Cryptococci

J Med Vet Mycol, 1993, 31(1), 87 - 9
Cryptococcosis produced by a urease negative strain of Cryptococcus neoformans; Bava AJ et al.; A urease negative strain of Cryptococcus neoformans was isolated form a patient with AIDS . The identification of the yeast was confirmed by physiological and pathogenicity tests . Clinically, the disseminated cryptococcal infection in our patient was identical to those reported in other patients with AIDS.

J Med Vet Mycol, 1993, 31(1), 55 - 64
Conditions affecting the adherence of Cryptococcus neoformans to rat glial and lung cells in vitro; Merkel GJ et al.; Conditions affecting the adherence of clinical isolates of Cryptococcus neoformans to rat glial and lung cell cultures were studied . Adherence to glial cells was a time-dependent process that was affected by the yeast culture age and growth temperature . The most adherent yeasts were those from 48 h cultures grown at 37 degrees C . Formalin-treating the yeasts did not affect adherence but formalin-treating the glial monolayers prevented yeast binding . Treating the yeasts with trypsin reduced adherence to glial monolayers, indicating that the yeast adhesin had a trypsin-labile protein component . Certain carbohydrates inhibited cryptococcal adherence to glial and lung cells in a time and concentration-dependent manner . Of the carbohydrates tested, N-acetyl-D-glucosamine, sucrose, lactose, sorbitol and myo-inositol were the most inhibitory, while mannose, galactose and xylose were the least inhibitory . The results collectively indicated that the mechanisms of adherence of C . neoformans to lung cells were similar to those of glial cells and that both involved a protein-containing adhesin on the cryptococcal surface that was expressed only after growth at 37 degrees C . Carbohydrate receptors also appeared to be involved with these interactions.

J Infect, 1993 Jan, 26(1), 83 - 6
Disseminated Mycobacterium flavescens in a probable case of chronic granulomatous disease; Allen DM et al.; We report the case of a diabetic Chinese male with no previous history of recurrent infections . His course was at first notable for relapsing Salmonella blockley infections, following which he developed repeated soft-tissue infections and Cryptococcus neoformans pneumonia . He was diagnosed as having chronic granulomatous disease and was treated with gamma interferon . During the latter stages of his illness he developed Mycobacterium flavescens infection in soft tissues, joints, bones and lung . This is the first report of disseminated M . flavescens infection.

Clin Infect Dis, 1993 Jan, 16(1), 54 - 8
Blastomycosis in transplant recipients: report of a case and review; Serody JS et al.; Fungi cause serious, often fatal infections in immunocompromised hosts . Recipients of solid organ and bone marrow transplants are predisposed to invasive fungal infections with Candida species, Aspergillus species, and Cryptococcus neoformans . In contrast, infections with Blastomyces dermatitidis have rarely been diagnosed in transplant recipients . We describe a patient who received an orthotopic heart transplant and developed recurrent disseminated blastomycosis . Other reported cases of blastomycosis in transplant recipients are summarized . Clinical presentation, treatment options, and morbidity associated with infections with B . dermatitidis in transplant patients are reviewed.

Can J Microbiol, 1993 Jan, 39(1), 129 - 33
Mannosyl transfer in Cryptococcus neoformans; White CW et al.; A particulate enzyme preparation from Cryptococcus neoformans transferred the mannosyl residue from GDP-mannose to an acceptor consisting of a commercial preparation of methyl 3-O-alpha-mannopyranosyl-alpha-mannopyranoside (containing 10% 2-O-alpha-mannopyranosyl-alpha-mannopyranoside) . The configuration of the new bond was alpha by its susceptibility to alpha-mannosidase; the amount of product was dependent on the concentration of enzyme, of GDP-mannose, and of acceptor . The optimal temperature and pH were 37 degrees C and 7.0, respectively . Manganous ion was required for activity and acetyl coenzyme A was stimulatory . Studies suggested that dolichyl phosphate intermediates were not involved in this mannose transfer . The fact that none of the several acapsular mutants tested were deficient in this mannosyltransferase suggested that this enzyme was not involved in synthesis of backbone mannan linkages in capsular polysaccharide . NMR analysis of the methylmannotriose product showed only alpha(1-->2) linkages between sugar moieties . This mannosyltransferase evidently extends alpha(1-->2) mannan by adding another alpha(1-->2)-linked mannosyl residue . Its activity is appropriate for a role in synthesis of "high mannose" oligosaccharide moieties of glycoproteins.

Thorax, 1993 Jan, 48(1), 75 - 8
Diagnosis of pulmonary cryptococcosis by ultrasound guided percutaneous aspiration; Lee LN et al.; BACKGROUND: Ultrasound is useful for locating thoracic lesions and guiding biopsy procedures . The use of sonographic appearances and ultrasound guided needle aspiration has led to the diagnosis of pulmonary cryptococcosis at this hospital . METHODS: Six hundred and eight patients who had ultrasound guided lung aspirations were reviewed retrospectively and nine with documented pulmonary cryptococcosis were collected . All patients had nodules or infiltrates on the chest radiograph . The needle aspirates obtained under ultrasound guidance were stained by Riu's or Papanicolaou's method or with India ink, and six were sent for culture . Five patients also underwent bronchoscopy and biopsy . RESULTS: The nine patients had 18 pulmonary lesions, of which 15 were nodules and three infiltrates . Fifteen lesions were detectable by ultrasound, which showed the nodules to be hypoechoic with eccentrically located air echoes . In eight of the nine cases cryptococci were detected after the lung aspirates had been stained with Riu's or Papanicolaou stain or with India ink . In five of the six aspirates sent for fungal culture Cryptococcus neoformans was isolated . The diagnostic yield was higher than that of bronchoscopy . None developed post-aspiration pneumothorax or any evidence of late dissemination . CONCLUSIONS: Because they tend to be subpleural pulmonary cryptococcal lesions seem to be identifiable by ultrasound . Ultrasound guided lung aspiration is an effective, rapid, and safe method for diagnosis.

Ann Pharmacother, 1993 Jan, 27(1), 53 - 60
Antifungal prophylaxis in immunocompromised hosts; Reents S et al.; OBJECTIVE: To review the literature on the efficacy and safety of antifungal agents for prophylaxis of fungal infections in populations of immunocompromised hosts (key words: hematology-oncology, surgical, solid organ transplant, HIV infection), and to develop guidelines and recommendations regarding safe and effective drug regimens for antifungal prophylaxis in this patient population . DATA EXTRACTION: Comprehensive review of clinical trials of antifungal prophylaxis published in the English literature, with an emphasis on controlled trials, and discussion of key clinical trials illustrating efficacy and safety of agents for antifungal prophylaxis in immunocompromised patients . RESULTS: Much of the clinical data evaluating the efficacy and safety of antifungal prophylaxis has been generated in cancer patients . The choice of antifungal agent for prophylaxis in this population remains controversial . However, azole compounds such as clotrimazole, ketoconazole and fluconazole appear to be more effective and better tolerated than nystatin suspension . Although ketoconazole has been shown to reduce fungal colonization in surgical patients, current data do not support the routine use of antifungal prophylaxis in this population . In renal transplant recipients, clotrimazole troches have been shown to be more effective than placebo or nystatin suspension . Selective bowel decontamination with nonabsorbable antibiotics and nystatin may be useful in reducing Candida colonization in liver transplant patients but no definitive recommendations may be made at this time regarding optimal antifungal prophylaxis in these patients . In patients with advanced HIV disease or history of prior fungal disease prophylaxis for oropharyngeal candidiasis is indicated, although the agent of choice remains controversial . Fluconazole is the drug of choice for prevention of relapse of cryptococcal meningitis in patients with AIDS . Finally, only limited data exist assessing the relationship between local colonization and systemic fungal infection . Adverse effects associated with antifungal prophylaxis, generally limited to nausea and vomiting and transient elevations in hepatic transaminases, occur with similar frequency among available oral or topical agents . However, the incidence of nausea and vomiting with resultant poor patient tolerance and compliance is usually higher with nystatin . CONCLUSIONS: Based on available data from controlled clinical trials, azole agents are currently the most effective and best-tolerated drugs for antifungal prophylaxis in immunocompromised hosts . Choice of one agent in this group over another may be dictated by cost . As new antifungal treatments are released onto the market, these drugs should be compared with existing agents in controlled clinical trials . Future studies should be designed to evaluate the relationship between local colonization and disseminated infection.

J Infect Dis, 1993 Jan, 167(1), 186 - 90
Regulation of cryptococcal capsular polysaccharide by iron; Vartivarian SE et al.; Iron is tightly controlled in mammalian tissues and regulates virulence factors in various pathogenic organisms . The influence of Fe availability upon production of cryptococcal capsular polysaccharide was studied . Polysaccharide, measured as cell-bound glucuronyl residues, increased more than threefold as available Fe in the culture medium was varied from repletion to tight sequestration and depletion in five incremental steps . Since physiologic CO2 concentration may serve as stimulus for cryptococcal polysaccharide synthesis, the combined effect of Fe availability and CO2 on encapsulation was studied . Addition of dissolved, loosely chelated Fe moderated the effect of CO2 . Tight chelation of dissolved Fe potentiated the CO2 effect . Tissue from infected mice showed heavily encapsulated organisms, consistent with results with physiologic CO2 concentration and Fe deprivation . In conclusion, cryptococcal polysaccharide synthesis is increased by limitation of ferric iron availability to the cell and by dissolved CO2, and the two effects are additive.

J Clin Microbiol, 1993 Jan, 31(1), 97 - 101
Evaluation of an enzyme immunoassay for detection of cryptococcal capsular polysaccharide antigen in serum and cerebrospinal fluid; Frank UK et al.; The Premier enzyme immunoassay (Meridian Diagnostics, Inc., Cincinnati, Ohio) was compared with a latex agglutination assay (CALAS; Meridian) for the ability to detect cryptococcal capsular polysaccharide antigen (CrAg) in serum and cerebrospinal fluid (CSF) . A total of 594 specimens (471 serum samples and 123 CSF samples) obtained from 430 patients, most of whom were at risk for or had AIDS, were tested in parallel by both systems . Both tests were independently evaluated for their ability to (i) detect CrAg when used as a screening test and (ii) quantitate the CrAg present when used as a titration assay . Chart review to assess clinical outcome after the time of specimen collection was conducted for all patients . When both assays were used as screening assays, 103 serum samples and 18 CSF samples were positive and 356 serum samples and 104 CSF specimens were negative by both assays (97.8% concordance) . Thirteen specimens (12 serum samples, 1 CSF sample) gave discrepant screening results . When the tests were used as semiquantitative assays for titer determinations, the CrAg titers determined by the enzyme immunoassay were generally higher than those obtained with the latex agglutination assay . In summary, results obtained with the enzyme immunoassay correlated well with those obtained with the latex agglutination test for screening for the presence of CrAg and for determining the titer of CrAg in serum or CSF.

Virchows Arch B Cell Pathol Incl Mol Pathol, 1993, 64(1), 57 - 66
Ultrastructural study of hepatic granulomas induced by Cryptococcus neoformans by quick-freezing and deep-etching method; Sakaguchi N; The ultrastructure of hepatic granulomas induced by Cryptococcus (C.) neoformans was studied by a quick-freezing and deep-etching (QF-DE) method . Viable yeast cells were inoculated intravenously into rats and the livers were prepared for QF-DE replicas . Two cytoskeletal components were identified in the cytoplasm of macrophages composing the cryptococcal granulomas . These were: intermediate filaments, mainly located in the perinuclear region, and actin filaments, which were extensively decorated with myosin subfragment 1 (S1) and formed networks in the peripheral portion of the cytoplasm . In addition, two types of macrophage pseudopodia were observed in the granulomas . These were cobble stone-like pseudopodia at the yeast-macrophages contract areas, and thin, long and occasionally interdigitating pseudopodia in which actin filaments were consistently observed . Dense networks of actin filaments were also seen in pseudopodia protruding into the tight structure of the capsule of C . neoformans . These results suggest a role for actin filaments as one of the main factors in the force generating system of the phagocytic process.

EXS, 1993, 67, 311 - 20
DNA- and PCR-fingerprinting in fungi; Meyer W et al.; DNA-fingerprinting has been successfully used to detect hypervariable, repetitive DNA sequences (minisatellites and microsatellites) in fungi . Combined with methods used to identify random amplified polymorphic DNA (RAPD), conventional DNA-fingerprinting hybridization probes can also be used as single primers to detect DNA polymorphisms among fungal species and strains . The oligonucleotides (CA)8, (CT)8, (CAC)5, (GTG)5, (GACA)4 and (GATA)4, as well as the phage M13 and its core sequence, have been used as specific probes in hybridization experiments and as primers for PCR analysis . Both methods have enabled the differentiation of all the fungal species and strains that were examined, including species of Penicillium, Trichoderma, Leptosphaeria, Saccharomyces, Candida and Cryptococcus . These methods have been used 1) to clarify the taxonomic relationships among relevant species of the Trichoderma aggregate, 2) to discriminate between aggressive and non-aggressive isolates of the rape seed phytopathogen, Leptosphaeria maculans, and 3) to identify strains of the pathogenic yeasts, Cryptococcus neoformans and Candida albicans . PCR-fingerprinting allowed serotypes of C . neoformans to be distinguished . The application of DNA- and PCR-fingerprinting to fungal DNA should aid in clarification of their taxonomy and improved diagnosis of mycotic disease.

J Clin Lab Anal, 1993, 7(3), 168 - 73
Dual organism infection in biopsy specimens from immunocompromised patients: two cases demonstrated by immunocytochemistry; Reed JA et al.; We report two cases in which immunocytochemistry demonstrated simultaneous infections within a single biopsy specimen obtained from each of two immunocompromised patients in whom multiple organism infection was not suspected . Using a rapid immunocytochemical technique, Pneumocystis carinii and Cryptococcus neoformans were demonstrated in a transbronchial lung biopsy from the first patient; Candida and cytomegalovirus were demonstrated in an endoscopic biopsy of the esophagus from the second patient . Routine hematoxylin and eosin as well as special stains failed to establish the presence of more than one infectious agent in either case . Mycology cultures ultimately confirmed the presence of Cryptococcus in the first case, but cultures were not performed in the second case due to the scant amount of tissue obtained from the biopsy . The results indicate that concurrent infection by more than one opportunistic organism in immunocompromised patients can easily remain unrecognized . The use of immunocytochemistry may thus provide an important adjunct to routine and special stains or specific cultures.

Radiol Med (Torino), 1993 Jan-Feb, 85(1-2), 40 - 8
{Opportunistic infections in AIDS . The pulmonary manifestations}; Scialpi M et al.; The initial and follow-up chest radiographs of 31 patients with the acquired immunodeficiency syndrome (AIDS) were reviewed to assess the spectrum and frequency of opportunistic pulmonary infections . In our series, the most common pulmonary infections seen on chest films were: Pneumocystis carinii pneumonia (PCP) (n = 17), PCP associated with Cytomegalovirus (CMV) (n = 2), PCP associated with Mycobacterium avium-intracellulare (MAI) (n = 1), Mycobacterium tuberculosis (n = 7), CMV (n = 2), MAI (n = 1) and Cryptococcus neoformans (n = 1) . Diffuse or focal interstitial infiltrate is the most common finding in PCP; bilateral focal or multilobar interstitial infiltrates are also frequently observed: they are usually caused by PCP or by PCP associated with CMV . Infiltrating cavitating lesions and multiple interstitial well-defined nodules < 10 mm diameter were seen only in Mycobacterium tuberculosis infections . Normal chest findings and/or pleural effusions were uncommon; no case exhibited pulmonary cysts on initial radiographs . In this retrospective study we emphasize the high incidence of Mycobacterium tuberculosis infections; other pulmonary infections are emerging in AIDS . The X-ray patterns of pulmonary infections in AIDS must be known for a prompt and accurate diagnosis and to plan the appropriate treatment.

Nephrol Dial Transplant, 1993, 8(2), 168 - 72
High mortality in systemic fungal infections following renal transplantation in third-world countries; Chugh KS et al.; Amongst 310 recipients of live related renal transplants, systemic fungal infections were observed in 19 patients (6.1%) . These included cryptococcosis in eight (42%), candidiasis in seven (37%), mucormycosis in two (11%), aspergillosis in one (5.5%), and a mixed cryptococcal and Aspergillus infection in one patient (5.5%) . Infections occurred within 12 months of transplantation in seven patients and after 13-37 months in the remaining patients . Prolonged fever not responding to antibiotics was the most common presentation . Central nervous system was involved in all patients with cryptococcosis, while Candida infection primarily involved the urinary tract . Both patients with mucormycosis exhibited signs and symptoms of florid rhinocerebral disease and a rapid downhill course . Pulmonary manifestations were the most prominent features of patients with aspergillosis . Parenteral amphotericin B with or without 5-fluorocytosine was started in all, but three patients could receive the therapy only for 1-3 weeks . Three patients with cryptococcosis developed amphotericin-related complications and were changed to oral fluconazole . Seven patients recovered and 12 (63%) died . None of the patients had cytomegalovirus infection preceding the onset of fungal disease . The high frequency of fungal infections amongst our allograft recipients could not be ascribed to over immunosuppression, since 16 patients (84%) were only on maintenance doses of immunosuppressive drugs and in 13 (68.4%) graft function was normal at the time of diagnosis . The high frequency of fungal infections in our patients was most probably related to the poor hygienic and sanitary conditions which continue to be prevalent in the tropical environment of third-world countries . Delays in the diagnosis and late institution of therapy result in a high mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

J Med Vet Mycol, 1993, 31(3), 189 - 99
Differential binding of acapsulate and encapsulated strains of Cryptococcus neoformans to human neutrophils; Richardson MD et al.; Investigations into mechanisms of binding of encapsulated and acapsulate strains of Cryptococcus neoformans by human neutrophils were performed, using a monolayer assay . The two strains bound to neutrophils by different mechanisms although both had an absolute requirement for opsonization with complement components in normal human serum for binding to occur . Neutrophil binding of encapsulated yeasts required conformational changes in actin yet did not appear to lead to phagocytosis of the organism . A maximum of 12 acapsulate cells bound per neutrophil compared with only four encapsulated yeasts . Cytochalasin D treatment reduced the maximum numbers able to bind per neutrophil by 50% . The encapsulated cryptococci appeared to compete with each other for binding to neutrophils whereas the acapsulate yeast cells bound to neutrophils in an approximately Poisson distribution, suggesting independent binding . Binding of acapsulate cryptococci did not require actin filaments and appeared to trigger phagocytosis . Thus, the capsule of C . neoformans appeared to inhibit binding and internalization by neutrophils.

Pathology, 1993 Jan, 25(1), 76 - 80
Comparative evaluation of cryptococcal latex tests; Warren RJ et al.; One hundred and seven specimens (24 CSF and 83 sera) from 90 patients were tested for the presence of Cryptococcus neoformans antigen using the Fairfield Hospital in-house latex agglutination technique and the IMMY and Meridian commercial latex agglutination kits . Forty one specimens (14 CSF and 27 sera) from 27 patients with culture-proven cryptococcosis were positive by both the Fairfield and IMMY latex tests . Thirty nine of these specimens were positive by the Meridian latex test . Two were negative . Sixty six specimens (10 CSF and 56 sera) from 63 patients not known to have cryptococcosis were negative by all 3 tests.

Mycoses, 1993 Jan-Feb, 36(1-2), 31 - 4
Evaluation of a commercial enzyme immunoassay for the detection of cryptococcal antigen; Sekhon AS et al.; A total of 143 cerebrospinal and serum samples, from proven and suspected cases of cryptococcosis, were concurrently examined using a recently introduced enzyme immunoassay (EIA Premier, Meridian Diagnostics, Inc., Cincinnati, OH, USA) and three latex agglutination (LA) procedures (Immunomycologics, Inc., Norman, OK, USA; IBL, Inc., Cranbury, NJ, USA and a non-commercial LA test) . Of these 143 specimens, 115 were negative for cryptococcal antigen (CrAg) with the EIA and LA tests . The remaining 28 specimens were evaluated by the LA tests, and all were positive for CrAg (with titres ranging from 1:2 to 1:8192) . Of these 28 LA-positive specimens, 26 were also tested by the EIA . This procedure detected CrAg in 23 specimens (88.5%), with antigen levels ranging from 1:4 to 1:266,857 . There were 3 LA-positive specimens (tires 1:4 to 1:32) which were negative by the EIA procedure (10.7%) . One LA-negative specimen demonstrated CrAg (titre 1:30) by the EIA procedure . The sensitivity of the EIA and LA tests was 85.2 and 100%, respectively . The specificity of the LA test was 100%, whereas that of the EIA was 97% . The agreement among laboratories for testing the specimens with the three LA tests was 100%.

Arch Med Res, 1993 Autumn, 24(3), 211 - 8
Opsonization and phagocytosis of Cryptococcus neoformans; Kozel TR; Cryptococcus neoformans is unique among the pathogenic fungi because the yeast is surrounded by an antiphagocytic polysaccharide capsule . Host resistance to cryptococcosis is dependent on natural defense mechanisms that cope with this essential fungal virulence factor . Recent studies in several laboratories indicate that, under appropriate circumstances, the antiphagocytic activity of the capsule can be overcome . A reversal of the antiphagocytic properties of the capsule requires (i) activation of the alternative complement pathway by encapsulated cryptococci, leading to deposition of the opsonic ligand iC3b at the capsular surface, (ii) presence of essential cytokines which up-regulate the efficiency of complement-dependent phagocytosis, and (iii) availability of phagocytic cells whose complement receptors are capable of appropriate up-regulation . Deficiencies in one or more components of the opsonization-phagocyte-cytokine triad may account, in part, for several features of the pathogenesis of cryptococcosis as well as the susceptibility of some immunocompromised patients to cryptococcosis . It may be possible to overcome some deficiencies by passive immunization with anticapsular IgG which takes advantage of phagocyte Fc receptors that are constitutively competent for phagocytosis or by therapeutic use of cytokines that up-regulate complement-dependent phagocytosis.

