (PCR); Makimura K et al.; A polymerase chain reaction (PCR) method capable of detecting both Aspergillus fumigatus infections, pulmonary non-fumigatus Aspergillus species (spp.) and Penicillium spp . from clinical specimens was established . The primer pair was designed on the basis of the sequence of the 18S-ribosomal RNA gene of A . fumigatus and P . notatum . A 385 bp product was successfully amplified by this PCR method from all of 12 medically important Aspergillus spp . and Penicillium spp . (38 strains), but not from human, calf, Escherichia coli, methicillin-resistant Staphylococcus aureus (MRSA), any of 14 medically important yeastlike fungal species tested (32 strains) including Candida albicans, several non-albicans Candida and Saccharomyces cerevisiae, Cryptococcus neoformans, Mucor spp . or Pneumocystis carinii . This specificity was subsequently confirmed by Southern hybridization analysis . The established PCR can detect such a small amount as 1 pg of A . fumigatus DNA by staining the PCR product with ethidium bromide . With sputum specimens from clinically diagnosed aspergilloma patients, this PCR technique was demonstrated to be a more sensitive diagnostic method for Aspergillus infections than conventional culture techniques.

Arch Intern Med, 1994 May 9, 154(9), 1032 - 4
Disseminated cutaneous cryptococcosis . Comparison of clinical manifestations in the pre-AIDS and AIDS eras; Pema K et al.; A review of the literature suggests some differences in the cutaneous manifestations of cryptococcosis present in patients in the pre-acquired immunodeficiency syndrome (AIDS) era compared with those manifestations that are present in today's AIDS era . In both periods, cutaneous manifestations can precede and be the sole clue to disseminated cryptococcal infection . Today, cutaneous cryptococcal involvement is often mistaken for molluscum contagiosum or Kaposi's sarcoma . We describe a patient with disseminated cryptococcosis who presented with skin lesions mimicking molluscum contagiosum, and who was subsequently shown to have AIDS.

Radiol Med (Torino), 1994 May, 87(5 Suppl 2), 52 - 61
{Abdominal manifestations in immunocompromised patients}; Cornalba GP et al.; Abdominal infections or tumors in the immunocompromised host are both common in AIDS but uncommon in transplant recipients . The role of diagnostic imaging modalities differs in the patients with specific symptoms such as dysphagia, diarrhea, malabsorption and jaundice and in the patients with aspecific clinical findings such as fever, weight loss, superficial lymphadenopathies and abdominal pain . In the former patients, the symptoms suggest a disease of one or more alimentary tracts, in which case radiology is ancillary to clinics and endoscopy plays the leading role to make the diagnosis . However, X-ray barium studies yield valuable information on different types of infections--e.g., Candida, Cytomegalovirus, mycobacterium avium intracellulare and Cryptococcus infections--in Kaposi's sarcoma and in gastrointestinal lymphoma . In these cases CT findings may suggest the diagnosis . In the patients with aspecific findings, US, as an easy immediate examination, and CT, as a panoramic means, can demonstrate deep lymphadenopathies and focal parenchymal lesions which are sometimes suspected to be abscesses or tumors . Moreover, both methods can provide indications and guide to percutaneous needle biopsies . Especially CT findings can distinguish mycobacterial infections from neoplastic lesions on the basis of the involved anatomical sites and of densitometric features . US and CT are useful means to monitor HIV+ subjects, to manage AIDS patients and to follow-up transplant recipients.

Kansenshogaku Zasshi, 1994 May, 68(5), 612 - 6
{Fungal infection in hepatobiliary and pancreatic diseases: clinical evaluation in autopsy cases}; Yamamoto S et al.; A clinical assessment of fungal infection in hepatobiliary and pancreatic diseases during 1975 and 1991 was made and 25 cases of systemic mycosis were noted . Among 25 cases there were 20 liver diseases (hepatocellular carcinoma 12, liver cirrhosis 5, fulminant hepatitis 2, polyarteritis nodosa 1), 2 cases of gallbladder cancer and 3 cases of pancreatic cancer . The fungus was consisted of 14 cases (56%) of Candida, 9 cases of Aspergillus (36%), and 2 cases of Cryptococcus (8%) . Fungal infection was most frequent in the lung (8 cases) and esophagus (6 cases), but rarely in the stomach, lymph node, liver, thyroid, kidney and gallbladder . Generalized fungus infection was noted in four cases (16%) . Fatal fungal infection was complicated in liver cirrhosis (2 cases), fulminant hepatitis (one case), gallbladder cancer (one case) and cystadenocarcinoma of the pancreas (one case) . In five fatal cases three cases of Aspergillus pneumonia and two cases of Candida septicemia were included . Glucocorticoid was used in 13 cases (52%) and anti-cancer drugs was administered in two cases (12%) . However, in 9 cases (36%) without treatment of glucocorticoid or anti-cancer drug fungal infection was detected . In conclusion, there is a possibility of fungal infection in grave hepatic diseases and empirical administration of anti-fungal agent may be necessary.