Microbiol Immunol, 1993, 37(10), 759 - 64
Characterization of a phenol oxidase from Cryptococcus neoformans var . neoformans; Ikeda R et al.; In Cryptococcus neoformans, enzymic oxidation of various catechols leads to melanin, a proposed virulence factor . A phenol oxidase enzyme of Cryptococcus neoformans var . neoformans produced at 25 C has been purified from an ultracentrifugal supernatant of an extract of broken cells . Hydrophobic interaction chromatography followed by anion-exchange column chromatography allowed purification of the phenol oxidase . The molecular weight of the enzyme estimated by gel filtration was about 80,000 and a dimeric species (Mw = 160,000) was suggested . The isoelectric point of the protein was approximately 4.1 . An NH2-terminal 31 amino acid sequence was determined using phenol oxidase electroblotted onto a PVDF membrane after nondenaturing gel electrophoresis . Upon searching the Peptide Institute (Osaka) data base, no proteins with high degrees of homology were found.

Rev Inst Med Trop Sao Paulo, 1993 Jan-Feb, 35(1), 81 - 7
{Treatment with fluconazole of severe fungal infections in immunocompromised patients}; Boulos M; Fluconazole therapy was evaluated prospectively in 108 patients with immunosupression and serious fungal infections . Patients were enrolled if they had a life-threatening fungal infection and conventional therapy had failed to eradicate infection, had caused serious toxic reactions, or was contraindicated . Patients were treated with 50 to over 400 mg/day initially . AIDS was underlying risk factor in 66.6% of the patients evaluated in the study and in 92.9% of 57 patients with cryptococcal infection . Satisfactory clinical response was observed in 43 patients with active cryptococcal infection and in 39 patients with active candidiasis, 90.7% and 92.3% respectively . Concerning mycologic response, 63.3% and 80.7% of 30 patients with cryptococcal infection and 26 patients with candidiasis respectively had final negative cultures . Eleven patients (10.2%) had adverse effects possibly due to fluconazole therapy . Fluconazole may be effective in the treatment of cryptococcal infection and candidiasis and can be an alternative to conventional antifungal therapy.

Rev Inst Med Trop Sao Paulo, 1993 Jan-Feb, 35(1), 77 - 9
{Cryptococcus neoformans var . neoformans isolated from soil}; Machado CC et al.; We inquiry, in the epidemiologic history of 42 patients with cryptococcosis, the contact with pigeon, trying to find the possible source of infection . Of these patients, the information compatible with ecologic niche of Cryptococcus neoformans was positive in 16 . Fifty nine samples were recovered from soil, associated with pigeon habitat . We found C . neoformans in four occasions, one in the capital and three in the interior of state . C . neoformans, serotype A, recovered from a central spine fluid coincides with the serotype of the fungus recovered downtown Porto Alegre, in a place suggested by the patient as possible source of infection, characterizing of a case of Cryptococcus neoformans . var . neoformans.

Rev Neurol (Paris), 1993, 149(5), 326 - 30
{Neurological form of cryptococcosis . Apropos of 2 atypical cases in non HIV-infected patients}; Donnet A et al.; Cryptococcal infection is the most common fungal infection of the central nervous system . More than 50% of the cases of cryptococcal infection are superimposed on an immunosuppressive or other general debilitating condition . Cerebral cryptococcosis usually presents as meningitis or meningoencephalitis, although cerebral granuloma has also been reported . Hydrocephalus is the most common neurosurgical complication of cerebral cryptococcosis . The majority of patients require only medical treatment with antifungal drugs . However, when complications ensue, surgical intervention is mandatory . We suggest that chronic meningitis be ruled out in all patients prior to the placement of shunts . In the two cases reported here treatment of cryptococcal meningitis was a combination of amphotericin B and flucytosine for six weeks . Fluconazole is a new alternative and at least as effective as amphotericin B.

Curr Top Med Mycol, 1993, 5, 1 - 26
Activation of the complement system by the capsule of Cryptococcus neoformans; Kozel TR; In vitro studies indicate that encapsulated cryptococci are among the most powerful particulate activators of the complement system reported to date . The capsule itself is the site at which activation occurs . Activation occurs solely via the alternative complement pathway . Initiation occurs at apparently random focal sites in the capsule that expand through alternative pathway amplification to fill the capsule with C3 fragments . The C3 fragments are rapidly converted to iC3b, suggesting that phagocyte receptors for iC3b will be important in phagocytosis of the yeast . There is abundant evidence that a similar form of activation occurs in vivo during a cryptococcal infection . Cryptococcemia in humans and experimental animals is accompanied by a depletion of serum complement levels . Studies with complement deficient guinea pigs and mice indicate that the complement system plays an essential role in resistance to cryptococcosis . It is likely that the complement system contributes to host resistance by opsonization of the yeast to facilitate attachment and ingestion by phagocytic cells as well as by releasing chemotactic fragments of the complement cascade which contribute to the inflammatory response . The absence or unavailability of a functional complement system in the central nervous system may account in part for the predilection of the yeast for the brain.

Ann Biol Clin (Paris), 1993, 51(2), 83 - 90
Immunological methods for the detection of structural components and metabolites of bacteria and fungi in blood; Gutierrez J et al.; This review compares the clinical usefulness of immunological methods for the detection of structural components and metabolites of bacteria and fungi . Bacterial antigens (especially those of Mycobacterium, Neisseria, Staphylococcus aureus, Yersinia enterocolitica, Escherichia coli, Salmonella, Chlamydia, and Brucella) are best detected by enzyme-linked immunosorbent assay . Methods involving antibodies are more expensive and are effective only when performed in series . The detection of antibodies that recognize S aureus teichoic acid merely confirms the presence of a metastatic complication . Tissue invasion by Candida albicans is not yet reliably detectable by the presence of a specific antigen . Simple, but not completely reliable methods are available such as the latex test for mannans detection and/or agglutination with liposomes for detecting 48-kDa cytoplasmic protein antigen and an assay for detecting enolase antigen . A latex agglutination test has also been developed for the mannans antigen of Aspergillus and for Cryptococcus neoformans capsular polysaccharide; the latter test is more cost effective . The sensitivity of both tests is improved by serial assays . A negative finding with hemagglutination-based antibody tests rules out C albicans infection, and titers of 1/640 or higher have been associated with disseminated infection by Aspergillus . Concentrations of C albicans blastopore antigen antibodies higher than 400 IU/ml can be seen in disseminated candidiasis . High concentrations of endotoxin are indicative of imminent septic shock . Some biological indicators (C reactive protein, angiotensin converting enzyme, fibronectin, elastase-alpha 1-antitrypsin complex, tumor necrosis factor and interleukin-6) have been used to rule out a bacterial cause of fever.(ABSTRACT TRUNCATED AT 250 WORDS)

Nat Toxins, 1993, 1(5), 294 - 5
Toxicity of cotton phytoalexins to zoopathogenic fungi; Mace ME et al.; The sesquiterpenoid phytoalexins desoxyhemigossypol, desoxymethoxyhemigossypol, and hemigossypolone formed in cotton (Gossypium hirsutum and G . barbadense) stem xylem infected with Verticillium dahliae were shown to be highly toxic to zoopathogenic fungi . This appears to be the first study of the toxicity of terpenoid phytoalexins to zoopathogenic fungi . The toxicities of the phytoalexins expressed as MIC (micrograms ml-1) values were 8 to 128 against four isolates of Candida albicans and one isolate of Cryptococcus neoformans . These highly toxic compounds or their derivatives may prove useful for the treatment of animal mycoses.

Ann Dermatol Venereol, 1993, 120(9), 612 - 5
{Septicemic cutaneous localization of cryptococcosis following renal transplantation in a female}; Dupond AS et al.; Cryptococcosis is a systemic disease caused by the yeast-like fungus Cryptococcus neoformans . Cutaneous manifestations, although rare, may precede other organ involvements . A case of cutaneous cryptococcosis is described herein . The skin lesions in our patient (a 47-year old female with renal transplant) consisted of acute cellulitis over her left and right thighs, revealing a septicemic infection . The patient received immunosuppressive drugs (prednisone, azathioprine) . Clinical, mycological and histopathological data are described in details . Amphotericin B and fluconazole were initially successful, but a relapse with Cryptococcus meningitis required the adjunction of itraconazole to treatment . This case report underlines the insufficient effectiveness of fluconazole and the success of itraconazole.

Acta Clin Belg, 1993, 48(6), 405 - 9
Fluconazole-resistant Cryptococcus neoformans var gattii in an AIDS patient; Peetermans W et al.; We describe a case of meningitis due to Cryptococcus neoformans var gattii in an AIDS patient . The reasons for the observed predominance of C . neoformans var neoformans infections in AIDS patients living in areas endemic for the gattii variety are not understood thus far . Treatment with fluconazole resulted in poor clinical and mycological response . In vitro sensitivity testing of the fungus revealed high minimal inhibitory concentrations, suggesting fluconazole resistance . Treatment with amphotericin B was successful.

Arch Med Res, 1993 Winter, 24(4), 403 - 12
Treatment of systemic mycoses in patients with AIDS; Graybill JR; Far and away the most common fungal infection associated with HIV infection is candidiasis . This tends to produce mucosal topical infections and local treatment may be enough to control them . Generally we prefer courses of 1-2 weeks rather than chronic suppression, for fear of eliciting overgrowth of resistant isolates . Fluconazole resistant Candida species may be an increasing problem over the next decade . For cryptococcoses the problem is both simpler and more complicated . Fluconazole is highly effective for chronic suppression, but not very effective for initial therapy . Here a short course of amphotericin B, just 2 weeks in length, is followed by chronic azole suppression . Fluconazole appears excellent, but itraconazole may also be effective . For histoplasmosis itraconazole appears to be the most advantageous drug, with excellent clinical response within 2 weeks . A role for fluconazole is unclear . Coccidioidomycosis is uncommon, but difficult . I cannot offer any suggestions on "ideal" therapy here . Other diseases, such as aspergillosis, are extremely uncommon but still are AIDS associated mycoses . It is my personal fear that as we go along identifying the AIDS virus and its complications, aspergillosis and zygomycosis may establish themselves as the future "black hats" for which we will need to pull something out of the "box" . What to pull is not very clear.

Arch Med Res, 1993 Winter, 24(4), 387 - 93
Itraconazole: pharmacokinetics and indications; Negroni R et al.; Itraconazole is a highly lipophilic triazolic compound, scarcely soluble in acidified polyethylene glycol, and soluble in hydroxypropyl-beta-cyclodextrin . It possesses an excellent digestive adsorption and its peak plasma level after oral administration of 100 mg is 0.16 microgram/ml at 3 or 4 h after drug intake . Half-life of itraconazole ranges between 17 to 21 h and 99.8% binds to plasmatic proteins, especially albumin . Metabolization is mainly done in the liver where inactive metabolites are formed with the exception of hydroxy-itraconazole, which exhibits a discrete antifungal activity . Stabilization of blood levels with repeated drug administration is reached at day 14, showing an increase both in plasma concentrations and in its half-life . Tissue levels of itraconazole are 3- to 20-fold higher than plasmatic concentrations, whereas only negligible concentrations are in CSF and urine . In the skin and particularly nails, itraconazole persists for a long time after discontinuation of therapy . Its mechanism of action is similar to other azolic compounds, inhibiting the alpha-14-demethylase of lanosterol which interferes with the synthesis of ergosterol . This drug behaves as a wide spectrum antifungal agent, acting against most pathogenic fungi with the exception of the Zygomycetes . Daily doses vary, according to indications, from 100 to 400 mg . The efficacy and results obtained in dermatomycosis, candidiasis, paracoccidioidomycosis, keratomycosis, sporotrichosis, chromoblastomycosis, coccidioidomycosis, blastomycosis, cryptococcosis, phaeohyphomycosis and maduromycotic mycetomas are detailed.

J Med Vet Mycol, 1993, 31(1), 65 - 75
Detection and differentiation of fungi in clinical specimens using polymerase chain reaction (PCR) amplification and restriction enzyme analysis; Hopfer RL et al.; We have developed a method for processing and detecting fungi in clinical specimens using the polymerase chain reaction (PCR) methodology . This PCR amplification of a segment of a ribosomal DNA gene results in a 310 bp product . The gene sequences used as amplimers have been highly conserved throughout the fungal kingdom and positive PCR results have been obtained for all genera and species of fungi tested (n = 42) . Neither human nor a variety of pathogenic bacteria (n = 24) gave an amplified product . This PCR method can detect as few as 15 cells of Candida albicans in clinical specimens following a simple processing procedure . The sensitivity of the PCR for detecting other fungi remains to be determined . Analysis of the 310 bp amplified product, following digestion with the restriction enzyme HaeIII, can be used to further characterize the identity of the fungus involved into the following five groups: (i) Candida species and closely related yeasts; (ii) Cryptococci and Trichosporon species; (iii) Aspergilli and clinically related septate molds; (iv) the Zygomycetes; and (v) the dimorphic fungi.

Rev Pneumol Clin, 1993, 49(5), 211 - 5
{Pulmonary diseases and retrovirus infections . A pathological study in 70 cases}; N'Dhatz M et al.; A necroscopic study, conducted in the Pathology Department of the Centre Hospitalier Universitaire (CHU) de Treichville in Abidjan, included 70 seropositive subjects who died in the Pneumophtisiology Department . We attempted to determine the different pulmonary affections occurring during infection with the human immunodeficiency virus (HIV) . This study demonstrated the predominant role of tuberculosis (44%) and bacterial pneumonia (30%) which remain the predominant aetiologies . Other opportunistic affections were rare including: Pneumocystises, Mycobacteriaceae, and Cytomegalovirus infection and the Kaposi sarcoma . The absence of pulmonary cryptococcosis and non-Hodgkin lymphoma were also noted . Necroscopic examinations do not necessarily provide evidence of the in vivo pathologies, the autopsy being able to identify only the causal diseases or those present at death.

Bull Soc Belge Ophtalmol, 1993, 250, 67 - 76
{Cryptococcal chorioretinitis and acquired immunodeficiency syndrome: apropos of a case}; Bibas P et al.; A patient with acquired immune deficiency and antecedents of pancreatitis presented with headaches, fever, dyspnea and bilateral decrease of vision . A diagnosis of disseminated cryptococcosis was made by lumbar puncture, alveolar washing and elevated cryptococcal antigen in blood, urine and stool . Bilateral chorioretinitis with ischaemic maculopathy was responsible of the low vision and attributed to cryptococcal infection after vitreous puncture and isolation of yeast from the vitreous . Systemic treatment with Amphotericin led to resolution of the chorioretinitis . A retinitis due to cytomegalovirus was associated short time before the patient died . Post-mortem anatomopathologic analysis revealed cryptococcus in high number in the choriocapillaris.

Adv Exp Med Biol, 1993, 335, 235 - 40
Epidemiology and infectious complications of human immunodeficiency virus antibody positive patients; Yangco BG et al.; From July 1, 1991 to March 31, 1992, 156 patients (pts) with positive antibody titers to the human immunodeficiency virus (HIV) were seen in our clinic . A retrospective review of the epidemiology and infectious complications of these patients is presented . There were 129 males and 27 females (4.8:1, ratio) . Only 10/156 (12.8%) were non-whites (13 blacks and 7 hispanics) . The majority, 126 (80.7%), were 25 to 44 years old . The most common risk factor was homosexuality or bisexuality 100 (64.1%), followed by heterosexual acquisition 25 (16%), intravenous drug abuse 23 (13.7%), unknown 6 (3.8%) and transfusion-related 3 (1.9%) . Sixty-five pts had no infections . In the remaining 91 pts, the infections noted were: candidiasis (54 pts); Pneumocystis carinii pneumonia (25 pts); Herpes simplex (13 pts); cytomegalovirus (CMV) retinitis (11 pts) and CMV esophagitis (1 pt), central nervous system toxoplasmosis (8); Herpes zoster (6 pts); cryptococcal meningitis (5 pts); Mycobacterium avium complex bacteremia (4 pts); Molluscum contagiosum, hepatitis-B, staphylococcal infection, perirectal abscess and oral hairy leukoplakia (2 pts each); syphilis, cryptosporidiosis, nocardiosis, histoplasmosis and laryngeal papillomatosis (1 pt each) . Infections were multiple in 57/91 (62%) pts and tend to occur more often when the helper cells are < 200 47/57 (82%) pts . Appropriate antimicrobials for prophylaxis and maintenance therapy appeared to decrease the occurrence or relapse of infections such as pneumocystosis, candidiasis, cryptococcosis, tuberculosis and toxoplasmosis.

Bull Soc Pathol Exot, 1993, 86(5 Pt 2), 484 - 8
{Human protothecosis and environment}; Huerre M et al.; Protothecosis are uncommon infections caused by Prototheca, considered to be achlorophylous algae . Nearly 80 human cases are reported in the literature since the first case described by Davies and Wakelin in 1964 in Sierra Leone (11) . The disease have been identified in Europe, Asia (Japan, Thailand, China), Oceania and in the United States with 40 cases, particularly in the Southeast . Clinically, three clinical manifestations can be observed: 1) cutaneous lesions: papules, plaques or eczematoid, papulo-nodular areas of the extremities, 2) olecranon bursitis which occurred in 25% of cases, 3) systemic protothecosis . An immunosuppressive factor local or general can be found in half of the cases and the first description of algal meningitis was reported in a patient with AIDS in association with Cryptococcus neoformans . Because the disease is clinically not suspected, the diagnosis is often provided by histology showing a dermic granuloma with endospores . The characteristic feature of protothecosis in tissues is the presence of specific mature sporangia of Prototheca wickerhamii with the pattern of morula . The organism was PAS, Grocott and mucicarmin positive . The ecology was studied by Clark (7), Pidoux (23), Pore (25) and Sudman (27) . Prototheca are ubiquitous inhabitants of sewages and are found in slime flux and animal wastes contaminating different aquatic systems . The transmission generally occurred by traumatic inoculation . Prototheca are also found in the digestive system of man and animals without never invasion of the epithelium and mucosae in experimental models . The pathogenicity and virulence are moderate and they are considered as rare opportunistic agents.

Mod Pathol, 1993 Jan, 6(1), 80 - 4
Combined histochemical stains in the differential diagnosis of Cryptococcus neoformans; Lazcano O et al.; Three combinations of histochemical stains were used to study 69 routinely processed tissues containing various "yeast-like" fungal organisms (Cryptococcus neoformans, Blastomyces dermatitidis, Coccidioides immitis, Histoplasma capsulatum, Paracoccidioides brasiliensis, and Candida albicans) . Fontana-Masson stain combined either with mucicarmine or Alcian blue produced distinctive staining of C . neoformans (Fontana-Masson-positive wall and mucin-positive capsule) that was not identified in other fungi . The Alcian blue stain combined with periodic acid-Schiff reaction also was useful for fungal classification, because the Alcian blue component reacted with only C . neoformans (capsule) and B . dermatitidis (wall) and the periodic acid-Schiff reaction reacted with the cell wall and body of each fungus . We concluded that the combined histochemical stains used in conjunction with morphologic study of hematoxylin and eosin- and Gomori methenamine silver-stained sections are helpful in the differential diagnosis of yeast-like fungal organisms.

J Clin Microbiol, 1992 Dec, 30(12), 3138 - 45
Collaborative comparison of broth macrodilution and microdilution antifungal susceptibility tests; Espinel-Ingroff A et al.; A collaborative comparison of macro- and microdilution antifungal susceptibility tests was performed in five laboratories . MICs of amphotericin B, fluconazole, flucytosine, and ketoconazole were determined in all five centers against 95 coded isolates of Candida spp., Cryptococcus neoformans, and Torulopsis glabrata . A standard protocol with the following National Committee for Clinical Laboratory Standards Subcommittee on Antifungal Susceptibility Testing recommendations was used: an inoculum standardized by spectrophotometer, buffered (RPMI 1640) medium (pH 7.0), incubation at 35 degrees C, and an additive drug dilution procedure . Two inoculum sizes were tested (1 x 10(4) to 5 x 10(3) to 2.5 x 10(3) CFU/ml) and three scoring criteria were evaluated for MIC endpoint determinations, which were scored as 0 (optically clear), < or = 1 (slightly hazy turbidity), and < or = 2 (prominent decrease in turbidity compared with that of the growth control) . Overall intra- and interlaboratory reproducibility was optimal with the low-density inoculum, the second-day readings, and MICs scored as either 1 or 2 . The microdilution MICs demonstrated interlaboratory agreement with most of the four drugs higher than or similar to that of the macrodilution MICs . In general, there was good interlaboratory agreement with amphotericin B, fluconazole, and flucytosine; ketoconazole gave more variable results.

Antimicrob Agents Chemother, 1992 Dec, 36(12), 2722 - 8
Activity of MS-8209, a nonester amphotericin B derivative, in treatment of experimental systemic mycoses; Saint-Julien L et al.; The in vitro and in vivo toxicities and activities of MS-8209, a new hydrosoluble amphotericin B (deoxycholate-amphotericin B {D-AmB}; Fungizone) derivative, were studied . In vitro, MS-8209 was less toxic than AmB against renal tubular cells in primary culture and less active against Candida albicans and Cryptococcus neoformans . However, at 10-fold the AmB concentration, MS-8209 in vitro antifungal activity paralleled that of AmB . Fifty-percent lethal doses of MS-8209 and D-AmB in OF1 noninfected mice were 26 and 2.3 mg/kg, respectively . Therapeutic efficacy of MS-8209 was assessed in murine candidiasis, cryptococcosis, and aspergillosis . In each model of infection, we determined the maximum tolerated dosages of MS-8209 and D-AmB, i.e., the dosage inducing less than 15% mortality due to toxicity; the efficacies of MS-8209 and D-AmB at their respective maximum tolerated dosages were compared . In candidiasis, MS-8209 (15 mg/kg) significantly increased the survival time compared with D-AmB (0.5 mg/kg) . Both compounds were equally effective at reducing CFU counts in the kidney . MS-8209 was the most effective agent for increasing the survival time in cryptococcal meningoencephalitis and for reducing CFU counts in spleen, brain, and lung during both cryptococcal pneumonia and meningoencephalitis . In aspergillosis, MS-8209 and D-AmB similarly prolonged the survival of treated mice compared with controls . These results show that when MS-8209 and D-AmB were used at the maximum tolerated dosage, MS-8209 was as effective as or more effective than D-AmB for the treatment of systemic mycoses . These findings warrant further experiments to study the pharmacokinetic properties and toxicity of MS-8209 under conditions of chronic administration.

Antimicrob Agents Chemother, 1992 Dec, 36(12), 2656 - 60
Efficacy and safety of amphotericin B colloidal dispersion compared with those of amphotericin B deoxycholate suspension for treatment of disseminated murine cryptococcosis; Hostetler JS et al.; The efficacy and safety of amphotericin B colloidal dispersion (ABCD) were compared with those of amphotericin B deoxycholate suspension (ABDS) (Fungizone) in a murine model of disseminated cryptococcosis . Mice were treated intravenously with either ABDS at 0.2, 0.8, or 3.2 mg/kg of body weight per dose or ABCD at 0.8, 3.2, 6.4, 12.8, or 19.2 mg/kg dose three times per week for 2 weeks . Excluding mice treated with ABDS at 3.2 mg/kg, which was acutely lethal in 100% of mice, and ABCD at 19.2 mg/kg, which also resulted in two early deaths, the survival of ABCD- and ABDS-treated groups was prolonged over survival of controls (P < or = 0.05) . Survival of ABCD (3.2 mg/kg)-treated mice was improved over that of ABDS (0.2 mg/kg)-treated mice (P < 0.05); however, comparisons of mice given all other dosages of ABCD with mice given sublethal dosages of ABDS did not demonstrate differences in survival . Comparative fungal burdens in organs showed a decrease in liver (P < 0.05) and spleen (P < 0.05) burdens for ABCD with the 19.2-mg/kg therapy versus those with ABDS with the 0.8-mg/kg therapy and liver burdens for ABCD with the 12.8-mg/kg therapy versus ABDS with the 0.8-mg/kg therapy (P < 0.05) . There was no difference in organ burdens between therapy with ABCD at 0.8 mg/kg and ABDS at 0.8 mg/kg . These data show that the efficacy of ABCD is equal to that of ABDS on a milligram-per-kilogram basis for murine disseminated cryptococcosis . Because of its decreased toxicity, greater efficacy with ABCD could be achieved through doses fourfold higher than the 100% lethal dose for ABDS . Thus, ABCD shows promise as an effective but less toxic alternative to ABDS for the treatment of disseminated cryptococcosis.

Am Rev Respir Dis, 1992 Dec, 146(6), 1434 - 8
HIV-1 envelope protein (gp120) inhibits the activity of human bronchoalveolar macrophages against Cryptococcus neoformans; Wagner RP et al.; Cryptococcus neoformans infections are a major cause of morbidity and mortality for HIV-infected persons . Containment of the initial respiratory inoculation to the lung appears defective in patients with AIDS despite the low burden of HIV in bronchoalveolar macrophages . We have studied the fungistatic activity of human bronchoalveolar macrophages (BAM) cultured with an encapsulated strain of C . neoformans in the presence of pooled human serum . We observed 51.6% fungistasis after 24 h of culture . Fungistasis was diminished if the pooled human serum was heat-inactivated but was not affected by anticryptococcal capsular IgG . HIV envelope protein (gp120) has been shown to interfere with lymphocyte activation in vitro . We studied the effects of gp120 on BAM function and found that fungistatic activity was inhibited 25% (p < 0.001) . Although binding of yeasts was not affected, gp120 inhibited the internalization of bound yeasts by 46% (p = 0.025) . These experiments indicate that gp120 decreases the internalization and fungistasis of C . neoformans by human BAM, and they suggest a mechanism to explain how a small number of HIV-1-infected cells in the lung could impair the containment of C . neoformans.

J Clin Microbiol, 1992 Dec, 30(12), 3239 - 42
Value of extended agitation and subculture of BACTEC NR 660 aerobic resin blood culture bottles for clinical yeast isolates; Prevost-Smith E et al.; From 10,351 blood cultures, we prospectively studied 1,000 BACTEC NR 660 aerobic resin blood culture bottles (26+ and Peds Plus) for patients suspected of having yeast septicemia to determine whether extended agitation and subculturing would increase the recovery of yeasts . Aerobic bottles were agitated continuously for 144 h . On day 7, 1,000 culture-negative aerobic bottles which had fungal blood culture requests were agitated for an additional 14 days . During this time they were subcultured twice and read twice by BACTEC NR 660 . ON days 1 to 7, 81 bottles were cultured positive for yeasts from 36 patients, which included 44 isolates of Candida albicans, averaging 1.4 days to detection, and 12 isolates of Cryptococcus neoformans, averaging 3.8 days to detection . The average detection time for all yeasts was 2.2 days . On days 7 to 21, no yeasts were detected by BACTEC or recovered from the subcultures . We conclude that when continuously agitated for at least 5 full days (120 h), the BACTEC NR 660 aerobic resin bottles reliably isolate yeasts, and it is unnecessary to subculture or hold these bottles beyond 5 days . It also eliminates the need for an additional blood culture system for yeast detection, thus saving (i) confusion in the collection process, (ii) patients' blood and money, and (iii) laboratory technologists' time.

Gene, 1992 Dec 1, 122(1), 213 - 7
Cloning the Cryptococcus neoformans TRP1 gene by complementation in Saccharomyces cerevisiae; Perfect JR et al.; We have cloned the phosphoribosyl anthranilate isomerase (PRAI)-encoding gene (TRP1) of Cryptococcus neoformans by genetic complementation in Saccharomyces cerevisiae . Sequence analysis of this gene revealed it to be 939 bp in length, and without known promoter or termination sequences . Unlike some of the filamentous fungi, where PRAI enzymatic activity is controlled by a trifunctional gene product, the C . neoformans PRAI appears to be unifunctional . PRAI of C . neoformans exhibits 39% amino acid (aa) sequence identity compared to the S . cerevisiae counterpart . The TRP1 gene of C . neoformans maps to different size chromosomes in strains with different serotypes . The cloning of this gene for vector constructions, and the demonstration that S . cerevisiae can be used as a surrogate for C . neoformans gene expression, should help with the molecular studies of this significant fungal pathogen in our increasing immunocompromised population.

Plast Reconstr Surg, 1992 Dec, 90(6), 1065 - 7
Primary cutaneous cryptococcosis as the presenting manifestation of AIDS; Song IC et al.; Presented is a case of primary cutaneous cryptococcosis, presenting as a papular facial lesion with subsequent ulceration, as the initial manifestation of AIDS . This unusual condition must be considered in the workup of unexplained or therapeutically unresponsive skin lesions . If it is diagnosed in an ostensibly "healthy" individual, evaluation for evidence of immunosuppression, and its underlying cause, must be undertaken.

J Pediatr, 1992 Dec, 121(6), 873 - 9
Cryptococcal osteomyelitis and cellular immunodeficiency associated with interleukin-2 deficiency; Sorensen RU et al.; We describe an unusual example of cellular immunodeficiency associated with interleukin-2 deficiency in an otherwise healthy 15-year-old boy who had isolated cryptococcal osteomyelitis of the scapula at 10 years of age . His previous medical history was remarkable only for prolonged, severe varicella infection at 6 years of age . He had persistent moderate lymphopenia, anergy, and absent lymphocyte blastogenic responses to mitogens, antigens, or monoclonal T cell antibodies . Subnormal blastogenic responses were seen after exposure to high concentrations of phorbol esters . Immunoglobulin levels and specific antibodies were normal . The patient has been in good health since treatment of his osteomyelitis . However, his lymphocyte blastogenic responses to mitogens have remained absent during 4 years of observation; investigation of the cause revealed a specific interleukin-2 deficiency resulting from defective generation of interleukin-2 messenger ribonucleic acid . Secretion of interleukin-1 by monocytes was normal, suggesting that the abnormal blastogenic response and interleukin-2 production were due to a problem intrinsic to T lymphocytes . The generation of messenger ribonucleic acid for interleukin-4 was not affected . Interferon-gamma was produced at subnormal levels . The addition of recombinant interleukin-2 restored lymphocyte blastogenic responses and increased the expression of interleukin-2 receptors . The clinical findings and immunologic abnormalities present in this patient differ from other primary and secondary immunodeficiencies associated with interleukin-2 deficiency . Thus our observations in this patient extend the spectrum of immunodeficiencies associated with abnormalities in the production of this important cytokine.

Arq Neuropsiquiatr, 1992 Dec, 50(4), 491 - 6
CSF in 85 patients with AIDS and CNS cryptococcosis; Livramento JA et al.; In an eight years time period (July 1984-June 1992) CSF samples of 40718 patients were studied, and 610 were from patients with AIDS clinically diagnosed and immunologically confirmed through HIV antibodies detection . Among opportunistic infections detected in them 85 were CNS cryptococcosis . For the purpose of this study the CSF of these 85 patients are the AIDS group of CNS cryptococcosis . For comparison, CSF data from 50 patients with CNS cryptococcosis but without AIDS were taken (non-AIDS group); in this group, 22 patients were immunosuppressed after renal transplant . In AIDS group, the more frequent CSF findings were: yeast presence at direct exam (Fuchs-Rosenthal cell counting chamber), growing of the yeast in cultures, and gamma globulins increase . In non-AIDS group were more frequent: hypercytosis, neutrophil cells presence, and total protein increase . Differences between the two groups are discussed taking into account CNS/CSF immune changes induced by HIV infection . It is concluded that in CNS cryptococcosis of patients with AIDS the CSF evidenced more extensive signs of the fungal opportunistic infection than signs of inflammatory response to the infection . The latter were more prominent among patients of the non-AIDS group of CNS cryptococcosis.

Intern Med, 1992 Dec, 31(12), 1401 - 5
Disseminated cryptococcosis presenting with adrenal insufficiency and meningitis: resistant to prolonged antifungal therapy but responding to bilateral adrenalectomy; Takeshita A et al.; A case of disseminated cryptococcosis with features of primary adrenal insufficiency and meningitis in an immunocompetent host is presented . Despite antifungal chemotherapy, neither meningitis nor bilateral adrenal gland enlargement was improved . Aspiration biopsy of the adrenal gland revealed necrotic tissue with numerous fungi, suggesting that the adrenal glands were the focus of the persistent fungemia . Removal of bilateral adrenal glands led to improvement by making the patient more sensitive to antifungal chemotherapy.

Enferm Infecc Microbiol Clin, 1992 Dec, 10(10), 607 - 10
{Pulmonary cryptococcosis in AIDS}; Martos A et al.; We present here three AIDS patients with disseminated cryptococcal infection and lung involvement . Two patients presented with respiratory symptoms and in the third one, pulmonary disease was only a radiologic finding . Chest X-ray films showed an interstitial pattern in two cases and pulmonary cavitation in one case . One patient has also simultaneous infection by P . carinii . Diagnosis was established by culture from bronchoalveolar lavage in all cases and also by non-induced sputum exam in two cases . All patients were treated with amphotericin B, with good clinical outcome, and without relapses under maintenance therapy with fluconazole . Cryptococcosis must be included in differential diagnosis of AIDS patients with diffuse interstitial lung infiltrates . The presence of C . neoformans in respiratory samples does not rule out the existence of other opportunistic infections, and therefore bronchoalveolar lavage is advisable.

Ann Soc Belg Med Trop, 1992 Dec, 72(4), 283 - 8
Evaluation of the cryptococcal antigen test as a diagnostic tool of AIDS-associated cryptococcosis in Rwanda; Swinne D et al.; To evaluate the latex test, two different retrospective studies were undertaken . A positive culture for Cr . neoformans was used as the golden standard of active cryptococcal infection . 439 sera selected at random sent to the NSP laboratory for screening of HIV antibody were tested as well as--71 CSF from patients with meningeal symptoms sent to the laboratory of the Centre Hospitalier de Kigali . In total, two discrepancies were found: two CSF samples from ancient cases of cryptococcosis under treatment were positive with the latex test and negative by culture . If it stands to reason that the antigen test cannot differentiate between active and inactive cryptococcal diseases, the persistence of small amounts of soluble antigens in a CSF implies that the patient must remain under surveillance, a relapse being very frequent in AIDS patients . As a conclusion, the latex test is a fast, easy to perform and quite reliable test for the diagnosis of cryptococcosis.

J Antimicrob Chemother, 1992 Dec, 30(6), 781 - 90
A non-azole inhibitor of lanosterol 14 alpha-methyl demethylase in Candida albicans; Capobianco JO et al.; 6-Hydroxy-N-methyl-N-(2-{4-phenylphenyl} ethyl)-1,2,3,4-tetrahydro-1- napthalene methanamine (A60586), a new non-azole inhibitor of ergosterol biosynthesis in Candida albicans ATCC62376 has been identified . In whole cells A60586 produced a dose related reduction of {14C}acetate incorporation into ergosterol and a concurrent increase in the radiolabelling of 4,4-dimethylated sterols . Similar observations were made with {14C}mevalonic acid lactone labelled cell free extracts . The IC50s for inhibition of ergosterol in the whole cell and cell free systems were 22 microM (10 mg/L) and 7.8 microM (3.5 mg/L), respectively . Analysis by gas chromatography of sterols from cells previously incubated at 37 degrees C for 24 h with A60586 (200 mg/L) confirmed the presence of lanosterol and 14 alpha-methyl fecosterol . These data indicate that A60586, inhibits the demethylation of the C-14 methyl group of lanosterol . The MIC of A60586 for several candida strains ranged from 12.5 to 50 mg/L, and against Cryptococcus albidus and Aspergillus niger ranged from 50 to 100 mg/L . The best in-vitro activity of A60586 was against Torulopsis glabrata (MIC range = 3.12 to 50 mg/L) . The membrane permeabilizing effect of this compound (50% leakage of {14C}aminoisobutyric acid at 70 mg/L A60586) may have contributed to its in-vitro antifungal activity.

J Am Vet Med Assoc, 1992 Nov 15, 201(10), 1591 - 2
Cryptococcal pneumonia and abortion in an equine fetus; Blanchard PC et al.; Cryptococcus neoformans was the causative agent of pneumonia in a 9-month-old equine fetus aborted by a healthy American Paint mare . Endometritis was diagnosed on biopsy, and vaginal specimens obtained for culture were Cryptococcus-positive 1 month following abortion but not 5 months after abortion . Infection resolved without treatment between 1 and 5 months after abortion, and the mare was bred the following year and delivered a live premature foal without evidence of Cryptococcus infection.

J Clin Microbiol, 1992 Nov, 30(11), 2881 - 6
Susceptibility testing of Cryptococcus neoformans: a microdilution technique; Ghannoum MA et al.; We studied a series of test conditions in a microtiter system to define the optimal method for determining the susceptibility of Cryptococcus neoformans to antifungal agents . Twenty-one isolates of C . neoformans were grown for 24 or 48 h in four chemically defined media: yeast nitrogen base (BYNB 7); RPMI 1640; synthetic amino acid medium--fungal (SAAMF), buffered at pH 7.0 to select the medium that best supported growth of this fastidious yeast; and yeast nitrogen base, pH 5.4 (YNB 5.4) . Maximum growth of C . neoformans, at 35 degrees C, was obtained in YNB 5.4, with the next highest growth levels in BYNB 7, SAAMF, and RPMI . Growth at 24 h was uniformly poor in all media and lacked reproducibility . In contrast, incubation for 48 h gave adequate growth with low standard deviations, and 48 h was selected as the optimal incubation period for this study . Comparison of the relationship between growth kinetics and initial inoculum size for eight cryptococcal isolates showed that 10(4) cells per ml yielded optimal growth in BYNB 7 and YNB 5.4, whereas 10(5) cells per ml was optimal in RPMI and SAAMF . Furthermore, variation of inocula from 10(3) to 10(5) cells per ml showed small but significant inoculum effects in determining MICs of fluconazole, amphotericin B, and flucytosine for C . neoformans . Therefore, 10(4) cells per ml was chosen as the optimal inoculum for susceptibility testing in this study . Mean MICs of fluconazole, amphotericin B, and flucytosine for 21 crytococcal isolates in RPMI and BYNB 7 were low (for example, fluconazole had mean MICs of 1.2 and 1.3 micrograms/ml in RPMI and BYNB 7, respectively) and differed significantly from medium to medium . In contrast, the MICs obtained in SAAMF were significantly higher (e.g., fluconazole had a mean MIC of 2.2 micrograms/ml) . Variance in MICs was large with fluconazole and flucytosine but small with amphotericin B, irrespective of the medium used . A microtiter system employing BYNB 7 as the medium, 48 h as the incubation period, and 10(4) cells per ml as the final inoculum is a simple, accurate, and reproducible method for the testing of C . neoformans susceptibility to fluconazole, amphotericin B, and flucytosine.

Enferm Infecc Microbiol Clin, 1992 Nov, 10(9), 543 - 6
{Fungemia caused by Rhodotorula mucilaginosa in relation to total parenteral nutrition}; Jimenez-Mejias ME et al.; BACKGROUND: Fungal infections are nowadays more common in clinical practice . The most frequently isolated fungi are Candida and Cryptococcus . Infection due to Rhodotorula mucilaginosa is very uncommon . We describe here our experience with R . mucilaginosa fungemia, with emphasis on total parenteral nutrition related episodes . METHOD: A retrospective review identified 3 patients with R . mucilaginosa, and predisposing conditions, clinical features, treatment used and outcome were analyzed . The case definition includes the repeated isolation of R . mucilaginosa in several blood-cultures and/or the isolation of R . mucilaginosa in one single blood culture together with its isolation in any other site . RESULTS: Three patients were identified . In all of them there are some defects in immune response (skin anergy in two, immunosuppressive therapy in the remaining patient), had an iv line placed, under antibiotic therapy and total parenteral nutrition . All factors could have been related to the development of R . mucilaginosa infection . CONCLUSION: Although its pathogenic role is controversial, in two or our patients R . mucilaginosa infections correlates well with clinical signs and symptoms of invasive infections (fever, hemodynamic changes) . The treatment is still not clear.

Nihon Kyobu Shikkan Gakkai Zasshi, 1992 Nov, 30(11), 1911 - 6
{A comparison of community-acquired lung infection and nosocomial infection--review of autopsy cases in Hisayama town}; Miyazaki H et al.; All people in Hisayama town who died either at home or in hospital are autopsied in Kyushu University Hospital . We examined the incidence and the pathogen of community-acquired lung infection and nosocomial infection from the records of 463 autopsy cases from 1977 to 1988 . Of these cases, 243 died at home . Among them, pulmonary infections were present in 122 cases (50.2%), and pulmonary infection was the cause of death in 87 cases (35.8%) . Of 220 cases that died in hospital, pulmonary infections were present in 133 cases (60.5%) and were the cause of death in 83 cases (37.7%) . In the cases that died at home, the incidence of pulmonary infections during the first 6-year period of the study was almost the same as that during the last 6 years . In the case that died in hospital, the incidence of pulmonary infections during the last 6-year period was higher than that during the first 6-year period . Regarding the pathogenic organisms of the fungal infections, only Candida was detected in case that died at home, while Candida, Aspergillus and Cryptococcus were detected in the case that died in hospital.

J Nat Prod, 1992 Nov, 55(11), 1664 - 8
Antifungal activity of meridine, a natural product from the marine sponge Corticium sp; McCarthy PJ et al.; Meridine {1}, a polycyclic alkaloid derived from the marine sponge Corticium sp., was found to inhibit the growth of Candida albicans and Cryptococcus neoformans . Activity was also observed against Trichophyton mentagrophytes and Epidermophyton floccosum . Studies of the mechanism of action of this agent have shown an inhibition of nucleic acid biosynthesis.

Clin Infect Dis, 1992 Nov, 15 Suppl 1, S274 - 81
Evaluation of new antifungal drugs for the treatment of systemic fungal infections . Infectious Diseases Society of America and the Food and Drug Administration; Medoff G et al.; These guidelines are applicable to all fungal pathogens that produce systemic infections in humans . Specific examples are provided whenever they might clarify special issues . Systemic fungal infections usually are divided into two broad categories: endemic systemic fungal diseases, which occur classically in healthy hosts, and opportunistic fungal diseases, which occur almost exclusively in patients with impaired host defenses . Both the increasing frequency of disseminated histoplasmosis and coccidioidomycosis in patients with AIDS and the occurrence of candidemia due to vascular-line infections have begun to blur this distinction . The fungi included in these guidelines are Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatitidis, Candida species, Cryptococcus neoformans, Aspergillus species, and Sporothrix schenckii . Diagnosis of infections caused by these fungi should be based on culture of infected body fluids or tissues whenever possible . Cryptococcal and coccidioidal meningitis are exceptions . Amphotericin B remains the standard comparative agent for most new agents . Further studies of the efficacy of new oral agents used alone or after a hospital course of amphotericin B are needed . The agents currently available are usually inadequate for eradication of fungal infections in patients with AIDS, who may need prolonged treatment . Final assessment for these patients may need to be classified as clinical cure with presumed microbiologic persistence.

Clin Infect Dis, 1992 Nov, 15 Suppl 1, S189 - 94
Evaluation of new anti-infective drugs for the treatment of cryptococcal meningitis . Infectious Diseases Society of America and the Food and Drug Administration; Lentnek A et al.; Cryptococcus neoformans may infect persons with intact or compromised host defenses . Clinical manifestations generally correlate directly with the degree of immunosuppression . Treatment is prescribed on the basis of the severity of disease and the degree of immunosuppression . Cryptococcal meningitis is the most common clinical form of cryptococcal infection and the most amenable to study in clinical trials . The current standard of care for cryptococcal meningitis is therapy with amphotericin B . Despite clinical improvement and microbiological suppression of the organism at the completion of therapy, the microbiological outcome will be identified as presumptive persistence if treatment is continued . Patients should be observed for 1 year after completion of therapy before a final assessment is made.

FEMS Microbiol Lett, 1992 Nov 1, 77(1-3), 187 - 90
Dimorphism in Itersonilia perplexans: yeast and hyphal phases differ in their sensitivity to mycocins produced by tremellaceous yeasts; Golubev W et al.; The monokaryotic yeast phase of the heterobasidiomycete Itersonilia perplexans, unlike the hyphal phase, was found to be sensitive to mycocins produced by killer strains of Cryptococcus humicola, Cr . laurentii, Cystofilobasidium bisporidii and Rhodotorula fujisanense . Both the yeast and hyphal phases wer resistant to mycocins of Cr . podzolicus, Filobasidium capsuligenum, Rhodotorula glutinis, Rh . mucilaginosa, Rh . pallida, Sporidiobolus johnsonii, Sb . pararoseus and Sporobolomyces alborubescens . The different sensitivity patterns of yeast and hyphal phases are probably caused by biochemical differences in the cell walls.