Kyobu Geka, 1994 May, 47(5), 417 - 9
{A case of pulmonary cryptococcosis diagnosed by percutaneous lung biopsy}; Arano Y et al.; A 53-year-old male was admitted with complaint of bloody sputum . The chest X-ray film revealed a solitary round mass with cavity formation in the left upper lung field . A diagnosis of pulmonary cryptococcosis was made by the percutaneous lung biopsy . As his chest X-ray film did not improve even by administration of antimycotic agents for 6 months, he underwent partial resection of left upper lobe . Thus, the percutaneous lung biopsy was a significant procedure for the definitive diagnosis of this case.

Acta Cytol, 1994 May-Jun, 38(3), 459 - 62
Fine needle aspiration cytology of peripheral lymph node cryptococcosis . A report of three cases; Alfonso F et al.; Aspiration cytology of lymph nodes allows rapid diagnosis of disseminated cryptococcosis . Three cases of lymph node cryptococcosis diagnosed by aspiration cytology in three patients with acquired immunodeficiency syndrome are presented . The organisms were easily seen with a routine modified Wright and Papanicolaou stain as variably sized yeasts, 5-15 microns in greatest diameter, with thick capsules . Many of the organisms showed narrow base budding . In one case occasional pseudohyphae were observed . The diagnoses were confirmed easily with mucicarmine stain.

Acta Cytol, 1994 May-Jun, 38(3), 427 - 30
Initial diagnosis of disseminated cryptococcosis and acquired immunodeficiency syndrome by fine needle aspiration of the thyroid . A case report; Kaw YT et al.; Fine needle aspiration of the thyroid was performed on a patient with an enlarged, solid gland, revealing numerous budding yeasts of Cryptococcus neoformans . Special stains and culture confirmed the organism . This unexpected finding led to the diagnosis of disseminated cryptococcosis and human immunodeficiency virus infection.

Laryngoscope, 1994 May, 104(5 Pt 1), 566 - 70
Treatment of aphthous ulcers in AIDS patients; Friedman M et al.; From 1987 to 1992, 240 acquired immunodeficiency syndrome (AIDS) patients with oral, laryngeal, and pharyngeal ulcers were evaluated . In 180 patients, ulcers resolved in less than 2 weeks without treatment . Of the 60 patients whose ulcers persisted for more than 2 weeks, 24 were culture positive for herpes simplex virus, Cryptococcus organisms, cytomegalovirus, or Mycobacterium organisms and were treated accordingly . The remaining 36 patients were diagnosed as having major aphthous ulcers . The usual sites for these ulcers were the floor of the mouth, tonsillar fossa, and epiglottis . The most common symptoms were pain and weight loss . The patients were treated with intralesional injection with triamcinolone acetonide and examined weekly . Ulcers were reinjected biweekly as needed . Response to treatment was evaluated by pain relief, ulcer healing, and weight gain . All patients reported pain relief within 2 days of initial injection . Most had marked reduction in ulcer size and subsequent weight gain, and many experienced total resolution of symptoms and complete healing.

J Med Microbiol, 1994 May, 40(5), 358 - 64
Detection of a wide range of medically important fungi by the polymerase chain reaction; Makimura K et al.; A polymerase chain reaction (PCR) method was developed that was capable of detecting a wide range of medically important fungi from clinical specimens . The primer pair was designed in conserved sequences of 18S-ribosomal RNA genes shared by most fungi . The lower limit of detection of this PCR technique was 1 pg of Candida albicans genomic DNA by ethidium bromide staining and 100 fg after Southern analysis . A 687-bp product was amplified successfully by PCR from all 78 strains of 25 medically important fungal species studies, including Candida spp., Hansenula spp., Saccharomyces cerevisiae, Cryptococcus neoformans, Trichosporon beigelii, Malassezia furfur, Pneumocystis carinii, Aspergillus spp., and Penicillium spp., but not from any strains of Mucor spp., Escherichia coli, or methicillin-resistant Staphylococcus aureus (MRSA), calf thymus or human placenta . This specificity was subsequently confirmed by Southern analysis . PCR analysis of blood specimens collected from mice systemically infected with C . albicans and clinical samples including blood, cerebrospinal fluid and sputum appeared to be a more sensitive diagnostic method for invasive fungal infections than a conventional blood culture technique.