J Clin Microbiol, 1992 Nov, 30(11), 2960 - 7
DNA probe for strain typing of Cryptococcus neoformans; Varma A et al.; A 7-kb linear plasmid, harbored by a URA5 transformant, hybridized to all the chromosomes of Cryptococcus neoformans separated by contour-clamped homogeneous electric field electrophoresis . Its linear maintenance was determined to have been facilitated by the presence of telomere-like sequences at its free ends . Hybridization of this plasmid to AccI-digested genomic DNAs of 26 C . neoformans strains generated 21 unique DNA fingerprints . The DNA fingerprints of isolates within the same serotype were more similar to one another than to those from different serotypes . An acapsular clinical isolate, strain 602, widely used in immunological studies and previously thought to be in serotype D, showed DNA fingerprints typical of serotype A isolates . Isogenic strains of C . neoformans exhibited DNA fingerprints that were identical to one another . The DNA fingerprints were stable and reproducible in spite of repeated transfers in the laboratory on either complex (1% yeast extract, 2% Bacto Peptone, 2% glucose) or minimal (yeast nitrogen base) medium . The DNA fingerprints of isolates recovered from primary blood and cerebrospinal fluid cultures of patients for whom AIDS had been diagnosed showed that the original infection in each of these patients contained a homogeneous population of C . neoformans . The DNA fingerprints of isolates recovered from different tissues of infected mice and from patients undergoing different drug therapy regimens were also found to be very stable.

Infect Immun, 1992 Nov, 60(11), 4534 - 41
Protective murine monoclonal antibodies to Cryptococcus neoformans; Mukherjee J et al.; Several murine monoclonal antibodies (MAbs) specific for the capsular glucuronoxylomannan of Cryptococcus neoformans were studied for their capacity to confer protection when passively administered to lethally infected mice . The MAb group studied recognized at least three distinct epitopes and included immunoglobulin M (IgM), IgG3, IgG1, and IgA isotypes . The protection model used A/J and BALB/c mice infected intraperitoneally with 10(8) cryptococci . The MAbs were administered either immediately preceding or, in one experiment, 24 to 48 h prior to infection . Protective efficacy was assessed by the ability of passively administered MAbs to prolong the survival of lethally infected mice . Three IgM MAbs, each of which recognized a distinct epitope, were able to prolong survival of lethally infected mice to different extents . A set of IgM, IgG3, IgG1 and IgA MAbs which utilize the same immunoglobulin gene elements and were derived from the same B-cell clone exhibited significant class differences in protective efficacy with IgA, IgG1 > IgM > IgG3 . The results confirm that protective MAbs against C . neoformans capsular polysaccharide exist and strongly suggest that both epitope specificity and isotype are important determinants of protective efficacy.

Zhonghua Min Guo Wei Sheng Wu Ji Mian Yi Xue Za Zhi, 1992 Nov, 25(4), 270 - 5
Cryptococcus albidus isolated from pigeon excreta in Taiwan; Jen TM; Cryptococcus albidus (Saito) Skinner, found frequently in the air of El-Minia, Egypt; in New Zealand and Budapest, and isolated occasionally from clinical specimens, has now been recognized as the cause of human diseases . Since isolation of this fungus from pigeon droppings has not previously been reported, this first paper reports results of its drug-susceptibility testing to gentamicin and 5-fluorocytosine, as well as its fungal cell antigenic cross reactivity with C . neoformans as detected by a Latex-Crypto-Antigen Detection System (LCAS).

Acta Otorhinolaryngol Ital, 1992 Nov-Dec, 12(6), 605 - 10
{Blastomycosis of the cervicofacial area: a review of the literature and case report}; Cavalot AL et al.; A literature review concerning blastomycosis has been conducted . The involvement of the head and neck area appears to be very unusual, on the basis of autoptic observations . The most common diagnostic and subsequent therapeutic mistakes are pointed out . A new case is described and its clinical appearance, symptoms, diagnostic work up and therapeutic approach are discussed . This case report is of interest for three reasons: the rarity of this disease in our country, the possibility of confusing a Blastomyces infection with a cryptococcal one {correction of criptococcosy} and finally the therapeutic response to a new drug, not yet commercialized in Italy.

Mycoses, 1992 Nov-Dec, 35(11-12), 289 - 92
Pathogenic fungi in human dwellings; Staib F; Airborne invasive fungal infections in various risk groups of people suffering from immunodeficiencies are an increasing problem for modern medicine . Because of the acute and rapid course of invasive infections, prevention is of principal significance . Such prevention mainly concerns the control of fungal spores in indoor air . In this connection the immediate environment offering ecological niches for growth and morphogenesis of infective particles of Aspergillus spp., Mucoraceae, Cryptococcus neoformans and some other yeast-like fungi is of main interest . The current problems of indoor air mycology, i.e . the epidemiology and ecology of pathogenic fungi in indoor air, can only be recognized and interpreted by centres routinely performing mycological diagnosis for all the various risk groups of patients . Models of specific surveillance of the most important fungal pathogens (e.g . Aspergillus spp . and Cryptococcus neoformans) in indoor air will be outlined and discussed.

J Infect Dis, 1992 Oct, 166(4), 866 - 73
Binding of unopsonized Cryptococcus neoformans by human bronchoalveolar macrophages: inhibition by a large-molecular-size serum component; Levitz SM et al.; Infection with Cryptococcus neoformans usually begins after inhalation of airborne organisms . Since levels of opsonins in the alveolar space may be low, the ability of human bronchoalveolar macrophages to bind C . neoformans in the presence and absence of opsonins was studied . Bronchoalveolar macrophages bound unopsonized C . neoformans . Surprisingly, component(s) in pooled human serum (PHS) inhibited binding, as evidenced by 26% and 71% inhibition of binding when 20% PHS and heat-inactivated PHS (HI-PHS), respectively, were added to the system . Separation of PHS by molecular size revealed that the inhibitory component had an apparent molecular weight greater than 10(6) and was inhibitory at nanomolar concentrations . PHS stimulated and HI-PHS had no effect on binding of acapsular C . neoformans and zymosan particles to bronchoalveolar macrophages . These data demonstrate that bronchoalveolar macrophages can bind unopsonized, encapsulated C . neoformans, but that serum component(s) inhibits binding.

Med Trop (Mars), 1992 Oct-Dec, 52(4), 435 - 8
{Cryptococcosis caused by Cryptococcus neoformans var . Gattii . A case associated with acquired immunodeficiency syndrome (AIDS) in Kinshasa, Zaire}; Muyembe Tamfum JJ et al.; Since the introduction of AIDS, the biovar neoformans of Cryptococcus neoformans has replaced the biovar gattii as the predominant agent of cryptococcal meningitis in Kinshasa and in other tropical areas . That this is not an absolute rule is demonstrated by the present case of a HIV-positive patient, observed at the Kinshasa University Hospital, with cryptococcal meningitis due to the biovar gattii . Only four cases of this association have been published before . The authors conclude that both biovars are capable of infecting HIV-positive patients but that the apparent decline of the biovar gattii is related to the rarity of its natural reservoir in the urban environment, where the AIDS epidemic is concentratedPIP: In July 1990 in Zaire, a 36-year-old man was admitted to the University Clinic in Kinshasa for intense headaches, fever, vertigo, vision troubles, hallucinations, and irregular speech . He exhibited moderate wasting, left facial paralysis, and prurigo spots on the legs . Laboratory examinations revealed HIV seropositivity, antibodies to cryptococci, protein in the cerebrospinal fluid, and glucose in the cerebrospinal fluid . He was placed on 400 mg/d fluconazole . He died on August 4, two days after slipping into a coma . Cryptococcus neoformans var . gattii was isolated . The man had lived in a free union with two women . One died in 1989 of an illness characterized by persistent fever, considerable wasting, and pulmonary tuberculosis . The other woman is still alive although often having febrile episodes . She is HIV seropositive . Before AIDS arrived, cryptococcosis was rare in Zaire and Cryptococcus neoformans var . gattii was the most common etiologic agent . With AIDS, cryptococcosis has become an opportunistic infection . Since 1983, all cryptococcosis cases at the university clinics were a complication of AIDS . Cryptococcus neoformans var . neoformans was the etiologic agent in all these cases . It is possible that exposure to neoformans variety is more common than exposure to gattii variety . It is therefore an epidemiologic problem intimately associated with the geographic topography specific to ecological niches of these two varieties . Neoformans variety is found in pigeon droppings, while gattii variety has never been found in bird droppings . Gattii's natural host is the eucalyptus tree, found in Zaire . The case lived 400 m from a eucalyptus plantation . He was the only gattii variety cryptococcosis case in 1990-1991 among the 49 cryptococcosis cases at the Kinshasa University Clinics . In conclusion, gattii variety rarely causes cryptococcosis among AIDS patients because its natural reservoir is rare in urban areas where the AIDS epidemic is centered .

Mycopathologia, 1992 Oct, 120(1), 23 - 8
Immunodeficiency secondary to juvenile paracoccidioidomycosis: associated infections; Shikanai-Yasuda MA et al.; Four patients with acute paracoccidioidomycosis, hypoalbuminemia, ascites and associated infections are reported . They have been admitted to hospital 35 times, 4 of them due to active paracoccidioidomycosis, 14 to associated infections, 14 to ascites, edema and diarrhoea and 3 to herniorrhaphy . Two of them recovered after sepsis and central nervous system, muscular and subcutaneous cryptococcosis . The remaining two died . One had infectious diarrhoea (S . flexneri), peritoneal tuberculosis and sepsis (S . epidermidis); the other had bacterial meningitis, erysipelas, beta-hemolytic Streptococcus sepsis and miliary tuberculosis . Their immunodeficiency was attributed to enteric protein loss and/or malabsorption and malnutrition and was recognized by reduced response to delayed hypersensitivity skin tests in four patients and hypogammaglobulinemia in three of them . The authors discuss the need for prospective studies to be carried out, aiming at the mechanisms involved in secondary infections . Alternatives for maintaining the patients' adequate nutritional state should be investigated, to guarantee proper immune response and thus the ability to control intervening infections in patients with juvenile paracoccidioidomycosis.

Neuropathol Appl Neurobiol, 1992 Oct, 18(5), 478 - 88
Pathology of the central nervous system in patients infected with the human immunodeficiency virus (HIV): a report of 252 autopsy cases from Brazil; Chimelli L et al.; The central nervous system (CNS) was studied in 252 HIV-infected patients from the States of Rio de Janeiro and Sao Paulo in Brazil, the regions with the highest incidence of AIDS in the country . We compared the frequency and morphology of opportunistic infections and CNS changes caused by the HIV, with those described in other series and briefly analysed the risk factors involved in our cases . There were CNS lesions in 230 cases (91.3%), 30 (11.9%) with multiple infections and/or tumours . Most infections were opportunistic (65.4%), including 15.4% viral and 50% bacterial, fungal or protozoal infections . The most frequent was toxoplasmosis (34.1%), followed by cryptococcosis (13.5%), cytomegalovirus (CMV) infection (7.9%) and nodular encephalitis (6.7%) . Primary lymphomas were observed in 4% of the cases and HIV encephalitis or leukoencephalopathy in 10.7% . Other opportunistic and HIV associated lesions were present in a limited number of cases and there were also vascular and non-specific lesions . Our study confirms the high frequency of CNS lesions in HIV infected patients . They are morphologically similar to those previously described . However, the higher incidence of toxoplasmosis and cryptococcosis, a lower incidence of viral opportunistic and HIV-associated lesions, and the presence of rarer lesions such as histoplasmosis and chagasic encephalitis, differ from other series, and may reflect geographical and/or socio-economic factors.

J Acquir Immune Defic Syndr, 1992 Oct, 5(10), 978 - 87
Variations in inpatient mortality for AIDS in a national sample of hospitals; Turner BJ et al.; In this project, we examined the spectrum of AIDS-related conditions and variations in associated inpatient mortality for AIDS patients treated in a national sample of hospitals . We identified 10,538 adult discharges with a diagnosis indicating AIDS from 258 hospitals from a national sample of 438 acute-care hospitals with 6 million discharges in 1986-1987 . Opportunistic and other infections occurred in 55.9 and 37.9%, respectively, of AIDS discharges, and inpatient fatality rates varied considerably depending on complication type(s) and comorbidities . Clinical conditions were more important predictors of inpatient death than demographic or treatment site characteristics . Among opportunistic infections, odds of inpatient death were significantly increased for progressive multifocal leukoencephalopathy (odds ratio {OR} = 2.8), Pneumocystis carinii pneumonia (OR = 2.4), cryptococcosis (OR = 1.6), atypical mycobacterial infections (OR = 1.6), and toxoplasmosis (OR = 1.3) . Odds of inpatient death were also significantly increased by non-AIDS-defining infections causing septicemia (OR = 3.1) or CNS involvement (OR = 1.6) or pulmonary involvement (OR = 1.5) . After controlling for clinical conditions, significant differences in odds of death persisted across regions, age, and ethnic groups . Increases in hospitals' AIDS treatment experience were associated with a significant decrease in odds of inpatient death . These analyses provide a national perspective on the diversity of AIDS-related clinical conditions and their relative effects on inpatient mortality.

Clin Radiol, 1992 Oct, 46(4), 292 - 4
Case report: complete lung collapse--an unusual presentation of cryptococcosis; Carter EA et al.; Cryptococcosis presenting as an intrabronchial mass is not a recognized cause of complete lung collapse . This case report illustrates this extremely rare manifestation of pulmonary cryptococcosis, which mimicked primary pulmonary carcinoma clinically, radiologically and bronchoscopically.

Clin Infect Dis, 1992 Oct, 15(4), 704 - 6
Meningitis due to Prototheca wickerhamii in a patient with AIDS; Kaminski ZC et al.; The first documented case of algal meningitis due to Prototheca wickerhamii is reported in a patient with AIDS . The initial CSF culture yielded only Cryptococcus neoformans . P . wickerhamii was isolated on four subsequent lumbar punctures . The patient died, and at autopsy the alga was isolated from leptomeninges over the brain and about the spinal cord . Histologic sections from numerous locations of the brain revealed masses of cryptococci and prototheca.

J Neurosci Nurs, 1992 Oct, 24(5), 265 - 8
Cryptococcal meningitis in patients with AIDS; Mocsny N; In the U.S., cryptococcal meningitis is the most common form of fungal meningitis and a major cause of morbidity and mortality among immuno-suppressed patients . In the AIDS patient, cryptococcal meningitis often presents with fever and headache and is best treated with intravenous amphotericin B and oral flucytosine, or fluconazole . However, toxic effects may result from the therapy . This disease frequently relapses necessitating life-long treatment to prevent reactivation . Essential management principles focusing upon health education are presented to promote comprehensive nursing care for patients testing positive for the human immunodeficiency virus who also have cryptococcal meningitis.

J Clin Microbiol, 1992 Oct, 30(10), 2544 - 50
Evaluation of a monoclonal antibody-based latex agglutination test for diagnosis of cryptococcosis: comparison with two tests using polyclonal antibodies; Temstet A et al.; Cryptococcal antigen detection has become a routine biological test performed for patients with AIDS . The poor prognosis of cryptococcosis explains the need for reliable tests . We evaluated the performances of a newly commercialized agglutination test that uses a monoclonal antibody specific for cryptococcal capsular polysaccharide (Pastorex Cryptococcus; Sanofi-Diagnostics Pasteur, Marnes-la-Coquette, France) and compared them with those of tests that use polyclonal immune sera (Cryptococcal Antigen Latex Agglutination System, Meridian Diagnostics, Inc., Cincinnati, Ohio; and Crypto-LA, International Biological Labs Inc., Cranbury, N.J.) . The sensitivities and specificities of the tests were compared by using purified polysaccharides and yeast suspensions . Clinical specimens (131 serum samples, 41 cerebrospinal fluid samples, 34 urine samples, and 19 bronchoalveolar lavage samples) from 87 human immunodeficiency virus-positive subjects with (40 patients) and without (47 patients) culture-proven cryptococcosis were retrospectively tested during a blinded study . The effect of pronase treatment of samples was assessed for Pastorex Cryptococcus and the Cryptococcal Antigen Latex Agglutination System, and the antigen titers were compared . Our results show that (i) during the screening, concordance among the three tests was 97%; (ii) the use of pronase enhanced both the sensitivities and specificities of the Pastorex Cryptococcus test; (iii) titers agreed for 67% of the cerebrospinal fluid samples and 60% of the serum samples; and (iv) cryptococcosis was detected equally well with Pastorex Cryptococcus and with the other tests, whatever the infecting serotype (A, B, or D) . The meaning of in vitro sensitivity and the relationship between titers and sensitivity are discussed . The results show that Pastorex Cryptococcus is a rapid and reliable test for the detection of cryptococcal antigen in body fluids and suggest that kits cannot be used interchangeably to monitor antigen titers in patients.

Infect Immun, 1992 Oct, 60(10), 4080 - 7
The glucuronoxylomannan of Cryptococcus neoformans serotype A is a type 2 T-cell-independent antigen; Sundstrom JB et al.; The humoral immune response of inbred mice to immunization with the glucuronoxylomannan (GXM) of Cryptococcus neoformans was investigated both serologically and in plaque-forming cells (PFCs) . The T-helper-cell-independent quality of the GXM was demonstrated by using BALB/c nu/nu mice . Primary and secondary dose responses to three antigenic forms of GXM, (i) the native antigen, (ii) a GXM-bovine serum albumin protein conjugate, and (iii) a cryptococcal whole-cell vaccine, revealed a lack of isotype class switching and anamnestic responses . Both the levels of complement-fixing anti-GXM antibody in serum and the PFC responses in the athymic mice showed no significant differences from those in the wild-type controls . However, T cells are involved in the suppression of the primary response to GXM . When BALB/cBy mice were given rabbit anti-mouse thymocyte serum along with 0.5 microgram of GXM, both antibody levels in serum and PFC responses were significantly increased over those of control mice that received GXM and normal rabbit serum . In addition, T cells were also shown to enhance the primary immune response to GXM . BALB/cBy mice were given GXM and anti-mouse thymocyte serum on day 1 . On day 2, the experimental group was given anti-mouse thymocyte serum and the control group was given saline . On day 5, comparison of the PFC responses and anti-GXM antibody titers of the two groups revealed a significant increase in the immune response of the control over the experimental group . The type 2 T-cell-independent quality of GXM was also demonstrated in CBA/cHN xid mice . These mice lack the Lyb+ subset of B cells and are unable to respond to type 2 T-independent antigens but respond normally to type 1 T-independent antigens . Type III pneumococcal polysaccharide, a type 2 T-independent antigen, was used as a negative control, and trinitrophenyl-lipopolysaccharide, a type 1 T-independent antigen, was used as a positive control . The CBA/cHN xid mice failed to respond to either type III pneumococcal polysaccharide or GXM but did not respond to immunization with trinitrophenyl-lipopolysaccharide . BALB/cBy mice responded normally to all three antigens.

Hum Pathol, 1992 Oct, 23(10), 1106 - 14
Neuropathology of the spinal cord in the acquired immunodeficiency syndrome; Henin D et al.; The neuropathologic findings in the spinal cord were reviewed in 138 consecutive autopsies of patients with the acquired immunodeficiency syndrome . In all cases both the brain and spinal cord were examined by conventional histologic techniques, and in 63 cases immunohistochemistry was used to detect human immunodeficiency virus (HIV), Toxoplasma gondii, cytomegalovirus, and JC papovavirus antigens . The most common observation was a normal spinal cord (60%) . Vacuolar myelopathy (VM) was observed in 23 (17%) cases . Human immunodeficiency virus myelitis was evident in 8% of cases . Human immunodeficiency virus myelitis was associated with HIV encephalitis in 65% of the cases . Opportunistic infections of the spinal cord were uncommon, consisting of cryptococcosis (five cases), cytomegalovirus (four cases), toxoplasmosis (one case), and progressive multifocal leukoencephalopathy (one case), and almost always were seen with cerebral and/or systemic infection by these agents . Malignant lymphoma rarely involved the spinal cord (four cases); all were B-cell lymphomas and were associated with cerebral and/or systemic lymphoma . Other abnormalities rarely observed were Wallerian degeneration of the corticospinal tracts or posterior columns (6%) and focal microinfarcts . Most cases of VM (78%) were not associated with HIV myelitis, and in the five patients with both VM and HIV myelitis, HIV-infected cells were not found in the regions affected by VM . In contrast, 65% of cases with VM were associated with HIV encephalitis . The pathogenesis of VM remains unknown; it is probably not due to direct infection by HIV.

Rev Latinoam Microbiol, 1992 Oct-Dec, 34(4), 259 - 65
{Biological features and experimental pathogenicity of Candida strains isolated by hemoculture at the Hospital Infantil de México "Federico Gómez"}; Ramirez Aguilar ML et al.; In a period of 15 months (1990-1991) it was carried out 5781 blood cultures in which 180 strains of yeast-like were isolated . 116 of these strains were selected for biochemical classification, cellular and colonial morphology and experimental determination of virulence in mice . Most of the strains were classified as Candida albicans (60%) and the others were C . tropicalis (15.5%); C . guillermondii (10.3%); T . glabrata (6.8%); Rhodotorula rubra (3.4%); Cryptococcus neoformans (2.58%) y C . parapsilosis (0.86%) . C . albicans ATCC14053, y C . tropicalis ATCC14056 and T . glabrata ATCC15545 were employed as controls . The virulence test was performed using mice of 20-30 gr (4-6 weeks age) by intravenous injection in caudal vein with 0.5 ml of different suspension from 10(5) to 10(9) CFU/ml . Observation time was 10 days . Target organ was kidney by macro and microscopic observation of micro-abscess death . LD50 was estimated by the Reed-muench method . Intraspecific and interspecific differences were observed . It is more valid if we take into account that the experiment was done in homogenous population of host without risk factor which influences the human population in hospitals . Experimental virulence was compared with the evolution of diseases in the human host of which the strain was isolated.