J Am Acad Dermatol, 1994 May, 30(5 Pt 2), 844 - 8
Cutaneous involvement with Cryptococcus neoformans in AIDS; Durden FM et al.; Patients infected with HIV are susceptible to many opportunistic fungal infections . Cryptococcus neoformans infection is particularly common in patients with AIDS . We describe a patient with disseminated cryptococcosis resembling molluscum contagiosum and review the typical cutaneous manifestations of disseminated cryptococcosis . A synopsis of case reports in the English literature is also presented.

Infect Immun, 1994 May, 62(5), 1975 - 81
Production of tumor necrosis factor alpha in human leukocytes stimulated by Cryptococcus neoformans; Levitz SM et al.; Tumor necrosis factor alpha (TNF-alpha) is a key mediator of inflammation and may promote human immunodeficiency virus replication in latently infected cells . Since cryptococcosis often is associated with aberrations in the host inflammatory response and occurs preferentially in persons with AIDS, we defined the conditions under which human leukocytes produce TNF-alpha when stimulated by Cryptococcus neoformans . Peripheral blood mononuclear cells (PBMC) produced comparable amounts of TNF-alpha following stimulation with C . neoformans and lipopolysaccharide . Detectable TNF-alpha release in response to C . neoformans occurred only when fungi with small-sized capsules were used and complement-sufficient serum was added . Fractionation of PBMC established that monocytes were the predominant source of TNF-alpha . TNF-alpha gene expression and release occurred significantly later in PBMC stimulated with C . neoformans than in PBMC stimulated with LPS . C . neoformans was also a potent inducer of TNF-alpha from freshly isolated bronchoalveolar macrophages (BAM) . Upon in vitro culture, BAM and monocytes bound greater numbers of fungal cells, yet their capacity to produce TNF-alpha following cryptococcal stimulation declined by 74 to 100% . However, this decline was reversed if the BAM and monocytes were cultured with gamma interferon . These data establish that C . neoformans can potently stimulate TNF-alpha release from human leukocytes . However, several variables profoundly affected the amount of TNF-alpha released, including the type of leukocyte and its state of activation, the size of the cryptococcal capsule, and the availability of opsonins.

Infect Immun, 1994 May, 62(5), 1507 - 12
Polysaccharide antigens of the capsule of Cryptococcus neoformans; Cherniak R et al.; The major significance of the capsular polysaccharide of C . neoformans is its role in potentiating opportunistic infections by the yeast . It has the ability to exert a broad spectrum of influences on the immune response, from activation of phagocytic cells and complement components of the alternative pathway, to the induction of specific antibody, T-suppressor cells, DTH responses, and cytokines (51) . These biological properties along with the serotype specificities are all determined by the physical properties and chemical structures of the polysaccharide antigens that compose the capsule . There is evidence not only for an association of lethal infections with serotype A in patients with advanced AIDS (34, 56), but also for a role for the capsule in directly influencing the infection of CD4+ cells by HIV (57) . Together, these phenomena raise intriguing questions about the possible connection between the chemistry of these capsular antigens and cryptococcal infections in AIDS patients . One speculation is that AIDS creates the optimal physiological conditions for the establishment and spread of cryptococcosis . It has been observed that during the progression of AIDS there is a shift towards a T-2 response (14) . This could lead to conditions that would inhibit the cellular immune responses that block dissemination of cryptococcal infections . Thus, an important consideration in the application of vaccine or immune modulation therapies in the treatment of cryptococcosis in AIDS victims would be the design of vaccines that could boost the T-1 immune response . It has been shown that the form and dose of an antigenic challenge can influence the induction of a T-1 or T-2 immune response (61) . Recently, Murphy has reported that gamma interferon and interleukin 2 are up-regulated in the spleens of mice that produce anticryptococcal TDH and TAMP cells in response to immunogenic doses of cryptococcal culture filtrate antigen given with Freund's complete adjuvant (49) . Perhaps purified cryptococcal antigens (e.g., MP) conjugated to an appropriate carrier or adjuvant could be used in therapeutic strategies to limit cryptococcosis in immunocompromised individuals . Future investigations of virulence and pathogenicity in the context of defined polysaccharide antigens from encapsulated strains of C . neoformans will contribute to a better understanding of the regulation of cryptococcal infection and immunity at the cellular and molecular levels.(ABSTRACT TRUNCATED AT 400 WORDS)

J Infect, 1994 May, 28(3), 319 - 22
Successful treatment of resistant cryptococcal meningitis with amphotericin B lipid emulsion after nephrotoxicity with conventional intravenous amphotericin B; Leake HA et al.; Various formulations have been developed in an effort to reduce the toxicity of amphotericin B . We report a case of cryptococcal meningitis in a 31-year-old HIV-positive man which was successfully treated with amphotericin B lipid emulsion.

J Infect, 1994 May, 28 Suppl 1, 45 - 9
Overview of amphotericin B colloidal dispersion (amphocil); Stevens DA; Amphotericin B colloidal dispersion (ABCD) is an equimolar mixture of amphotericin B and cholesteryl sulphate with desirable preparation and stability characteristics . It allows the intravenous delivery of amphotericin B in doses up to 7 mg/kg daily . Peak serum concentrations of amphotericin B, given as ABCD, are lower, AUC0-infinity similar and half-life longer than deoxycholate amphotericin B . In vitro activity may be altered with respect to the deoxycholate preparation, some isolates being more resistant and others more susceptible . Preclinical toxicology with ABCD revealed a safety factor of five to 19-fold compared with deoxycholate amphotericin B . Animal models of coccidioidomycosis, disseminated cryptococcosis, candidiasis and invasive aspergillosis indicated a better therapeutic ratio, especially in cryptococcosis . Phase I/II studies in humans demonstrate efficacy against coccidioidomycosis, candidiasis and aspergillosis at doses from 1-7 mg/kg/day in at least 100 patients . Renal toxicity was acceptable but infusion-related side effects and anaemia were common . Side effects appear to decrease on therapy . Comparative studies with deoxycholate amphotericin B are needed.

J Infect, 1994 May, 28 Suppl 1, 35 - 43
Liposomal amphotericin B, AmBisome; Hay RJ; The unilamellar liposomal formulation of amphotericin B, AmBisome, is composed of hydrogenated soy phosphatidylcholine, distearoyl phosphatidylglycerol and cholesterol . Early studies of its efficacy in an open design showed that remissions could be induced in candidosis and aspergillosis and that doses of up to 5 mg/kg could be used . Adverse events were infrequent, with the main abnormality seen being hypokalaemia in about 18% of patients . Subsequent developments have extended this work . AmBisome has been used in two open studies of patients with invasive aspergillosis; in one of these remission was achieved in 77% of 17 patients with confirmed infection who had failed to respond to conventional amphotericin B . In AIDS patients with cryptococcosis AmBisome given for 6 weeks at 3 mg/kg daily produced mycological remission of meningitis in 67% . Other infections treated with the drug include zygomycete (mucormycosis) and Fusarium infections . AmBisome has also been used as preventative therapy in bone marrow transplant recipients and was found to reduce fungal colonisation rates . There were fewer systemic fungal infections in the treated versus placebo groups although this did not achieve statistical significance . Lack of renal and liver toxicity or anaemia has been confirmed in subsequent studies . In addition febrile reactions to the AmBisome are rare . The drug has also been used effectively in children, including infants, with systemic fungal infections . In visceral leishmaniasis patients, including HIV positive individuals, remissions have been obtained using drug regimens of 1-2 mg/kg of 2.1 days and 3 mg/kg for 10 days.