Rev Soc Bras Med Trop, 1992 Oct-Dec, 25(4), 241 - 6
{A retrospective therapeutic study of neurocryptococcosis in 112 AIDS and non-AIDS patients}; de Campos EP et al.; A total of 112 AIDS and no AIDS cryptococcosis patients admitted at Emilio Ribas Hospital--Sao Paulo, Brazil, were treated with amphotericin B (AMB) or amphotericin B and 5 fluorocytosine (5FC) . Age, race, predisposing and epidemiological factors, respiratory symptoms were evaluated . Goodman tests applied in three patients groups (I, II and III) with associate or unique therapy revealed: 1 . prognostic factors: leukocytes ang glucose showed similar response in groups I, II and III and protein spinal fluid after 1.5g/AMB; 2 . India ink tests and Cryptococcus culture were often positive until 1.0g/AMB; 3 . significant hypokalemia during monotherapy . Hypo and hyperkalemia had similar data in associate therapy; 4 . significant difference in adverse reactions often appeared above 0.7g AMB/250g 5FC; 5 . early and late death were common in group III (unique) and group I (no AIDS) and III (2.5 to 4.0g) respectively; 6 . similar remission and deaths were verified in AIDS/cryptococcosis . Conclusions: adverse reactions were observed above 0.75g/AMB plus 250g 5FC . Association was important in initial therapy and AMB maintenance permitted late relapses.

J Med Assoc Thai, 1992 Oct, 75(10), 606 - 8
Itraconazole in cryptococcal meningitis in pregnancy: a case report; Chotmongkol V et al.; A 25-year-old pregnant women with cryptococcal meningitis treated with itraconazole during the first few weeks and 12th-16th week of pregnancy is reported . She delivered a normal baby . Itraconazole should be another drug for treatment of fungal infection in pregnancy.

East Afr Med J, 1992 Oct, 69(10), 550 - 3
World Health Organization clinical case definition for AIDS in Africa: an analysis of evaluations; Keou FX et al.; In 1985 at a World Health Organization (WHO) workshop on AIDS in Bangui, Central African Republic, a clinical case definition of Acquired Immune Deficiency Syndrome (AIDS) was developed for developing countries, such as sub-Saharan Africa, where sophisticated diagnostic equipment is not widely available . A particular cachectic syndrome, the "slim disease", which is highly suggestive of AIDS in Africa, constitutes the substratum for the clinical definition for AIDS . The WHO/Bangui definition in adults has a sensitivity of 60%, a specificity of 90%, and a high predictive value especially in endemic areas . The WHO/Bangui clinical case definition for paediatric AIDS is less easy to use in practice . Its low sensitivity (about 35%) is in relation to its incapacity to diagnose many of the frequently observed secondary infection for paediatric AIDS according to the CDC criteria . The WHO/Bangui clinical definition for AIDS seems to be convenient for epidemiological surveillance of the HIV epidemic in Africa . Nevertheless, the low sensitivity and the low specificity result in the failure to detect some cases of full blown AIDSPIP: In 1985, at a WHO workshop on AIDS in Bangui, Central African Republic, a clinical case definition of AIDS was developed for developing countries . This 1st definition contained 4 major criteria (chronic asthenia, major weight loss, chronic fever, and chronic diarrhea) and 6 minor criteria (chronic cough, persistent lymphadenopathy, herpes zoster, recurrent herpetic infection, pruritic dermatitis, and oropharyngeal candidiasis) . Kaposi's sarcoma and cryptococcal meningitis were sufficient by themselves for the diagnosis of AIDS . In children, the temporary definition of AIDS consisted of 3 major clinical criteria (weight loss and/or abnormally slow growth, chronic diarrhea lasting more than 1 month, and fever lasting more than 1 month), and 6 secondary clinical criteria (generalized lymphadenopathy, oropharyngeal candidiasis, repeated common infections such as otitis and pharyngitis, persistent cough, generalized pruritic dermatitis, and confirmed maternal HIV infection) . The revised Bangui definition was evaluated in 174 adult patients hospitalized at the Mama Yemo Hospital of Kinshasa, Zaire . 46% of 174 patients met the criteria of the WHO/Bangui definition . Overall, the sensitivity of the definition for HIV-1 infection was 59%, the specificity was 90%, and the positive predictive value (PPV) was 74% . However, the clinical case definition of African AIDS lacks specificity when it is applied to patients suffering from cachectic syndromes . The Bangui definition was also evaluated at the pediatric ward of Mama Yemo Hospital with 159 hospitalized children whose mean age was 33 months . 21 (13%) were infected by HIV-1 . The sensitivity of the definition was 35%, its specificity was 86%, and its PPV was 26% . Although the specificity was relatively high, the low values of sensitivity and PPV underline the weakness of the Bangui clinical case definition for diagnosing pediatric AIDS cases .

Leuk Lymphoma, 1992 Oct, 8(3), 213 - 20
Treatment of AIDS-related non-Hodgkin's lymphoma with a twelve week chemotherapy program; Sawka CA et al.; Current treatment options for acquired-immunodeficiency syndrome (AIDS)-related non-Hodgkin's lymphoma (NHL) are unsatisfactory because of excessive toxicity rates and frequent recurrence of lymphoma . In this phase II study, we evaluated a novel 12 week chemotherapy program with respect to feasibility, toxicity and therapeutic results . Thirty HIV-seropositive patients with intermediate grade or small non-cleaved cell NHL received a 12 week program of weekly intravenous and oral chemotherapy consisting of etoposide, adriamycin, cyclophosphamide, bleomycin, vincristine, methotrexate and prednisone as well as biweekly intrathecal cytosine arabinoside . Prophylaxis against Pneumocystis carinii pneumonia (PCP) and candida were given routinely . The overall objective response rate was 73% with 33% complete responders . The time to progression for those stable or responding was 9.4 months . Five of 10 complete responders are well and free of disease 13.2 to 24.5 months from diagnosis . Median survival for the 30 patients was 8.1 months . NHL was the most common cause of death (13/22); opportunistic infection caused only one death (cryptococcal meningitis) . Only 1 case of PCP occurred . The major toxicity was neutropenia . In conclusion this regimen resulted in response rates similar to other reports with acceptable toxicity and a very low incidence of PCP . Relapse of NHL remains a major challenge, however, and further studies are needed . Routine PCP prophylaxis should be incorporated into new trials of therapy for AIDS-related NHL.

J Immunol Methods, 1992 Sep 18, 154(1), 27 - 35
Monoclonal antibody based ELISAs for cryptococcal polysaccharide; Casadevall A et al.; Mouse monoclonal antibody (MAb)-based enzyme-linked immunosorbent assays (ELISAs) have been developed to detect Cryptococcus neoformans capsular polysaccharide from the four serotypes A, B, C and D . The ELISAs avoid the problem of unreliable polysaccharide binding to polystyrene plates by using MAbs to capture and immobilize the polysaccharide antigen . The presence of polysaccharide is detected using MAbs of a different isotype from that of the capture MAb . The capturing MAbs are themselves immobilized on the plates using commercial goat anti-mouse polyclonal sera . The MAbs bind to the glucuronoxylomannan component of cryptococcal polysaccharide . The ELISAs can be used to measure the concentration of polysaccharide in biological fluids and are potentially useful tools for basic research and clinical studies.

Med Klin (Munich), 1992 Sep 15, 87(9), 454 - 9
{Clinical diagnosis and neuropathologic examination findings in 20 AIDS patients}; van Lunzen J et al.; Disorders of the central nervous system (CNS) associated with HIV infections are becoming increasingly important in the area of clinical diagnosis and treatment of patients with AIDS . The aim of this retrospective analysis of 20 patients with AIDS who died in 1989 was to compare clinical diagnosis, neuroradiological findings and treatment with the results of neuropathological studies . The neuropathological examinations revealed primary CNS lymphoma (high-grade non-Hodgkin's lymphoma) in seven cases, cerebral toxoplasmosis in four cases, haemorrhagic infarction in three cases, cerebral cryptococcosis in three cases, and one case each of infiltration of the dura by a peripheral Burkitt's lymphoma, cytomegalovirus encephalitis and bacterial meningitis . A remarkably high percentage of CNS lymphomas with no distinct clinical or neuroradiological differentiation criteria were found in this study . On the basis of these data, we conclude that stereotactic biopsy and histological diagnosis should be recommended for patients with focal intracerebral lesions who fail to respond to suitable anti-parasitic treatment.

J Thorac Imaging, 1992 Sep, 7(4), 51 - 5
Pulmonary cryptococcosis; Patz EF Jr et al.; Cryptococcus neoformans is a ubiquitous soil fungus that rarely causes pneumonia in normal hosts but is a common cause of opportunistic infection . Pulmonary disease is initiated by inhalation of the organism, and a spectrum of radiographic manifestations can be seen . The most common finding is a poorly marginated nodule or mass . Lobar or segmental parenchymal opacities and, less commonly, a diffuse scattered nodular or reticulonodular pattern have also been observed . Associated adenopathy, pleural effusions, and cavitation are uncommon; when present, these are more common in immunocompromised patients . Establishing the diagnosis can be difficult, but pulmonary cryptococcosis should be considered in the differential diagnosis of patients in the proper clinical setting and with compatible radiographic findings.

J Thorac Imaging, 1992 Sep, 7(4), 12 - 22
Clinical manifestations of pulmonary fungal infections; Boyars MC et al.; Coccidioidomycosis, histoplasmosis, cryptococcosis, and blastomycosis are the most common deep pulmonary fungal infections encountered by the clinician . Each has a particular environmental habitat . As world travel increases, exposure to these infections becomes increasingly more common . The article reviews the microbiology, natural history, and clinical and laboratory findings of these diseases . Treatment options for these infections also are discussed.

Carbohydr Res, 1992 Sep 2, 233, 205 - 18
Structural variability in the glucuronoxylomannan of Cryptococcus neoformans serotype A isolates determined by 13C NMR spectroscopy; Turner SH et al.; Cryptococcus neoformans, the etiologic agent of cryptococcal meningoencephalitis, produces glucuronoxylomannan (GXM) as the major capsule component . Purified GXMs obtained from eight serotype A isolates of C . neoformans were treated by ultrasonic irradiation and then O-deacetylated prior to their comprehensive chemical analysis by GLC, GLC-MS, and 13C NMR spectroscopy . The average xylose: mannose: glucuronic acid molar ratio of the eight isolates is 1.96 +/- 0.25: 3.00: 0.58 +/- 0.10 . Methylation analyses and 13C NMR spectroscopy show a general structure for GXM that is comprised of a linear (1----3)-alpha-D-mannopyranan substituted with beta-D-GlcpA and with beta-D-Xylp at O-2 . Variable quantities of unsubstituted (1----3)-alpha-D-Manp were observed between the eight isolates studied . In several isolates some of the (1----3)-alpha-D-Manp residues are disubstituted with beta-D-GlcpA at O-2 and with beta-D-Xylp at O-4; this type of substitution was not previously thought to occur in serotype A isolates . Heterogeneity, between isolates, in the disposition of the substituents along the mannopyranan backbone was revealed by 13C NMR spectroscopy . The eight isolates, and three isolates previously studied, were each assigned to one of four distinct groups based on the 13C NMR chemical shifts of the anomeric carbons . Six of the eleven isolates gave identical spectra (Group I) . The six major anomeric resonances from Group I were assigned to specific glycosidic linkages present in GXM . The remaining five isolates gave more complex spectra that are indicative of additional linkages and comprise the remaining three groups . Three of these five isolates contain substantial amounts of linkages previously thought to be distinctive of serotypes B and C, i.e., Manp residues that are 4-O-glycosylated with beta-D-Xylp . Methylation analyses only predicted an average repeating unit, whereas 13C NMR spectroscopy demonstrated that GXM from each isolate may be categorized into four groups by the occurrence of distinct sequences of carbohydrate residues.

Vet Clin North Am Small Anim Pract, 1992 Sep, 22(5), 1119 - 32
Fungal diseases of the nasal cavity of the dog and cat; Wolf AM; Fungal infections of the nasal cavity are a common cause of nasal disease in the dog and cat . Aspergillus fumigatus most commonly affects the dog; Cryptococcus neoformans is the most common fungus isolated from the cat . Rhinosporidium infection causes obstructive nasal polyps in the dog but has not been reported in the cat . Several other miscellaneous fungi, including Exophiala, Alternaria, Trichosporon, Blastomyces, and Histoplasma, and the alga Prototheca occasionally cause nasal disease in dogs and cats.

J Urol, 1992 Sep, 148(3), 889 - 90
Cryptococcal prostatic abscess associated with the acquired immunodeficiency syndrome; Mamo GJ et al.; A case of cryptococcal prostatic abscess in a 28-year old man with the acquired immunodeficiency syndrome is presented . This is a unique presentation of a cryptococcal prostatic infection and of a prostatic abscess . The diagnosis and management are discussed, and the literature is reviewed.

Infect Immun, 1992 Sep, 60(9), 3937 - 9
In vivo complement activation and binding of C3 to encapsulated Cryptococcus neoformans; Truelsen K et al.; Tissues from mice infected with Cryptococcus neoformans were examined by immunofluorescence to determine the extent of deposition of complement component C3 on encapsulated cryptococci . The relative percentages of cryptococci in each tissue having readily visible C3 were greatest for liver and lung tissues, with the kidney tissue having the next highest percentage and the spleen having the lowest percentage . Binding of C3 fragments to cryptococci in brain tissue was essentially absent.

Infect Immun, 1992 Sep, 60(9), 3682 - 8
Experimental model of intracerebral infection with Cryptococcus neoformans: roles of phagocytes and opsonization; Blasi E et al.; A murine model of intracerebral (i.c.) infection with Cryptococcus neoformans in which naive mice receiving an i.c . fungal inoculation developed a severe disease has been established . The effect was strictly dependent on the number of microorganisms injected and evolved as lethal meningoencephalitis . Murine susceptibility to i.c . infection with C . neoformans was enhanced by treatment with chloroquine and colchicine, agents known to greatly affect the host phagocytic compartment . Furthermore, the life spans of both naive and drug-treated mice were significantly augmented when opsonized fungi were injected . Therefore, phagocyte-mediated mechanisms are likely involved in local resistance to i.c . infection with C . neoformans . Further support for this conclusion was supplied by in vitro data showing that microglial cells were proficient anticryptococcal effectors, provided opsonized microorganisms were used.

Infect Immun, 1992 Sep, 60(9), 3552 - 5
Heterogeneity of phenol oxidases in Cryptococcus neoformans; Ikeda R et al.; Phenol oxidase enzymes, linked to virulence in Cryptococcus neoformans, were prepared from broken cells . More enzyme activity was found in the ultracentrifugation supernatant; less was found in the membrane fraction . Phenol oxidases were located in acrylamide gel electropherograms by activity staining with L-dihydroxyphenylalanine (DOPA) . Mobility differences between soluble and solubilized membrane-bound phenol oxidases were not found . Comparison of enzymes produced at 25 and 37 degrees C revealed that the enzyme had lower activity and lower mobility at 37 degrees C . The mobility of 25 degrees C phenol oxidases from strains of C . neoformans var . gattii was lower than that of those from C . neoformans var . neoformans . Half of the phenol oxidase produced at 25 degrees C was bound by concanavalin A, while that produced at 37 degrees C was not bound . However, glucose starvation of cultures at 25 degrees C overnight resulted in increased amounts of enzyme which did not bind to concanavalin A . A given strain of C . neoformans produces different species of phenol oxidase under different culture conditions.

Nihon Kyobu Shikkan Gakkai Zasshi, 1992 Sep, 30(9), 1662 - 6
{Six cases of primary pulmonary cryptococcosis}; Nishii K et al.; Six patients with asymptomatic primary pulmonary Cryptococcosis are reported . In all of the patients, the disease was detected by annual chest X-ray during mass screening for lung cancer or during follow-up for pulmonary tuberculosis or gastric cancer . The chest X-ray findings consisted of a solitary pulmonary nodule in 4 patients and multiple pulmonary nodules in 2 . Only one patient who could not be histologically diagnosed by bronchofiberscopy underwent surgical resection . However, the other 5 patients were histologically diagnosed by transbronchial biopsy with bronchofiberscopy . They were treated with oral antifungal agents, namely flucytosine (5-FC) and/or fluconazole, with marked improvement of chest X-ray findings . These results indicate that transbronchial biopsy with bronchofiberscopy and oral administration of antifungal agents instead of initial surgical resection are useful in the diagnosis and treatment of primary pulmonary cryptococcosis.

Mycopathologia, 1992 Sep, 119(3), 133 - 6
Cryptococcus neoformans varieties as agents of cryptococcosis in Brazil; Rozenbaum R et al.; The study of the clinical isolates of Cryptococcus neoformans from 83 Brazilian patients with disseminated cryptococcosis showed that 75 were C . neoformans var . neoformans and 8 were var . gattii . Twenty-seven isolates were serotyped; all 19 var . neoformans were serotype A and all 8 var . gattii were serotype B . The correlation of the varieties of C . neoformans with the presence or not of hosts predisposing conditions to the mycosis showed that: (1) cryptococcosis caused by gattii variety occurred in 7 (58.3%) of the 12 nonimmunosuppressed patients, and (2) cryptococcosis caused by neoformans variety occurred in 65 (98.5%) of the 66 AIDS patients and in all 5 patients with other immunosuppressive conditions . The comparison of the distribution of the gattii and neoformans varieties between the nonimmunosuppressed and immunosuppressed patients showed a significant statistical difference (p < 0.01)PIP: 8 mycologists reviewed the medical records of 83 patients with disseminated crypttococcosis living in Brazil to examine the varieties of Cryptococcus neoformans . 12 patients were not immunosuppressed (group 1) . 65 patients had AIDS (group 2) . 5 patients either also had another disease and/or used immunosuppressive drugs (group 3) . Almost all the clinical isolates were from the cerebrospinal fluid and/or blood (80 isolates {96.4%} . C . neoformans var . gattii caused cryotococcosis in 58.3% (7) of the nonimmunosuppressed patients . C . neoformans var . neoformans was responsible for crypttococcosis in all but 1 of the AIDS patients (98.5%) and in all 5 patients who had another disease and/or used immunosuppressive drugs . 6 of the 8 cases with crypttococcosis caused by C . neoformans var . gatti lived in rural areas during their first 10 years . A statistically significant difference existed between the nonimmunosuppressed group (group 1) and the immunosuppressed patients (groups 2 and 3) in the comparison of the distribution of the gattii and neoformans varieties (p.01) . The omnipresence of C . neoformans var . neoformans, the urban population's regular exposure to C . neoformans var . neoformans, and predisposing conditions (i.e., immunosuppression) to crypttococcosis likely accounted for the neoformans variety mainly being the cause of crypttococcosis in areas in Brazil where C . neoformans var . gattii is indigenous .

Mycopathologia, 1992 Sep, 119(3), 129 - 32
Growth of Cryptococcus neoformans in a thiamine-free medium; Bruatto M et al.; The growth of Cryptococcus neoformans in a minimal liquid synthetic medium with or without thiamine (10 micrograms/ml) was investigated . In these media the presence or absence of thiamine had no effect on the development of C . neoformans . To check these results, we performed a series of experiments on a solid form of the minimal synthetic medium . In this study a series of six serial transfers were carried out to starve the cells of nutrients that may have been carried over from their growth on rich media . In each of the transfers on the solid synthetic medium, C . neoformans showed a similar and scarce growth . This finding indicates that C . neoformans could be autotrophic in respect to thiamine.

Intern Med, 1992 Sep, 31(9), 1132 - 6
Immunological studies on opportunistic infection and the development of adult T-cell leukemia; Tashiro T et al.; Three patients with opportunistic infection preceding adult T-cell leukemia (ATL) are presented: a 66-year-old woman with cryptococcosis and Pneumocystis carinii pneumonia, a 46-year-old man with Pneumocystis carinii pneumonia, and a 55-year-old woman with cryptococcosis . Although, at the first examination, the first two had smoldering type ATL and the third case was an HTLV-I carrier, all three developed overt ATL 14-16 months after the onset of opportunistic infection . It is considered that there is immune suppression already present in HTLV-I carriers and in patients with smoldering ATL, and opportunistic infection is predictive of the development of ATL.

AJNR Am J Neuroradiol, 1992 Sep-Oct, 13(5), 1477 - 86
AIDS-related CNS cryptococcosis: radiologic-pathologic correlation; Mathews VP et al.; PURPOSE: This study evaluates the effectiveness of cranial CT and MR in detecting autopsy findings of AIDS-related CNS cryptococcosis . METHODS: Final imaging studies compared with pathology were CT in eight patients (five with contrast) and MR in five patients (all with Gd-DTPA) . RESULTS: Neither modality effectively identified cryptococcal meningitis . Punctate hyperintensities were seen in all patients with MR and corresponded pathologically to both perivascular spaces dilated by cryptococcal infection and cryptococcomas . Pathologically, cryptococcomas were more common than dilated perivascular spaces . MR detected more cryptococcomas than did CT, but both modalities underestimated the number of lesions seen at autopsy . Contrast enhancement of cryptococcomas and cryptococcal meningitis was uncommon . CONCLUSIONS: CNS cryptococcosis was more effectively demonstrated by MR than by CT, but both modalities underestimated the pathologic extent of the disease . Cryptococcal lesion contrast enhancement was unusual possibly because of the immunocompromised state of our patients and the unique characteristics of the organism itself.

J Clin Pathol, 1992 Sep, 45(9), 836 - 7
New enzyme immunoassay for detecting cryptococcal antigen; Knight FR; Results obtained with a recently introduced enzyme immunoassay system (EIA) for the detection of cryptococcal antigen (Meridian Diagnostics Inc) were compared with those obtained by a latex agglutination (LA) method (Immuno-Mycologics, Norman, Oklahoma, USA) . Fifty four samples were examined . There was 92% agreement between the two methods . One false positive result was obtained with LA, and one sample was inevaluable . The EIA was rapid and simple to perform . There was some evidence that it gave fewer false positive reactions and improved the diagnosis of genuine early cases.