Clin Infect Dis, 1994 May, 18(5), 789 - 92
Measurement of cryptococcal antigen in serum and cerebrospinal fluid: value in the management of AIDS-associated cryptococcal meningitis; Powderly WG et al.; The value of monitoring titers of cryptococcal antigen in serum and cerebrospinal fluid (CSF) during therapy for AIDS-associated cryptococcal meningitis was evaluated . Baseline and final titers of antigen in serum and CSF from participants in two studies of such therapy were categorized as increased (a rise of at least two dilutions), unchanged, or decreased (a fall of at least two dilutions) . There was no correlation between outcome and changes in serum titers of cryptococcal antigen during treatment for acute meningitis or during suppressive therapy . During therapy for acute infection, an unchanged or increased titer of antigen in CSF was correlated with clinical and microbiological failure to respond to treatment; the correlation was especially strong among patients whose baseline titer of antigen was > or = 1:8 (P = .01) . A rise in CSF antigen titer during suppressive therapy was associated with relapse of cryptococcal meningitis (P < .001) . We conclude that serial monitoring of cryptococcal antigen, as conducted in these studies, has a limited role in the management of AIDS patients with cryptococcal meningitis.

Mycopathologia, 1994 May, 126(2), 65 - 73
Olfactory mucosa response in guinea pigs following intranasal instillation with Cryptococcus neoformans . A histological and immunocytochemical study; Lima C et al.; A central nervous system isolate from an acquired immunodeficiency syndrome (AIDS) patient of 10(3) Cryptococcus neoformans cells was instilled intranasally into guinea pigs . These were killed to evaluate the fate of the organisms and the response of the olfactory mucosa . Olfactory epithelium prevented the penetration of Cryptococcus neoformans and showed focal hyperplastic responses . The organisms, which manifested an affinity for the olfactory portion of the nasal cavities, were cleared from the olfactory space with no intervention from the immune system cells . By the end of the fifth week almost no organisms could be found and there was no histological evidence of dissemination . In contrast, destruction of the olfactory epithelium with zinc sulfate allowed the invasion of the subepithelial tissues, demonstrating the role of the olfactory mucosa in preventing infection with Cryptococcus neoformans through the nasal route . The results and the model described in this report may be useful in clarifying the pathogenic mechanisms of cryptococcosis and the non immune mediated host responses to Cryptococcus neoformans.

J Neurol Sci, 1994 May, 123(1-2), 195 - 9
Olfactory pathways in three patients with cryptococcal meningitis and acquired immune deficiency syndrome; Lima C et al.; The olfactory mucosa, bulbs and tracts were examined for the presence of Cryptococcus neoformans in 3 patients with the acquired immune deficiency syndrome (AIDS) and cryptococcal meningitis . Two of them had antibodies against HIV-1 and one had positive serology for HIV-2 . Cryptococci were seen in the subarachnoid space around olfactory tracts and bulbs and in the submucosal olfactory nerve fascicles . In one case, olfactory nerve fascicles from the lamina propria were also affected . Olfactory epithelium and respiratory mucosa were not involved . We suggest that Cryptococcus reached the olfactory nerve fascicles through the olfactory pathways for cerebrospinal fluid drainage which might serve as a source of latent cryptococcal infection.

J Neurol Sci, 1994 May, 123(1-2), 173 - 9
DNA amplification by the polymerase chain reaction for the rapid diagnosis of tuberculous meningitis . Comparison of protocols involving three mycobacterial DNA sequences, IS6110, 65 kDa antigen, and MPB64; Lee BW et al.; DNA amplification of three Mycobacterium tuberculosis-specific DNA sequences by the polymerase chain reaction (PCR) were evaluated as a means for rapid diagnosis of tuberculous meningitis (TBM) . The DNA sequences amplified were a 123 bp region of the IS6110 insertion elements which occur in multiple copies in the mycobacterial genome, a 240 bp region (nts 460-700) from the MPB 64 protein coding gene, and the 383 bp region of the 65 kDa heat shock protein (HSP) antigen . Twenty-seven cerebrospinal fluid (CSF) specimens were studied . Six were obtained from patients with TBM diagnosed by culture (4/6) or by the patients' response to anti-tuberculous therapy (2/6) . The remaining 21 specimens were obtained from patients with febrile seizures (3/21), aseptic meningitis (3/21), septic meningitis (14/21), and cryptococcal meningitis (1/21), and these served as negative controls . Our results indicate that although the protocols involving the 3 DNA sequences were able to detect TB DNA in the 6 TBM specimens, the main drawback was their extreme sensitivity, thus giving rise to false positive results . In particular, the repeat copy sequence, IS6110, and the 65 kDa HSP gave unacceptably large numbers of false positive results (62% and 33%, respectively).