Rev Inst Med Trop Sao Paulo, 1992 Sep-Oct, 34(5), 383 - 7
Possibility of in-hospital infection by Cryptococcus neoformans in patients with AIDS; Rustan ME et al.; The objective of the present work was to carry out a survey of soil samples taken from different areas of a hospital of infectious disease located in the city of Cordoba, where three AIDS patients were hospitalized during different periods in the same ward . The three of them returned with meningeal cryptococcosis between three or five months after having been discharged . Cryptococcus neoformans was isolated in 8/10 samples collected outside the hospital, near the pigeon house . The samples collected from the AIDS patients ward and its surroundings were negative . These findings suggest that the patients may have been infected by the fungus during their first stay in hospital.

J Med Assoc Thai, 1992 Sep, 75(9), 548 - 50
Superior division paresis of the oculomotor nerve caused by cryptococcal meningitis; Chotmongkol V et al.; A case of cryptococcal meningitis with unilateral paresis of the superior division of the oculomotor nerve was reported . The ocular signs were completely improved by antifungal therapy . This case demonstrates that divisional oculomotor paresis occurred in the subarachnoid portion of the third cranial nerve before its anatomic bifurcation.

Therapie, 1992 Sep-Oct, 47(5), 403 - 7
{Drug-induced benign intracranial hypertension . Apropos of a case with amphotericin B . Review of the literature}; Heudier P et al.; Benign intracranial hypertension (BICH) is a rare adverse event . We report the case of a 31-year-old female drug addict who had been seropositive for HIV since 1987 . She had stage IV C1 AIDS, and was receiving intravenous amphotericin B for generalized cryptococcosis with no neuromeningeal involvement . She developed BICH that regressed when the antifungal drug was withdrawn and treatment for cerebral edema was started . BICH is a clinical entity involving intracranial hypertension with no focal neurological signs or detectable intracranial lesion . The manifestations include headache, transitory or permanent visual disturbances (diplopia, loss of visual acuity) and the perception of intracranial noise . The cerebrospinal fluid is under increased pressure but the composition is normal . The eye fundus examination shows papillary edema, and the neuroradiological workup is normal . BICH can only be diagnosed once an expansive intracranial process, neuromeningeal infection, and non-communicative hydrocephalus have been ruled out . In the majority of cases, no etiology is found . Such cases of idiopathic BICH usually occur in overweight young women, although drugs can be implicated . Amphotericin B has not previously been held responsible for BICH . On the basis of this observation, we present a review of the literature.

J Biol Chem, 1992 Aug 25, 267(24), 17159 - 69
4-oxatetradecanoic acid is fungicidal for Cryptococcus neoformans and inhibits replication of human immunodeficiency virus I; Langner CA et al.; Candida albicans and Cryptococcus neoformans are major causes of systemic fungal infections, particularly in patients with acquired immunodeficiency syndrome . Metabolic labeling studies revealed that these organisms synthesize a small number of N-myristoylproteins, the most prominent being 20-kDa ADP-ribosylation factors (Arfs) . C . albicans Arf has approximately 80% identity with the essential Arf1 and Arf2 proteins of Saccharomyces cerevisiae . {3H}Myristic acid analogs with oxygen for -CH2- substitutions at C4, C6, C11, and C13 are incorporated into cellular N-myristoylproteins, phospholipids, and neutral lipids produced by these three yeasts during exponential growth at 30 degrees C in complex media . Analog- and organism-specific differences in the efficiency of labeling of proteins and lipid classes were observed . The effects of oxatetradecanoic acids with oxygen for -CH2- substitutions at C3-C13 on C . neoformans, C . albicans, and S . cerevisiae were assessed during mid-log phase growth at 30 degrees C . A single dose of 3-oxa-, 4-oxa-, 5-oxa- or 6-oxatetradecanoic acid (O3-O6, final concentration = 300 microM) was able to inhibit growth of C . neoformans in the order O4 greater than O5 greater than O3 approximately O6 . The other compounds were inactive . 4-Oxatetradecanoic acid was fungicidal, producing a 10,000-fold reduction in viable cell number 1 h after administration and continued suppression of cell growth for 7 h . A clear dose response was observed over a concentration range of 100-300 microM . 4-Oxatridecanoic acid was 100-fold less potent in reducing cell viability than 4-oxatetradecanoic acid but more potent than 5-oxatridecanoic acid . O4 produced approximately 10-100-fold reductions in the viability of C . albicans and S . cerevisiae at 300-500 microM, respectively, whereas O5 and O6 were less active . Since N-myristoylation of the Pr55gag polyprotein precursor produced by human immunodeficiency virus I (HIV-I) is essential for its assembly, we also assessed the antiviral effects of 4-oxatetradecanoic acid . O4 is able to produce a 50% reduction in the replication of HIV-I in acutely infected human T-lymphocyte cell lines at a concentration of 18 microM . Together, these data suggest that (i) the position of the oxygen for methylene substitution is a critical determinant of the fungicidal activity of O4 and (ii) NMT may be an attractive therapeutic target for treating opportunistic fungal infections in patients infected with HIV-I.

Cancer, 1992 Aug 15, 70(4 Suppl), 959 - 65
New drugs for infections in patients with cancer; Hughes WT; BACKGROUND . During the past several years, the treatment and prevention of infections in patients with cancer have improved because of the development of new antimicrobial drugs . METHODS . A representative antibacterial, antifungal, and antiviral drug is discussed . RESULTS . The fluoroquinolone compounds, such as ciprofloxacin, norfloxacin, and ofloxacin, have broad spectrum bactericidal activity and have proved to be effective in both the treatment and prevention of certain infections in patients with cancer . The triazole drug fluconazole is useful in the treatment of oral, esophageal, and disseminated candidiasis and cryptococcal meningitis . Early studies suggest that a new acyclic nucleoside, ganciclovir, has some effect in the treatment of cytomegalovirus infections, but its precise use in patients with cancer has not been fully established . CONCLUSIONS . New drugs currently available to the practitioner will improve management of infections in patients with cancer, but none is totally effective and the search for new compounds must continue.

Gene, 1992 Aug 1, 117(1), 145 - 50
Cloning and expression in Escherichia coli of a xylanase-encoding gene from the yeast Cryptococcus albidus; Morosoli R et al.; In the yeast, Cryptococcus albidus, a comparison between the sequence of the xylanase (XLN)-encoding chromosomal gene (XLN) and the cDNA sequence reveals the presence of seven introns, ranging in length from 51 to 69 bp . One of their 5' splice site sequences is similar to the consensus sequence for yeast, while the other six resemble the consensus sequence for higher eukaryotes . Their 3' end splice site sequences are representative of the conserved sequence found in eukaryotes . Their putative branching point sequences are different from the well-known conserved sequence, 5'-TACTAAC, observed in yeast, but again resemble the mammalian one . The cDNA encoding XLN is expressed by Escherichia coli, under the control of the lacZ promoter . The gene product remains inside the cell and has a molecular size of 40 kDa, which matches the size of the nonglycosylated protein . When compared to the glycosylated enzyme, the nonglycosylated XLN from E . coli shows twofold less affinity for substrate and its Vmax is 100-fold lower . Moreover, the nonglycosylated XLN only acts on large xylan polymers and very slightly on xylohexaose.

Infect Immun, 1992 Aug, 60(8), 3122 - 7
Kinetic analysis of the amplification phase for activation and binding of C3 to encapsulated and nonencapsulated Cryptococcus neoformans; Kozel TR et al.; Encapsulated and nonencapsulated cryptococci exhibit quantitative and qualitative differences in their activation of the complement system . We examined the kinetics for the rapid amplification phase in which C3 was activated and bound to encapsulated cryptococci, nonencapsulated cryptococci, and zymosan particles . Yeast cells were incubated in normal human serum containing 125I-labeled C3, and bound C3 fragments were measured after 1 to 64 min of incubation . A kinetic analysis showed that the apparent first-order rate constant (k') for binding of C3 to nonencapsulated cryptococci did not differ significantly from k' for binding of C3 to zymosan particles (P greater than 0.05) . However, the rate constant for binding of C3 to encapsulated cryptococci was significantly (P less than 0.001) greater than k' for binding of C3 to nonencapsulated cryptococci and zymosan particles . A plot of C3 molecules bound to encapsulated cryptococci versus time cubed was nearly linear, suggesting that accumulation of C3 in the cryptococcal capsule follows the kinetics predicted by an expanding sphere . In contrast, the plot of C3 molecules bound to nonencapsulated cryptococci or zymosan particles against time was nearly linear, but those plots against time squared or time cubed were not . This result indicates that the rate-limiting step for the addition of C3 fragments to these latter yeast cells follows the kinetics of neither the perimeter of an expanding circle nor the surface of an expanding sphere . Taken together, the results indicate that the high rate of accumulation of C3 in the cryptococcal capsule is consistent with the expected geometry of an expanding sphere of bound C3 within the three-dimensional matrix of the capsule.

J Oral Pathol Med, 1992 Aug, 21(7), 289 - 94
Orofacial manifestations of the systemic mycoses; Scully C et al.; Aspergillosis, cryptococcosis and zygomycosis (mucormycosis) are overall the most common systemic mycoses but histoplasmosis is particularly endemic in parts of central USA and other areas worldwide . Orofacial lesions caused by systemic mycoses have rarely been reported in the past though they have been recorded particularly in outdoor workers from geographic areas with a high prevalence of infection and occasionally in immunocompromised individuals . Increasing world-wide travel, and the dramatic increase in numbers of immunocompromised persons, especially those with human immunodeficiency virus (HIV) disease, have been responsible for an increase in reports and other studies of orofacial disease in systemic mycoses and new opportunists are now being recognized . Those in Oral Medicine and Pathology must now be aware of the possibility of a systemic mycosis as the cause of chronic oral ulceration, chronic maxillary sinus infection, or bizarre mouth lesions, especially in patients with HIV disease, lymphoproliferative disorders, or diabetes mellitus, or in those who have been in endemic areas . Diagnosis and management should be undertaken in consultation with a physician with appropriate expertise, as pulmonary and other systemic infection may well be present . This paper reviews the eight main systemic mycoses.

Clin Infect Dis, 1992 Aug, 15(2), 211 - 22
Toxoplasmic encephalitis in AIDS; Luft BJ et al.; Involvement of the central nervous system (CNS) is common in patients with advanced disease due to human immunodeficiency virus (HIV) . Symptoms range from lethargy and apathy to coma, incoordination and ataxia to hemiparesis, loss of memory to severe dementia, and focal to major motor seizures . Involvement may be closely associated with HIV infection per se, as in the AIDS dementia complex, but is frequently caused by opportunistic pathogens such as Toxoplasma gondii and Cryptococcus neoformans or malignancies such as primary lymphoma of the CNS . The clinical presentations of attendant and direct CNS involvement are remarkably non-specific and overlapping, yet a correct diagnosis is critical to successful intervention . Toxoplasmic encephalitis is one of the most common and most treatable causes of AIDS-associated pathology of the CNS . A great deal has been learned in the last 10 years about its unique presentation in the HIV-infected patient with advanced disease . Drs . Benjamin J . Luft of the State University of New York at Stony Brook and Jack S . Remington of the Stanford University School of Medicine and Palo Alto Medical Foundation's Research Institute have studied T . gondii for many years and are two of the leading experts in the field . This commentary comprises an update of their initial review (J Infect Dis 1988;157:1-6) and a presentation of the current approaches to diagnosing and managing toxoplasmic encephalitis in HIV-infected patients.

Clin Pharm, 1992 Aug, 11(8), 705 - 13
Endocrine complications associated with human immunodeficiency virus infection; Etzel JV et al.; The causes and management of endocrine disorders associated with human immunodeficiency virus (HIV) infection are reviewed . Endocrine disorders observed in HIV-positive patients include adrenal abnormalities, hyporeninemic hypoaldosteronism, pituitary insufficiency, pancreatic abnormalities, thyroid and parathyroid disorders, and testicular abnormalities . Opportunistic pathogens implicated in these disorders include cytomegalovirus, Cryptococcus, Toxoplasma, mycobacteria, Candida, and Aspergillus . Neoplasma such as Kaposi's sarcoma and lymphoma can also cause endocrine abnormalities . Several drugs used in patients with the acquired immunodeficiency syndrome (AIDS) are associated with the development of endocrine disorders . These drugs include ketoconazole, itraconazole, rifampin, vidarabine, pentamidine, trimethoprim-sulfamethoxazole, didanosine, and ganciclovir . Severe patient debilitation can contribute to the development of endocrine abnormalities . Monitoring of adrenal gland function may be prudent in HIV-infected patients who have nonspecific symptoms of adrenal insufficiency . If adrenal insufficiency is diagnosed, replacement therapy with oral hydrocortisone is required . Administration of fludrocortisone can rapidly alleviate the signs and symptoms of hyporeninemic hypoaldosteronism . Fluid restriction is the first step in managing the pituitary abnormality known as the syndrome of inappropriate secretion of antidiuretic hormone . Drug-induced endocrine abnormalities often resolve after withdrawal of the offending agent . Endocrine complications in HIV-infected patients may be caused by infection, malignancy, or drugs . Adjusting or instituting drug therapy may be necessary to control symptomatic endocrine abnormalities.

Zhonghua Shen Jing Jing Shen Ke Za Zhi, 1992 Aug, 25(4), 240 - 2, 255
{Factors affecting prognosis of cryptococcal meningitis}; Cheng S; By analyzing 26 cases of clinic data in cryptococcal meningitis . The author found that the poor prognosis in cryptococcal meningitis depends on following factors: 1 . younger age of patients, 2 . abrupt onset, 3 . course prolonged over 6 weeks, 4 . complicated extracerebral cryptococcal infections and many underlying disease, 5 . used corticosteroids and antibiotics longtime, 6 . higher CSF pressure and lower CSF cells count most of which is neutrophilic leukocyte.

Antimicrob Agents Chemother, 1992 Aug, 36(8), 1648 - 57
In vitro antifungal activities and in vivo efficacies of 1,3-beta-D-glucan synthesis inhibitors L-671,329, L-646,991, tetrahydroechinocandin B, and L-687,781, a papulacandin; Bartizal K et al.; The in vivo anti-Candida activities of 1,3-beta-D-glucan synthesis inhibitors L-671,329, L-646,991 (cilofungin), L-687,901 (tetrahydroechinocandin B), and L-687,781 (a papulacandin analog) were evaluated by utilizing a murine model of disseminated candidiasis that has enhanced susceptibility to Candida albicans but increased sensitivity for discriminating antifungal efficacy . DBA/2 mice were challenged intravenously with 1 x 10(4) to 5 x 10(4) CFU of C . albicans MY1055 per mouse . Compounds were administered intraperitoneally at concentrations ranging from 1.25 to 10 mg/kg of body weight twice daily for 4 days . At 6 h and 1, 2, 3, 4, 7, and 9 days after challenge, five mice per group were sacrificed and their kidneys were homogenized and plated for enumeration of Candida organisms (CFU per gram) . Progressiveness of response trends and no-statistical-significance-of-trend doses were derived to rank compound efficacy . 1,3-beta-D-Glucan synthesis 50% inhibitory concentrations were determined by using a C . albicans (MY1208) membrane glucan assay . Candida and Cryptococcus neoformans MICs and minimal fungicidal concentrations were determined by broth microdilution . L-671,329, L-646,991, L-687,901, and L-687,781 showed similar 1,3-beta-D-glucan activities, with 50% inhibitory concentrations of 0.64, 1.30, 0.85, and 0.16 micrograms/ml, respectively . Data from in vitro antifungal susceptibility studies showed that L-671,329, L-646,991, and L-687,901 had similar MICs ranging from 0.5 to 1.0 micrograms/ml, while L-687,781 showed slightly higher MICs of 1.0 to 2.0 micrograms/ml for C . albicans MY1055 . Lipopeptide compounds were ineffective against C . neoformans strains.Results from in vivo experiments comparing significant trend and progressiveness in response analyses indicated that L-671,329 and L-646,991 were equipotent but slightly less active than L-687-901, while L-687,781 was ineffective at 10 mg/kg . Fungicidal activities of L-671,329, L-646,991, and L-687,901 were observed in vivo, with significant reduction in Candida CFU per gram of kidneys compared with those in sham-treated mice at doses of > or = 2.5 mg/kg evident as early as 1 day after challenge.

Semin Arthritis Rheum, 1992 Aug, 22(1), 18 - 24
Cryptococcal meningitis in systemic lupus erythematosus; Zimmermann B 3rd et al.; Two cases of cryptococcal meningitis occurring in patients with systemic lupus erythematosus (SLE) are presented, and 24 additional cases from the literature are reviewed . The insidious onset of this infrequent complication is emphasized . The nonspecific neurological findings associated with this infection are often mistakenly diagnosed as a central nervous system manifestation of SLE . Earlier diagnosis and effective antifungal therapy have improved the prognosis of cryptococcal meningitis in SLE patients in recent years . Strategies for the treatment of patients with this complication are discussed.

Biosci Biotechnol Biochem, 1992 Aug, 56(8), 1230 - 5
Cloning and molecular analysis of cDNA encoding a carboxymethylcellulase of the yeast Cryptococcus flavus; Cui Z et al.; A cDNA copy for carboxymethylcellulase (CMCase 1) of the yeast Cryptococcus flavus was cloned by screening an expression cDNA library with anti-CMCase 1 antibody . The sequence of the cDNA had an open reading frame of 1023 bp that encoded a preprotein of 341 amino acids with a molecular weight of 35,698 . The putative precursor begins with a hydrophobic segment that possibly acts as a signal sequence for secretion, which is followed by a presumed prosequence and a sequence consistent with the N-terminal amino acid sequence of secreted CMCase 1 . No potential N-glycosylation site was found in the sequence of putative pro-CMCase 1 . Comparison of the deduced protein sequence shows that the C . flavus CMCase 1 is partially homologous to the Trichoderma reesei endoglucanase EGIII . Alignment of the cDNA copy and the chromosomal DNA showed seven putative introns of 45 to 134 bp . When introduced into E . coli, the cDNA directed the synthesis of CMCase 1 as seen by CMCase activity and Western blotting using anti-CMCase 1 antibody.

Tijdschr Diergeneeskd, 1992 Jul 15, 117(14), 414 - 6
{Mycotic mastitis in cattle}; van Veen HS et al.; The literature on aetiology, diagnosis, symptoms, therapy and prognosis of mycotic mastitis in cows is reviewed . The importance of identification of the causative agent for the prognosis is discussed . Some cases of (candida) mastitis recover spontaneously: however, spontaneous recovery or recovery after therapy for mastitis caused by Cryptococcus or Prototheca is rare . Frequent milking of infected teats is important during treatment of mycotic mastitis . If supportive pharmacotherapy is desired, antimycotic drugs could be appropriate, however there is no clear evidence of the effectiveness of this therapy.

South Med J, 1992 Jul, 85(7), 762 - 4
Cryptococcosis of the larynx in a patient with AIDS: an unusual cause of fungal laryngitis; Browning DG et al.; We have presented a case of unsuspected cryptococcal laryngitis, clinically masquerading as Kaposi's sarcoma in a patient with AIDS . The spectrum of laryngeal disease in AIDS patients includes a variety of infections and neoplasms, which can be treated satisfactorily when accurate and timely diagnosis is made.

South Med J, 1992 Jul, 85(7), 700 - 2
Cavitary pulmonary cryptococcosis complicating Churg-Strauss vasculitis; Amundson DE; Churg-Strauss vasculitis (CSV) is an interesting but uncommon pulmonary vasculitis . Cavitation in CSV is distinctly unusual and should prompt a work-up for other causes . We have described a case of CSV complicated by pulmonary cryptococcosis, which was treated with a novel antifungal regimen.

Gene, 1992 Jul 1, 116(1), 109 - 13
Secretion of a Cryptococcus albidus xylanase in Saccharomyces cerevisiae; Moreau A et al.; The xylanase(XLN)-encoding gene(XLN) of Cryptococcus albidus and its cDNA were each inserted into the vector, pVT100, for expression in Saccharomyces cerevisiae . Expression was under the control of either their own promoter or the gene encoding alcohol dehydrogenase (ADH1) promoter . Yeast transformed with plasmids containing the cDNA of the structural XLN gene and the XLN promoter produced active extracellular XLN when grown with galactose as carbon source . However, with glucose as carbon source, XLN was repressed . Using the ADH1 promoter, which is stimulated by glucose, XLN was secreted into the culture medium . In both cases, the secreted 48-kDa enzyme corresponded to the native XLN produced by C . albidus . With the plasmid bearing the genomic XLN gene, there was transcription, but the seven introns interrupting XLN were not spliced out by S . cerevisiae and no enzyme was produced.

J Infect Dis, 1992 Jul, 166(1), 121 - 33
Experimental Trichosporon infection in persistently granulocytopenic rabbits: implications for pathogenesis, diagnosis, and treatment of an emerging opportunistic mycosis; Walsh TJ et al.; Disseminated Trichosporon infection, an uncommon but emerging opportunistic mycosis due to Trichosporon beigelii, is frequently difficult to diagnose, refractory to treatment, and associated with a high attributable mortality . Models of disseminated and gastrointestinal Trichosporon infection were developed in persistently granulocytopenic rabbits . The patterns of infection resembled those of clinical disease, including cutaneous lesions, chorioretinitis, renal infection, pulmonary infection, and antigenemia cross-reactive with cryptococcal capsular polysaccharide . Antigenemia, an early manifestation of disseminated Trichosporon infection, originated in vivo from a fibrillar extracellular matrix . Trichosporon organisms disseminated from the gastrointestinal tract to visceral tissue in colonized immunosuppressed rabbits, whereas there was no dissemination from the gastrointestinal tract of otherwise normal rabbits . The antifungal triazoles, fluconazole and SCH 39304, were most active; maximum tolerated doses of amphotericin B and liposomal amphotericin B were ineffective . Trichosporon antigenemia declined in response to antifungal therapy . These findings contribute to improved understanding of the pathogenesis, diagnosis, and treatment of disseminated Trichosporon infection.