AIDS, 1994 May, 8(5), 651 - 4
The role of azoles in the treatment and prophylaxis of cryptococcal disease in HIV infection; Nelson MR et al.; OBJECTIVE: To assess the role of azole therapy in the treatment and prophylaxis of cryptococcosis in HIV-seropositive individuals . STUDY DESIGN: Retrospective case review . SETTING: A dedicated HIV unit in London, UK . PATIENTS: Fifty individuals with a positive cryptococcal antigen or culture from any site between 1 January 1985 and 31 December 1992 . RESULTS: Thirty-eight patients initially presented with meningitis and 12 with alternative disease, five of whom subsequently developed meningeal disease . The 12 patients who presented without meningitis received chronic suppressive therapy after the diagnosis of cryptococcal disease . Two patients receiving itraconazole developed meningitis as did three out of four treated with 200 mg fluconazole daily, but none of the six receiving 400 mg fluconazole daily . Treatment of cryptococcal meningitis was successful in 17 of the 19 patients given fluconazole but only three of the six receiving itraconazole . Following successful treatment of meningitis five out of seven patients given itraconazole and five out of seven given 200 mg fluconazole daily relapsed compared with three out of 25 receiving 400 mg fluconazole daily . CONCLUSION: Fluconazole is an effective treatment for cryptococcal meningitis . For prophylaxis following meningitis, a dose of 400 mg fluconazole is the preferred treatment; lower doses are associated with a higher relapse rate.

J Clin Microbiol, 1994 May, 32(5), 1188 - 92
Restriction fragment length polymorphism analysis of Cryptococcus neoformans isolates from environmental (pigeon excreta) and clinical sources in New York City; Currie BP et al.; Restriction fragment length polymorphism analysis of environmental (pigeon excreta) and clinical Cryptococcus neoformans var . neoformans isolates in a limited geographic area distinguished 6 strains among 8 environmental isolates and 12 strains among 17 clinical isolates . Clusters of patients with three strains types accounted for 47% of clinical isolates . Despite this diversity, two strains were shared by environmental and clinical isolates.

Clin Exp Immunol, 1994 May, 96(2), 230 - 7
Activation of macrophages and expansion of specific T lymphocytes in the lungs of mice intratracheally inoculated with Cryptococcus neoformans; Kawakami K et al.; A quantitative and qualitative change in inflammatory cells in the lungs of mice after intratracheal inoculation of heat-killed Cryptococcus neoformans was examined by direct analysis of the pulmonary intraparenchymal leucocytes . Macrophages and T and B lymphocytes increased, peaked at day 7, and then gradually decreased to the basal level . Macrophages were activated 7 days after the inoculation, as indicated by the enhanced expression of MHC class II, intercellular adhesion molecule-1 (ICAM-1) and Fc receptor (FcR), which have been known as their activation markers . T cells were also activated, as indicated by the induction of IL-2 receptor (IL-2R) and the enhanced expression of leucocyte function-associated molecule-1 (LFA-1) and ICAM-1, a pair of adhesion molecules which have also been regarded as T cell activation markers . CD4+ T cells preferentially accumulated in lungs, and proliferated in vitro by stimulation with heat-killed whole yeast cells, suggesting that at least some of the infiltrated T cells expand locally in response to the organisms . These results demonstrate that the activation of macrophages and T cells reactive to C . neoformans is induced in lungs after intratracheal inoculation of heat-killed organisms, and suggest that these cells interact to eliminate organisms more efficiently from the host.

Clin Immunol Immunopathol, 1994 May, 71(2), 203 - 7
Profound and possibly primary "idiopathic CD4+ T lymphocytopenia" in a patient with fungal infections; Seligmann M et al.; A profound and long-lasting reduction in circulating CD4+ T lymphocytes (< 80/microliters) was found in a 37-year-old man (without known risk factors for HIV infection) presenting with recurrent oral candidiasis who subsequently developed cryptococcal meningitis . Infection with HIV was ruled out by serological and virological studies . In vitro and in vivo cell-mediated immunity was severely impaired . Abnormal phenotypic patterns of both CD4+ and CD8+ cells were consistently observed . A systematic family survey revealed in some of his asymptomatic relatives several immunological abnormalities which may point to a genetically based primary immunodeficiency disorder.

J Med Assoc Thai, 1994 May, 77(5), 253 - 6
Treatment of cryptococcal meningitis with combination itraconazole and flucytosine; Chotmongkol V et al.; The results of an open study of the efficacy of itraconazole and flucytosine in 10 patients with cryptococcal meningitis are reported . The outcome revealed eight responding cases (cure in 4 cases and improvement in 4 cases), and two failure cases . One patient had a relapse which responded to amphotericin B and flucytosine . No toxicity was observed.

Acta Cytol, 1994 May-Jun, 38(3), 361 - 6
Cytologic and differential diagnosis of rhinosporidiosis; Gori S et al.; Rhinosporidiosis is a mycotic infection caused by Rhinosporidium seeberi . The fungus occurs in tissues as spherules measuring 0.25-3 mm . The spherules contain endospores . Diagnosis is usually made histologically on biopsy specimens from polypoid lesions on the mucous membranes of the nasopharynx, larynx, trachea, bronchus and conjunctiva . In our experience two cases of rhinosporidiosis were diagnosed by cytology . The cytologic features are typical . On direct examination the spherules are well-circumscribed, globular structures with several endospores within . The spherules show great variability in size, up to 10-fold . The diameter ranges from 30 to 300 microns . Permanent stains for detecting R seeberi are Giemsa, Gridley and toluidine blue . Numerous mycotic infections (Coccidioides immitis, Histoplasma capsulatum, Mucor, Aspergillus, Blastoschizomya capitatus, Paracoccidioides brasilienses, Cryptococcus neoformans) can be definitively diagnosed or strongly suspected on cytology . In immunocompromised patients it is important to commence the diagnostic study on unstained material . By direct examination R seeberi organisms are identified readily by their brown color . Much more information can be gained from material stained with special stains, especially periodic acid-Schiff, in differentiating R seeberi from Coccidioides immitis.

Med Clin (Barc), 1994 Apr 23, 102(15), 566 - 70
{CD4+ lymphocytes and opportunistic infections and neoplasms in patients with human immunodeficiency virus infection}; Miro JM et al.; BACKGROUND: The CD4+ lymphocytes are the principal target cell for the human immunodeficiency virus (HIV) . Their depletion originates a very severe cell immunosuppression, which conditions the appearance of opportunistic infections and neoplasms characteristic of AIDS . The aim of this study was to evaluate whether there is a relation between the degree of cell immunosuppression and the type of opportunistic infections and neoplasms which these patients develop in Spain . METHODS: The CD4+ lymphocyte counts in 400 adults with HIV infection who developed opportunistic infections or neoplasms were retrospectively reviewed (1987-1991) . This determination was carried out during between two months prior to diagnosis of AIDS (CDC, 1987) to one month after such diagnosis . RESULTS: The results allowed opportunistic infections to be classified into three groups according to the grade of immunosuppression: 1) opportunistic infections with more than 0.2 x 10(9) CD4+ lymphocytes/l (45-60% of cases of tuberculosis, esophageal candidiasis and enteritis by Isospora belli); 2) opportunistic infections with 0-0.2 x 10(9) CD4/l (87-100% of the cases of pneumonia by Pneumocystis carinii, encephalic toxoplasmosis, visceral leishmaniasis and enteritis by Cryptosporidium); 3) opportunistic infections with 0-0.1 x 10(9) CD4 lymphocytes/l (70-100% of the cases of systemic cryptococcosis, retinitis by cytomegalovirus, progressive multifocal leukoencephalopathy and infection by Mycobacterium avium-intracellulare) . With respect to the neoplasms, Kaposi's sarcoma was observed in patients with different degrees of immunosuppression . Seventy-five and 80% of the patients with non Hodgkin's lymphoma and primary cerebral lymphoma had less than 0.2 x 10(9)/l and less than 0.1 x 10(9)/l CD4+ lymphocytes, respectively . CONCLUSIONS: The CD4 lymphocyte counts may predict the type of opportunistic infections which patients with the human immunodeficiency virus infection may develop.