Antimicrob Agents Chemother, 1992 Jul, 36(7), 1466 - 71
Aerosolized liposomal amphotericin B for treatment of pulmonary and systemic Cryptococcus neoformans infections in mice; Gilbert BE et al.; Cryptococcus infections of the lung and central nervous system have become major problems in immuno-compromised patients, leading to the need for additional treatment protocols . We have utilized a Cryptococcus-mouse model that mimics human cryptococcal disease to evaluate the efficacy of amphotericin B-liposomes (AmpB-Lip) when delivered by small-particle aerosol (SPA) . In the model, initial intranasal inoculation leads to a pulmonary infection that spreads after 2 to 3 weeks to distant organs, including the brain . Aerosols of AmpB-Lip that were generated by a Collison nebulizer had mass median aerodynamic diameters of 1.8 microns and contained 10.3 micrograms of AmpB per liter . When AmpB-Lip SPA was begun at 24 h postinoculation, a single 2-h treatment (0.3 mg of AmpB per kg of body weight) was effective in reducing pulmonary Cryptococcus infection . This regimen was more effective than intravenous administration of AmpB-Lip given for 3 continuous days . This single 2-h exposure to AmpB-Lip also was effective in reducing pulmonary Cryptococcus infection when treatment was delayed for 7 or 14 days . At day 21, when organisms had spread to the brain in all animals, the single 2-h aerosol treatment reduced the number of cryptococci in the brain as well as in the lungs . AmpB-Lip SPA administered once for 2 h on days 7, 14, and 21 also was effective in increasing the duration of survival of infected animals . These results demonstrate that aerosolized AmpB-Lip can be effective in treating both local, pulmonary Cryptococcus disease and systemic disease.

Ann Pharmacother, 1992 Jul-Aug, 26(7-8), 876 - 82
Parenteral and oral fluconazole for acute cryptococcal meningitis in AIDS: experience with thirteen patients; Stern JJ et al.; OBJECTIVE: Cryptococcus neoformans infections of the central nervous system affect up to ten percent of AIDS patients . Standard therapy with amphotericin B with or without 5-flucytosine has a high rate of failure, relapse, and toxicity . Fluconazole is a new triazole antifungal agent available in both oral and intravenous forms that has shown efficacy in the primary and maintenance treatment of cryptococcal meningitis in AIDS patients . In this open, noncomparative trial, we evaluated the safety and efficacy of intravenous fluconazole followed by oral fluconazole in the treatment of acute cryptococcal meningitis in AIDS patients . METHODS: Thirteen AIDS patients with acute cryptococcal meningitis, or relapse after successful primary therapy, received 400 mg of intravenous fluconazole daily for 12-16 days followed by oral fluconazole 400 mg/d for the duration of primary therapy . If cerebrospinal fluid (CSF) cultures converted to negative within 32 weeks of treatment, the fluconazole dose was decreased to 200 mg/d as maintenance therapy . RESULTS: Fluconazole therapy was successful in six patients (46 percent) and unsuccessful in seven (54 percent) . Of the seven patients considered unsuccessful, one demonstrated clinical improvement but remained CSF-culture positive, five were clinical failure and were switched to amphotericin B therapy, and one died after two weeks secondary to cryptococcal meningitis . No patient experienced any adverse reactions necessitating discontinuation of therapy . CONCLUSIONS: In this small group of patients, moderate doses of parenteral and oral fluconazole for acute cryptococcal meningitis in AIDS patients demonstrated failure rates similar to those reported in other studies with fluconazole and with amphotericin B . As there was no difference in initial Karnofsky scores or the severity of disease in treatment successes versus failures, it is difficult to determine who might respond to fluconazole as initial therapy or who should be treated initially with another agent . Further studies and clinical experience are needed.

Mycopathologia, 1992 Jul, 119(1), 11 - 6
Evaluation of the Pro-Lab ID ring system for the identification of medically important yeasts; Sekhon AS et al.; We evaluated 151 coded isolates of medically important yeast species belonging to the genera Candida, Cryptococcus, Geotrichum, Rhodoturula, Saccharomyces and Torulopsis using the newly developed rapid Pro-Lab Identification Ring, PL 960 system (PLID-Ring) . All isolates were concurrently identified by the API 20C and conventional procedures comprising macro- and micromorphology, assimilation and fermentation of various carbon and nitrogen compounds . The PLID-Ring system identified isolates of Candida albicans, C . kefyr, C . krusei, C . lusitaniae, C . parapsilosis, Rhodotorula rubra, and Torulopsis glabrata with 100% accuracy in 24 h . This system identified C guilliermondii and S . cerevisiae isolates with an accuracy of 90% and 86%, respectively, while those belonging to Cr . neoformans, T . candida (= C . famata), C . rugosa and C . tropicalis were identified with 38.4%, 50%, 12.5% and 50% accuracy, respectively . Three isolates of Cr . laurentii were not identified by the PLID-Ring system . The overall accuracy of the PLID-Ring system was 81.45% (123 of 151 isolates) . However, the system does not include species such as Cr . laurentii in its data base . When these three Cr . laurentii isolates were excluded from the evaluation, the accuracy of the PLID-Ring system increased from 81.45% to 83.1%.

Ethiop Med J, 1992 Jul, 30(3), 169 - 73
Cryptococcal meningitis in a young Ethiopian woman with AIDS; Gebremedhin A; The case of a 20 year old Ethiopian woman with cryptococcal meningitis and acquired immunodeficiency syndrome (AIDS) is presented . Though cryptococcal infections have been reported from many countries throughout the world, this is the first case reported from Ethiopia in a patient with the acquired immunodeficiency syndrome (AIDS) . The clinical manifestations, diagnosis, and treatment are discussed, with a review of recent literaturePIP: This is the first report from Ethiopia of a case of cryptococcal meningitis in a patient with AIDS . A 20-year-old woman was admitted to Tikur Anbessa Hospital in January 1990 with complaints of generalized pruritic skin lesions of six months, and headache, fever, and poor appetite of three months duration . The headache and low-grade intermittent fever were accompanied by nausea, vomiting, anorexia, and progressive weight loss, without diarrhea . She had had multiple sex partners . Upon admission, after being bedridden for two weeks, she appeared acutely ill and restless . Her temperature was 39.5 degrees Celsius, and she had oral thrush . There was no lymphadenopathy . Widespread, irregular erythematous and whitish macular patches (3 x 5 to 8 x 10 sq . cm in size) with peripheral scaling and tiny vesicles were found on the skin, pubic and perineal regions . She had neck stiffness, but was conscious and well-oriented . Hemoglobin (Hb) was 10.5 g%; the white cell count (WBC) was 3400/cu . mm; the erythrocyte sedimentation rate (ESR) was 92 mm/hr; the platelet count was 175,000/mm; and blood films were negative for hemoparasites . Urinalysis showed 3+ albumin and many pus cells and red cells/HPF . Urine culture was negative, and the VDRL test was nonreactive . Lumbar puncture, which was performed upon arrival, showed clear cerebrospinal fluid (CSF), with normal protein and glucose levels and no cells . CSF culture showed yeast cells, and an India ink preparation was positive for Cryptococcus neoformans . Blood taken for bacterial culture grew yeast cells . Renal and liver function tests, and chest x-rays were normal . A potassium hydroxide (KOH) preparation from a skin snip showed rounded yeast cells . ELISA and Western blot tests were both positive . The patient was given supportive treatment and amphotericin B (0.6 mg/kg daily) . Although the fever decreased, the patient's general condition did not improve . She complained of headache, photophobia, nausea, and vomiting . Lumbar puncture was repeated eight days after the start of treatment; CSF culture and India ink preparations were negative . Urea nitrogen (BUN) repeated two weeks later was normal . Four weeks after admission, the patient suddenly vomited massive amounts of fresh blood and died before transfusion could be given . A discussion follows regarding the clinical manifestations, diagnosis, and treatment of this disease, particularly in AIDS patients, with a review of the literature .

Drugs, 1992 Jul, 44(1), 9 - 35
Systemically administered antifungal agents . A review of their clinical pharmacology and therapeutic applications; Lyman CA et al.; Systemic antifungal agents express great diversity in their pharmacokinetic profiles, mechanisms of action, and toxicities . Understanding the diverse pharmacokinetic properties of systemic antifungals is critical to their appropriate application . Amphotericin B, drug of choice for most invasive mycoses, has unique pharmacokinetic properties, binding initially to serum lipoproteins and redistributing from blood to tissues . Dosing recommendations are based on the specific infection and the status of the host . Lipid formulations of amphotericin B may be able to attenuate some of its toxicities . Flucytosine is a water-soluble, fluorinated pyrimidine that possesses excellent bioavailability . It is administered only in combination with amphotericin B because of frequent development of secondary drug resistance, and is associated with dose-dependent bone marrow suppression . The antifungal azoles are relatively well tolerated, have broad spectrum antifungal activity, and are fungistatic in vitro . Ketoconazole and itraconazole are highly bound to plasma proteins, are extensively metabolised by the liver, and are relatively insoluble in aqueous solution . By comparison, fluconazole is only weakly bound to serum proteins, is relatively stable to metabolic conversion, and is water soluble . Fluconazole penetrates the cerebrospinal fluid well and is approved for primary and suppressive therapy of cryptococcal meningitis in AIDS patients . The echinocandins have a narrow spectrum of antifungal activity, being effective only against Candida spp.

Rev Inst Med Trop Sao Paulo, 1992 Jul-Aug, 34(4), 335 - 40
{The epidemiological characteristics of 105 cases of cryptococcosis diagnosed in the Republic of Argentina between 1981-1990}; Bava AJ et al.; Some epidemiological characteristics of 105 cases of cryptococcosis diagnosed in Argentina, between 1981-1990, were studied . Until 1987, the annual number of cases was 4-8 . It has increased since 1988 by AIDS influence and reached 35 cases in 1990 . The annual number of cases non associated with AIDS has remained in 3-7 cases . The age median of the all patients, AIDS and non AIDS associated cases was 30, 30 and 45 years old, respectively . The 20-39 years old group was the most affected and the age distribution was different in AIDS and non AIDS population . Masculine predominance was more evident in AIDS than in non AIDS associated cases . The predisposing factor was AIDS in 57 patients, another different factor in 20 and unknown in 28 cases . The indirect estimation of the percentage of AIDS cases with cryptococcosis was > or = 6.19% (57 cases in 920 HIV+) during 1981-1990 this period . Cryptococcus neoformans variety neoformans was isolated from 101 cases and the gattii variety (serotype B) from only 4 . The obtained data are similar to those observed in Europe and United States.

Epidemiology, 1992 Jul, 3(4), 310 - 8
An exploratory analysis of survival with AIDS using a nonparametric tree-structured approach; Piette JD et al.; We illustrate an analysis with classification and regression trees applied to survival data . Through this application, we provide a description of the opportunistic diseases and sociodemographic factors that contribute to survival among people with human immunodeficiency virus disease . The analyses are based on 43,795 cases reported to the Centers for Disease Control between January 1, 1984, and December 31, 1987 . We used vital status as of December 31, 1989, to estimate mortality rates . We identified Kaposi's sarcoma and opportunistic diseases causing central nervous system damage (cryptococcosis, primary lymphoma of the brain, cytomegalovirus disease, and progressive multifocal leukoencephalopathy) as important predictors of death . In addition, advanced age at diagnosis (50+), race (white/other), and history of illicit drug use were found to be important determinants . Estimates of the cumulative probability of survival for subgroups of individuals defined by the tree structure illustrate the effect of these determinants on mortality . For the purpose of comparison, two proportional hazards models were also fit to the data using factors identified in the tree structure as the determinants of interest . This application illustrates the utility and limitations of both this new technique and proportional hazards models for epidemiologic research.

Ann N Y Acad Sci, 1992 Jun 16, 653, 257 - 73
Macroepidemiology of the HIVs-AIDS (HAIDS) pandemic . Insufficiently considered zoological and geopolitical aspects; Torres-Anjel MJ; The human immunodeficiency viruses (HIVs)-acquired immunodeficiency syndrome (AIDS) or HAIDS pandemic originated from lentiviruses of nonhuman primates (thus qualifying as a zoonosis) that moved into humans in Africa . The HAIDS patients eventually die of opportunistic infections, all potentially zoonotic . The HAIDS infection remained parochial, first endemically and then epidemically, until the African urbanization that occurred in each of the countries postindependence . The latter included wars and the massive movement of soldiers (virologically naive) from the American continent to Africa and back . The HAIDS viral ecology coincided with African swine fever (ASF) in the Americas . Haiti became the focal point for both infections . Some infected Haitians also became, together with some infected drug addicts in the United States, a source of contaminated human blood for transfusions and production of plasma derivativesPIP: Nonhuman primate lentiviruses are the source of the HIV/AIDS (HAIDS) pandemic among humans . Thus HAIDS constitutes a zoonosis . Opportunistic infections which generally are the immediate cause of death in HAIDS patients tend to be zoonoses . Some of these include tuberculosis, cryptococcosis, cytomegalovirus, toxoplasmosis . Pneumocystis carinii, Listeria monocytogenes, and candidiasis . The HAIDS viral ecology paralleled the intense migration of African swine fever into the Caribbean and the continental Americas . Haitian laborers and prostitutes went to Zaire and later returned . Sexual tourism in Haiti and poor Haitian selling their blood for transfusions and production of plasma derivatives to be marketed to developed countries such as the US and France contributed to the spread of HAIDS from Haiti to developed countries . Thus African swine fever and HAIDS originated in this hemisphere from Haiti after being bought to Haiti from Africa . HAIDS began as an endemic regional disease in Africa then became a regional epidemic disease . After African countries gained independence, urbanization increased in Africa which accounted for the spread of HAIDS in each African country . The US and the USSR played their geopolitical games using and/or resulting in famine, war, and disrupted families on the African continent and elsewhere . Thus husbands from 1 continent were moved to armies and labor camps sometimes on another continent . Prostitution spread tremendously to fulfill women's economic needs and men's sexual needs . HAIDS spread along with these events, e.g . Cuba sent troops to Angola where they were mostly stationed near 2 countries with high HAIDS rates, Zaire and Namibia . These troops often returned to Cuba then returned to Africa . During the 1980s, HAIDS prevalence was 45 times higher among Cuban boat refugees and Marielito Cuban immigrants to the US than that claimed for all of Cuba . In fact, their HAIDS prevalence matched that of Cuba's Caribbean neighbors .

Tidsskr Nor Laegeforen, 1992 Jun 10, 112(15), 1961 - 3
{Fluconazole--a new antifungal agent}; Dobloug JH; Fluconazole (Diflucan) is a new triazole antifungal agent that is effective against a wide range of fungi and has a favourable pharmacokinetic profile . Fluconazole is absorbed well after oral intake independent of food intake . Fluconazole is given once daily, in a dose of 50-400 mg . The dosage is the same for oral and parenteral administration . Tissue penetration is good, as is the concentration in cerebrospinal fluid . Fluconazole should not be given to children under 16 years of age, nor to pregnant or breast-feeding women . In Norway, fluconazole is indicated for treatment of candida vaginitis that is resistant to other treatment, invasive candida infection, candida stomatitis in immunocompromised hosts, and cryptococcal meningitis.

Tidsskr Nor Laegeforen, 1992 Jun 10, 112(15), 1940 - 4
{Systemic mycoses . Epidemiology, clinical aspects, diagnosis}; Dobloug JH; Systemic mycoses are serious, often life-threatening, infections that are encountered with increasing frequency in many countries . These infections are most often seen as a result of advanced medical treatment leading to profoundly immuno-suppressed patients . In Norway, most systemic mycoses are caused by Candida, followed by Aspergillus, Cryptococci and Mucorales . This paper deals with the pathogenetic and immunologic mechanisms underlying these infections . The different agents are described, and the various clinical manifestations . A discussion of the diagnosis of systemic mycoses is followed by some general considerations regarding treatment.

Aust Vet J, 1992 Jun, 69(6), 135 - 9
Cryptococcosis in seven horses; Riley CB et al.; The clinical, radiographic and post-mortem findings in 6 horses with cryptococcal pneumonia and one horse with an abdominal cryptococcal granuloma are described . In pulmonary cryptococcosis, the lesions were either diffuse and multiple, with bilateral lung involvement, or localised mainly to the dorsocaudal region of one lung . The cases of diffuse multiple cryptococcosis were thought to be associated with haematogenous spread of the fungus after gastrointestinal infection and dissemination from regional lymph nodes . The localised form of the disease was thought to have been associated with inhalation of cryptococci . In all cases of pulmonary cryptococcosis, encapsulated yeast-like organisms were demonstrated in Wright's-stained sediment of tracheal washes . In the horse with the abdominal granuloma, cryptococci were present in a fine needle aspirate sample . Isolates of Cryptococcus neoformans var gattii were recovered from 2 of the 5 horses in which cultures were attempted . In addition to a history of previous illness that may have predisposed to infection, most horses in this report had been in areas in which Eucalyptus camaldulensis, or the closely related E rudis, were growing . In humans, an epidemiological relationship between E camaldulensis and infection with C neoformans var gattii has been suggested . Cases of equine cryptococcosis carry a poor prognosis and treatment was not attempted in any of these cases.

Eur J Immunol, 1992 Jun, 22(6), 1447 - 54
Cytokine enhancement of complement-dependent phagocytosis by macrophages: synergy of tumor necrosis factor-alpha and granulocyte-macrophage colony-stimulating factor for phagocytosis of Cryptococcus neoformans; Collins HL et al.; We have examined the regulation of complement dependent phagocytosis by macrophage-activating cytokines . Tumor necrosis factor (TNF)-alpha and granulocyte-macrophage colony-stimulating factor (GM-CSF), but not interferon-gamma, interleukin-4 or macrophage-CSF, stimulated ingestion of the encapsulated fungal pathogen Cryptococcus neoformans by resident peritoneal macrophages in vitro . This was dependent upon opsonization of the yeasts with complement, 72 h of incubation with the cytokines for maximum effect, and the obligate involvement of the macrophage CR3 receptor . TNF-alpha and GM-CSF synergized at low concentrations, resulting in dramatic up-regulation of phagocytosis when compared to either cytokine alone . Supernatants from C . neoformans-specific T cells also increased macrophage phagocytic efficiency . Finally, the administration of neutralizing mAb specific for TNF-alpha and GM-CSF increased mortality in C . neoformans-infected mice, and induced the rapid progression of disease with involvement of the brain and meninges . We conclude that TNF-alpha and GM-CSF are potent regulators of complement-dependent phagocytosis by murine macrophages . Macrophage activation with these two cytokines can completely overcome the anti-phagocytic properties of the virulent yeasts . Our results, therefore, implicate TNF-alpha and GM-CSF as important mediators of resistance to encapsulated pathogens such as C . neoformans where ingestion of the organism is a critical process in host resistance.

Mol Cell Biol, 1992 Jun, 12(6), 2777 - 83
Isolation of telomerelike sequences from Cryptococcus neoformans and their use in high-efficiency transformation; Edman JC; Development of a transformation system for the fungal human pathogen Cryptococcus neoformans is an important prerequisite for the identification of genes involved in virulence . It has previously been reported that low-efficiency transformation can be achieved by using the cloned C . neoformans URA5 gene and ura5 mutants . The introduction of linearized URA5 vectors into C . neoformans resulted in unstable transformants which apparently harbored linear extrachromosomal DNA molecules . In this paper, the nature of these molecules is confirmed to be linear by exonuclease digestion . Recovery of the extrachromosomal DNA in Escherichia coli and sequence analysis demonstrates that repeats characteristic of telomeric DNA have been added to the ends of the introduced DNA . The recovered plasmids are capable of transforming at much higher efficiencies either in the supercoiled state (up to 200 transformants per microgram) or the linear state (up to 90,000 transformants per microgram).

J Exp Med, 1992 Jun 1, 175(6), 1685 - 95
CD4+ T cells cause multinucleated giant cells to form around Cryptococcus neoformans and confine the yeast within the primary site of infection in the respiratory tract; Hill JO; The possible mechanisms by which CD4+ T cells prevent the dissemination of Cryptococcus neoformans from the primary site of infection in the respiratory tract were examined . It was found that even before fungicidal mechanisms are fully induced in the lungs, the host generates a CD4+ T cell-dependent inflammatory response that sequesters yeast within the pulmonary alveoli . This confinement is evident histopathologically and demonstrable objectively as a rapid decline in the ability to dislodge yeast from the lungs by bronchopulmonary lavage . One striking component of this response is the enclosure of cryptococci within multinucleated giant cells in granulomas . Studies in severe combined immunodeficient mice that were engrafted with selected lymphocyte subpopulations show that B cells, and hence anti-Cryptococcus antibodies, are not necessary for the CD4+ T cell-dependent responses that isolate and subsequently destroy this opportunistic pathogen in the lung parenchyma.

J Infect Dis, 1992 Jun, 165(6), 1086 - 93
Antibodies elicited by a Cryptococcus neoformans-tetanus toxoid conjugate vaccine have the same specificity as those elicited in infection; Casadevall A et al.; The antibody responses of BALB/c mice to serotype A Cryptococcus neoformans capsular polysaccharide (CNPS) were compared after cryptococcal infection and immunization with a serotype A glucuronoxylomannan-tetanus toxoid conjugate (GXM-TT) . Infection rarely resulted in a rise of serum antibody titer to CNPS . In contrast, mice immunized with GXM-TT produced serum IgM and IgG to CNPS . Six IgM and one IgG1 monoclonal antibodies (MAbs) were generated from the spleen of one infected mouse . Nine IgM, 1 IgG3, 16 IgG1, and 7 IgA MAbs were generated from the spleen of one GXM-TT-immunized mouse . All MAbs generated from both mice bound to the GXM fraction of the capsular polysaccharide . For some MAbs, de-O-acetylation of serotype A GXM abolished or greatly reduced MAb binding compared with the native GXM . All MAbs reacted with CNPS from C . neoformans serotypes A-D . MAbs generated from the infected mouse competitively inhibited the binding of MAbs generated from the GXM-TT-immunized mouse . These results indicate that some antibodies elicited by infection with C . neoformans or by immunization with GXM-TT bind to the same antigenic determinant in the GXM.