J Immunol, 1994 Apr 15, 152(8), 3970 - 9
CD8 cells play a critical role in delayed type hypersensitivity to intact Cryptococcus neoformans; Mody CH et al.; Although cell-mediated immunity is critical for optimal host defense to C . neoformans, the role of T lymphocyte subsets is complex and poorly understood . CD8 cells are important both for optimal host defense against C . neoformans, and for expression of delayed type hypersensitivity (DTH) . Because host defense correlates with the ability to mount a DTH response to C . neoformans, the current studies were performed to determine the mechanism by which CD8 cells participate in DTH . Mice were immunized by the intratracheal route with live C . neoformans, or by the subcutaneous route with heat-killed C . neoformans . Mice were depleted of CD8 cells in vivo by administration of mAb . After challenge with soluble cryptococcal Ag, the DTH response was quantified as footpad swelling . We found that mice depleted of CD8 cells before immunization were unable to express DTH . Mice depleted of CD8 cells after immunization but before challenge also were unable to express DTH . Splenocytes of mice depleted of CD8 cells in vivo, before immunization, failed to transfer DTH to naive, undepleted mice . Immune splenocytes depleted of CD8 cells in vitro also failed to transfer DTH to naive, undepleted mice . These data indicate that CD8 cells were necessary during the challenge and immunizing phases of DTH, and were necessary for expression of DTH . However, CD8 cell depletion did not abrogate DTH in mice immunized with either soluble cryptococcal Ag in complete Freund's adjuvant, or sheep red blood cells, which are mediated by CD4 cells . These data suggest that CD8 cells play a critical role in the cell-mediated immune response to C . neoformans . Based on this information, it may be possible to protect hosts with deficiencies of CD4 cells, such as in AIDS, by designing immunizing strategies for stimulating CD8 cells.

Thorax, 1994 Apr, 49(4), 370 - 8
Tropical respiratory medicine . 1 . Pulmonary infections in the tropics: impact of HIV infection; Daley CL; PIP: Infection with Mycobacterium tuberculosis is so common in tropical areas that the World Health Organization (WHO) estimates more than 75% of the 8-10 million new cases of tuberculosis (TB) annually occur therein . Infection with HIV is also common in the tropics; the WHO estimated in 1992 that 9-11 million adults were infected with HIV, mostly in developing countries . This tropical overlap of HIV infection and pulmonary pathogens makes pulmonary infections a common manifestation of HIV infection, especially TB and bacterial pneumonia . Bacterial pneumonia accounts for at least 25% of medical admissions to one of East Africa's largest hospitals and recent cohort and case-control studies have shown increased rates of disease among HIV-infected individuals . Of all the pulmonary infections encountered in the tropics, however, M . tuberculosis is one of the most significant pathogens . Data from sub-Saharan Africa and Haiti have shown that 17-66% of TB cases are seropositive for HIV-1 . Moreover, 50% of seropositive patients presenting with pulmonary symptoms have TB . This review, however, focuses upon non-tuberculosis pathogens affecting HIV-infected patients in tropical and developing countries . Pneumococcus, nocardiosis, and melioidosis are discussed under bacterial pneumonia and are followed by cryptococcosis, histoplasmosis, paracoccidioidomycosis, and penicillium marneffei under fungal pneumonia . Other sections explore pneumocystis pneumonia, parasitic pneumonia (strongyloidiasis), pleural effusions, and the evaluation of HIV-infected patients with pulmonary disease .

Heredity, 1994 Apr, 72 ( Pt 4), 384 - 95
Genotype-specific habitat selection for oviposition sites in the cactophilic species Drosophila buzzatii; Barker JS et al.; Isofemale lines of the cactophilic species, Drosophila buzzatii, exhibit genetic variation for their oviposition response to cactus yeast species in the laboratory . In general, interactions between yeast species preclude the use of pairwise preferences as predictors of preferences in three-way choice experiments . Two isofemale lines with relatively high laboratory preference for ovipositing on the yeast Pichia cactophila (as opposed to Cryptococcus cereanus) and two isofemale lines with relatively low preference for P . cactophila were used in a series of field release experiments to determine if laboratory preferences were also realized under field conditions . The influence of yeast species on both settling behaviour (long-distance response) and oviposition preference (short-distance response) were tested . The four lines were identical in their settling behaviour, preferring P . cactophila . The analysis of the oviposition preference tests showed significant line effects which correlated with the laboratory results . Thus a genetic component for oviposition preference under laboratory and field conditions was demonstrated and this strengthens the evidence for genotype-specific habitat selection in D . buzzatii . One low line, however, did not differ significantly from the two high lines under field conditions . A laboratory retest of this low line showed that the laboratory preference had not changed . The reason for the difference in the two situations is unknown but undoubtedly is attributable to uncontrolled variables under the field situation . Settling behaviour and oviposition response, in general, appear to be proximately linked to differences in the volatiles produced by the different yeast species.

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