Am J Dermatopathol, 1992 Jun, 14(3), 211 - 5
Palisading granulomas caused by infectious diseases; Su WP et al.; We recently encountered a palisading granuloma in which an infectious cause was not considered until special stains revealed hyphae and tissue culture revealed organisms of phaeohyphomycosis . A review of more than 2,500 cases of various granulomas revealed 11 cases of palisading-type granuloma caused by infection, including phaeohyphomycosis, nontuberculous mycobacteriosis, papulonecrotic tuberculid, tuberculoid syphiloderm, cat-scratch disease, sporotrichosis, cryptococcosis, and coccidioidomycosis . Infectious disease should be considered in the differential diagnosis of palisading granuloma . Special stains for bacteria, fungi, and acid-fast bacilli should be performed in biopsy specimens that have a palisading granuloma pattern with central necrosis, especially in immunosuppressed patients.

J Antibiot (Tokyo), 1992 Jun, 45(6), 861 - 7
Sphingofungins A, B, C, and D; a new family of antifungal agents . I . Fermentation, isolation, and biological activity; VanMiddlesworth F et al.; In screening for antifungal inhibitors from fungi, four related antifungal agents have been isolated from the cultivation of Aspergillus fumigatus ATCC 20857 . These agents were initially produced by the microorganism growing on a solid millet-based medium . A liquid medium containing both glucose and glycerol has also been developed in which these antibiotics are produced in two phases . These novel compounds, sphingofungins A, B, C, and D, show a limited spectrum of antifungal activity but were especially effective against Cryptococcus species.

J Am Soc Nephrol, 1992 Jun, 2(12 Suppl), S264 - 9
Opportunistic fungal and bacterial infection in the renal transplant recipient; Tolkoff-Rubin NE et al.; The risk of opportunistic infection in the renal transplant recipient is determined by the interaction between two factors: the epidemiologic exposures the individual encounters within the community and the hospital and a complex function termed the net state of immunosuppression . There are two general categories of opportunistic fungal infection in this patient population: (1) disseminated primary or reactivation infection with one of the geographically restricted systemic mycoses (histoplasmosis, coccidioidomycosis, blastomycosis, and paracoccidioidomycosis) and (2) opportunistic infection with fungal species that rarely cause invasive infection in the normal host (Aspergillus species, Candida species, Cryptococcus neoformans, and the Mucoraceae), with these last usually being acquired within the hospital environment . Newly available azole compounds, fluconazole and itraconazole, are exciting new alternatives to amphotericin in the treatment of at least some of these infections . The three most important forms of opportunistic bacterial infections are those due to Listeria monocytogenes, Nocardia asteroides, and a variety of mycobacterial species . Clinical diseases with these first two are effectively prevented by low-dose trimethoprim-sulfamethoxazole prophylaxis . There are two cardinal therapeutic rules to be followed by clinicians in dealing with these infections: prevention is better than treatment; when treatment is required, however, the major determinant of the success of therapy is the rapidity with which the diagnosis is made and effective therapy is initiated.

Q J Med, 1992 Jun, 83(302), 473 - 88
A study of neuropathy in HIV infection; Winer JB et al.; A prospective study of possible aetiological factors for neuropathy associated with HIV infection was performed in 80 patients and 28 homosexual controls . At entry to the study twelve patients (15 per cent) had evidence of a generalized neuropathy not due to any other cause and a further three patients developed symptomatic neuropathy during a mean (SD) follow-up of 20 (7.5) months . All but two of these neuropathies were of the distal symmetrical sensory type . Electrophysiology was consistent with an axonal pathology and nerve biopsy confirmed this as the major pathological change . Warming threshold was the diagnostic test most frequently abnormal, sometimes in the absence of other electrophysiological abnormalities . No association was seen with opportunistic infection (cytomegalovirus, herpes simplex, Pneumocystis pneumonia, toxoplasmosis, Cryptococcus infection or tuberculosis) . HIV proviral DNA could not be detected in paraffin sections of peripheral nerve in six patients with neuropathy . The presence of the neuropathy did not show significant correlation with depression of the number of CD4+ T cells in the blood, impaired T cell function tests, or IgG, IgM, or IgA levels . Immune complexes containing C1q, but not those containing IgG, IgM, IgA or C3c, were significantly more common among neuropathic patients (p = 0.01).

J Ethnopharmacol, 1992 Jun, 36(3), 207 - 11
Essential oils and antimicrobial activity of two varieties of Cedronella canariensis (L.) W . et B; Lopez-Garcia RE et al.; The qualitative and quantitative determination of the essential oils of the aerial part of two varieties of Cedronella canariensis (L.) W . et B., namely, C . canariensis var . canariensis and C . canariensis var . anisata have been performed, together with the study of the antimicrobial activity of both oils . The noteworthy inhibition exhibited against Bordetella bronchiseptica and Cryptococcus albidus may justify the popular use of the these plants in the treatment of certain diseases of the respiratory tract.

Antibiot Khimioter, 1992 Jun, 37(6), 7 - 9
{Physiological characteristics of the strains of Cryptococcus deffluens--producers of penicillin acylase}; Shishlova OR et al.; A fermentation medium balanced by the main components was developed for Cryptococcus diffluens strains producing penicillin-V-acylases (PA) . It was shown that the culture needed for production of the enzyme was inductor, which was phenoxyacetic acid (POAA) . Additional introduction of ethanol to the medium provided an increase in production of PA by 36 per cent and the culture growth by 25 per cent . Introduction of one of the following substances to the medium with POAA and ethanol i.e . (CN3COO)2Ca, FeSO4, proline or asparagine provided an additional increase in the production level of PA by 24 to 94 per cent . The use of the medium varieties will permit one to isolate highly productive cells of the culture.

Ugeskr Laeger, 1992 May 11, 154(20), 1419 - 21
{Emphysematous pyelonephritis . A serious complication of diabetes mellitus}; Andersen JB; Pyelonephritis emphysematous (PE) is a life threatening renal infection which is observed practically exclusively as a serious complication of diabetes mellitus . 95% of the 73 cases which have been reviewed were found in diabetic patients . The symptomatology resembles that of severe acute pyelonephritis but the disease differs from this in that, in PE, emphysema develops in the actual renal parenchyma and/or in the perirenal tissues . The most important single factor in the etiology appears to be ischaemia of the tissues which are employed as growth media for the microorganisms involved . Infections with E . coli, Klebsiella pneumoniae, Aerobacter and Proteus are the most commonly found . Isolated cases with Candida and Cryptococcus neoformans have been observed . The mortality in untreated cases of PE is 100% . With medical treatment alone, the mortality decreases to 73% while, when combined medical and surgical intervention is employed, the mortality can be reduced to 30%.

Nihon Kyobu Shikkan Gakkai Zasshi, 1992 May, 30(5), 746 - 55
{Pulmonary lesions of acquired immunodeficiency syndrome--analysis of 24 Japanese autopsy cases with AIDS}; Koike M et al.; The pulmonary lesions were studied in 24 autopsy cases of Japanese patients with AIDS . The major pathological findings were opportunistic infections, which were the major clinical symptoms in some patients . The pathogens identified were as follows; Pneumocystis carinii (PC) in 10, cytomegalovirus (CMV) in 14, atypical mycobacterium in 5, cryptococcus in 2, candida in 2, and nocardia in 1 . PC pneumonia was prominent in 8 cases and was the cause of death . In such patients, the lung were heavy and appeared parenchymatous . Histological examination revealed numerous protozoa in the foamy material in the alveolar spaces, associated with swelling of the alveolar lining cells and edematous thickening of the alveolar septa . In some cases, only hyaline membrane formation was prominent without foamy material in the alveolar spaces . Immunostaining with anti-PC monoclonal antibody or in-situ hybridization with oligopeptide demonstrated pathogens in the hyaline membranes . Many cases with PC pneumonia had concomitant opportunistic infections such as CMV, Herpes simplex virus, and atypical mycobacterium . Extrapulmonary infection of PC was seen in only one case . CMV infection was found in 14 cases; 7 had innumerable inclusion bodies, and in some cases the lesions were most prominent around the bronchioles . Of the 5 cases of atypical mycobacterial infection, 2 were caused by M . kansaii (MK) and 3 by M . avium intracellulare (MAI) . Both lesions of MK infection showed necrosis and cavitation . One of three cases of MAI infection showed cavitation . Around the cavitary lesions, numerous cytomegalic inclusion bodies were identified in the mesenchymal cells, which may have been the cause of necrosis and cavitation of the lesions . MAI infection was systemic and pronounced in the lymph nodes, spleen, and intestinal mucosa . Neoplastic lesions comprised 2 cases of Kaposi's sarcoma and 4 of extranodal non-Hodgkin lymphoma in other organs . Lung involvement was seen in only one case of Kaposi's sarcoma although very small in size . The lesion was situated along the pulmonary vein and appeared hemorrhagic macroscopically . Pulmonary lesions in AIDS are complicated, and many of opportunistic pathogens were identified in single patients.

Arzneimittelforschung, 1992 May, 42(5A), 699 - 705
In vitro activity of sertaconazole; Palacin C et al.; The activity of 7-chloro-3-{1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl) ethoxy-methyl}benzo{b}thiophene (sertaconazole, FI 7045, CAS 99592-32-2), a new topical antifungal, was studied in vitro against several infecting organisms . The results obtained show that sertaconazole is a broad-spectrum antifungal against yeasts (C . albicans, C . tropicalis, C . pseudotropicalis, C . krusei, Trichosporon and Cryptococcus), dermatophytes (Microsporum, Trichophyton and Epidermophyton), opportunistic filamentous fungi (Aspergillus) and Gram-positive bacteria . The MIC (minimum inhibitory concentration) values for the fungistatic activity were between 0.35 and 5.04 micrograms/ml for yeasts and between 0.24 and 2 micrograms/ml for dermatophytes; even partial activities (IC25) against these organisms were obtained at concentrations 10 times lower than those mentioned . At concentrations superior to MIC (MFC between 0.5 and 16 micrograms/ml), sertaconazole exhibited fungicidal activity.

Rev Clin Esp, 1992 May, 190(9), 450 - 4
{Cryptococcosis in AIDS patients: a study of 19 cases}; Gazapo Carretero E et al.; We discuss 19 cases of infection due to Cryptococcus neoformans diagnosed in 438 AIDS patients admitted to our center (4%) . Fourteen of them showed meningitis confirmed by culture of C . neoformans in CSF . Clinical features were rather unspecific and disorders in CSF parameters were non striking . The diagnostic techniques performed with best results were culture of C . neoformans and antigen determination, especially in serum . Survival probability at one year was 75% . Treatment response was good . Treatment with fluocytosine did not seem to provide additional benefits versus amphotericin alone, neither in respect to clinical evolution nor regarding survival probability at one year . Fluconazole has shown effectiveness in maintenance therapy, being not be possible to evaluate it as an acute phase therapy because the low number of cases in which it was studied . It is advisable to follow a suppressive treatment, having found a 10% relapse rate in patients following therapy and a 50% in those who interrupted it.

Int J STD AIDS, 1992 May-Jun, 3(3), 168 - 72
Cryptococcal infection in AIDS; Coker RJ; PIP: Cryptococcus neoformans is an important opportunist pathogen in human immunodeficiency virus (HIV) infection . Cryptococcal meningitis (CM) 3rd after primary HIV neuropathy an Toxoplasma gondii among infectious neurological diseases in AIDS patients . Extrapulmonary infection due to C . neoformans has occurred in up to 13% of patients . 86% of the Cryptococcus spp isolates in the US, Canada, and Japan are serotype A . Thousands of infection due to var neoformans have been reported in AIDS patients but only 3 cases of var gattii . Cryptococcal pneumonia meningitis appears in 63-84% of AIDS patients with symptoms of fever, headache, meningism, and photophobia . 17-37% of AIDS patients with Cm die during therapy, and only 18-30% live over 12 months . Treatment in patients without immunodeficiency deficit is with a combination of .3 mg/kg/day of amphotericin B and 150 mg/kg/day of flucytosine for 4 weeks . A dose of .5-.8 mg/kg/day amphotericin was most effective although renal toxicity occurred in 80% of patients . Fluconazole has been used since 1987: cerebrospinal fluid concentrations reached 60-80% in serum . Treatment in 8 of 14 patients receiving 400 mg/day fluconazole failed while it did not in 6 patients treated with .7 mg/kg/day of amphotericin for 7 days and flucytosine 100 mg/kg/day . 200 mg/bid itraconazole was given to 32 patients with cryptococcosis (24 CM cases and 26 AIDS victims) and 65% of CM patients improved clinically with negative cultures . The relapse of 2 of 106 patients taking 200 mg/day fluconazole and 13 of 77 patients taking 1 mg/kg/week amphotericin B occurred in maintenance therapy . CM was suppressed in 10 of 15 patients with 400 mg/kg itrazonazole . Prophylactic use of azole drugs in AIDS does not protect completely from CM although it reduced systemic fungal infections such as cryptococcosis .

AIDS, 1992 May, 6(5), 467 - 73
The spectrum of clinical and pathological manifestations of AIDS in a consecutive series of autopsied patients in Mexico; Mohar A et al.; OBJECTIVE: Little is known about the clinical profile of AIDS in Latin American populations . This study characterizes the clinical and pathological manifestations of AIDS in a representative series of Mexican AIDS patients at autopsy . DESIGN: The clinical and pathological findings were abstracted retrospectively for a sequential series of autopsied AIDS patients . SETTING: Autopsies were conducted at the four major tertiary level hospitals that serve the majority of AIDS patients in Mexico City . PATIENTS: Subjects included 177 consecutive patients diagnosed with AIDS between March 1984 and January 1989 who subsequently died and were autopsied in the same period in the study hospitals . MAIN OUTCOME MEASURES: Demographic characteristics, including age, gender, residence, socioeconomic status, and risk group; clinical presentation and autopsy findings, including opportunistic infections and malignancies . RESULTS: Sixty per cent of the AIDS patients presented with wasting syndrome . The most common infections were cytomegalovirus (69%), tuberculosis (25%), and Pneumocystis carinii pneumonia (24%) . Central nervous system infections were also common and included toxoplasmosis (19%) and cryptococcoses (10%) . Kaposi's sarcoma was present in 30% of cases and non-Hodgkin's lymphoma in 9% . CONCLUSION: Clinical manifestation, and types and frequency of opportunistic infections in our Mexican AIDS patients were more similar to those seen in AIDS patients in Africa and Haiti than in the United States and Europe . These findings suggest that the AIDS epidemic in Mexico has an 'intermediate' pattern and may be a prototype for Latin American countries.

Klin Monatsbl Augenheilkd, 1992 May, 200(5), 555 - 8
{Ocular complications of AIDS . Diagnostic problems}; Martenet AC; Presentation is made of the ocular complications of AIDS which were observed in the ophthalmologic clinic of the University Hospital in Zurich from 1986 to 1991 . Besides cotton-wool spots, CMV-retinitis is the most frequent and best known infectious complication . In all other infections, diagnosis is most difficult, because it could never be supported by histological examination . Presentation is made of some cases of acute retinal necrosis, toxoplasmosis, cryptococcosis, candida, and of some cases of uveitis with unknown etiology . Furthermore we present one intraocular non-Hodgkin lymphoma, some suspicions of Kaposi's sarcoma and some neurologic disturbances of central origin.

Clin Infect Dis, 1992 May, 14(5), 1142 - 4
Pancoast's syndrome due to pulmonary infection with Cryptococcus neoformans variety gattii; Mitchell DH et al.; Immunocompetent hosts usually do not require antifungal therapy for pulmonary cryptococcosis . We present a case of right lung mass and Pancoast's syndrome due to locally invasive Cryptococcus neoformans variety gattii in a normal host . Lobectomy followed by therapy with amphotericin B and flucytosine was curative.

Clin Infect Dis, 1992 May, 14(5), 1069 - 73
Cryptococcal endophthalmitis: case report and review; Crump JR et al.; Cryptococcus neoformans is an opportunistic fungus with a predilection for infecting the meninges . Ocular sequelae of cryptococcal infections of the CNS usually include cranial nerve palsies or papilledema secondary to increased intracranial pressure . Intraocular cryptococcosis occurs less frequently, and over the last 23 years, only 27 cases have been reported, including the case presented here . Intraocular infection was most often manifested by chorioretinal lesions and vitritis . Underlying diseases were detected in only 11 (41%) of the 27 patients . Of note, ocular lesions preceded symptomatic meningitis in six (27%) of 22 patients with CNS involvement . For seven patients, the diagnosis was made by histologic examination of specimens of aqueous or vitreous humor; for another eight patients, the diagnosis was made after enucleation or at autopsy . Ocular involvement frequently led to severe visual loss; return of vision to normal was unusual . Early recognition and treatment may improve outcome for these patients.

Ophthalmology, 1992 May, 99(5), 813 - 6
Cryptococcosis of the anterior segment in acquired immune deficiency syndrome; Charles NC et al.; Cryptococcosis is a rare form of human ocular infection, usually occurring in immunocompromised patients . Unilateral or bilateral posterior segment involvement is the rule . The authors describe a unique case of intraocular cryptococcosis presenting as an iris inflammatory mass in a patient with acquired immune deficiency syndrome . Diagnosis was established by anterior chamber paracentesis and confirmed by histopathologic examination of the enucleated eye.

Am Rev Respir Dis, 1992 May, 145(5), 1226 - 9
Detection of cryptococcal antigen in bronchoalveolar lavage fluid: a prospective study of diagnostic utility; Baughman RP et al.; Cryptococcal pneumonia is associated with significant morbidity and mortality in immunocompromised patients . We examined the utility of screening bronchoalveolar lavage (BAL) fluid for cryptococcal antigen . In a pilot study, we found that cryptococcal antigen was always positive in unprocessed BAL specimens of seven patients with cryptococcal pneumonia and negative in 44 patients with other granulomatous diseases who acted as the control subjects . A prospective study was done of 220 immunocompromised patients (188 with human immunodeficiency virus infection, 32 with other causes of immunosuppression) undergoing BAL for fever and pulmonary symptoms . The eventual diagnosis of cryptococcal pneumonia was made in eight patients . All eight patients had a cryptococcal antigen titer greater than or equal to 1:8 . There were four patients without cryptococcal pneumonia who had cryptococcal antigen titers of 1:8, there were none with higher titers . For a titer of cryptococcal antigen titer of greater than or equal to 1:8, there was 100% sensitivity, 98% specificity, a positive predictive value of 67%, and a negative predictive value of 100% . The measurement of cryptococcal antigen in the BAL can be a rapid, simple way to make a diagnosis of cryptococcal pneumonia in immunosuppressed patients with pneumonia.

Am J Clin Pathol, 1992 May, 97(5), 663 - 4
Coulter counter identifies Cryptococcus neoformans as leukocytes . A case of pseudopleocytosis; Berger SA et al.; Cerebrospinal fluid from a 42-year-old man with acquired immune deficiency syndrome was processed in a Coulter S-plus counter and found to contain "4.8 x 10(9) leukocytes/L:56.1% granulocytes and 37.7% lymphocytes." Direct examination of the same specimen in a counting chamber revealed that the leukocytes were cells of Cryptococcus neoformans . Coulter analysis of cerebrospinal fluid may be inappropriate, particularly when yeast infection is a probable diagnosis.

Ann Thorac Surg, 1992 May, 53(5), 892 - 3
Primary pulmonary cryptococcosis presenting as a superior sulcus tumor; Ziomek S et al.; A patient underwent resection of a superior sulcus tumor after an extensive workup was nondiagnostic . Postoperatively, primary pulmonary cryptococcosis was diagnosed . Management of this patient is presented along with a review of the literature.

J Infect Dis, 1992 May, 165(5), 960 - 3
Cryptococcal meningitis: outcome in patients with AIDS and patients with neoplastic disease; White M et al.; A retrospective analysis of 41 patients with cryptococcal meningitis and AIDS or neoplastic disease was done . Patients with AIDS were younger and predominantly male; they had a shorter duration of prior illness, higher initial serum cryptococcal antigen titers, and lower initial cerebrospinal fluid white blood cell counts than those with neoplastic disease . The median overall survival for patients with AIDS was 9 months compared with 2 months for those with neoplastic disease (P = .004) . Seventy-eight percent of patients with AIDS and 43% of those with neoplastic disease were cured or improved 6 months after diagnosis (P = .039) . Toxicity from amphotericin B and flucytosine was similar for both groups . One patient with AIDS relapsed . Multivariate predictors of survival included headache (P = .007) and an AIDS diagnosis (P = .009) . Examination of outcomes for other opportunistic infections associated with AIDS and other immunosuppressive illness may distinguish prognostic features for different patient populations.

Infect Immun, 1992 May, 60(5), 1869 - 74
Virulence, serotype, and molecular characteristics of environmental strains of Cryptococcus neoformans var . gattii; Kwon-Chung KJ et al.; Four strains of Cryptococcus neoformans var . gattii originating from Eucalyptus camaldulensis, three from Australia and one from San Francisco, were tested for their serotype, virulence for mice, and a number of genetic and molecular characteristics . All were found to be serotype B and showed significantly higher virulence for mice than did the type strains of C . neoformans var . gattii and Filobasidiella neoformans var . bacillispora, which were obtained from human cryptococcosis cases . Electrophoretic karyotypes of the strains from Australia were identical, although they were collected from sites at least 15 to 500 km apart . The electrophoretic karyotype of the strain from San Francisco was the same as that of the Australian isolates except for the mobility of one chromosome . On the contrary, no two isolates of serotype B (of a total of 11) from clinical sources were the same, regardless of their geographic origin . Furthermore, none of the clinical isolates showed a chromosomal banding pattern identical to that of Eucalyptus-originated strains . The Eucalyptus-originated strains failed to form dikaryons when crossed with the tester strains of the two varieties of F . neoformans . Hybridization analysis with a nucleic acid probe (AccuProbe C . neoformans Culture Confirmation Test; Gen-Probe Inc., San Diego, Calif.), however, showed signals of equal intensity for clinical strains and the Eucalyptus-originated strains . Various fungi phylogenetically related to C . neoformans, including a phenol oxidase-positive strain of Cryptococcus laurentii obtained from E . camaldulensis, were negative in the nucleic acid hybridization test . These observations confirm that, in spite of karyotypic differences and the lack of dikaryon formation with the tester strains of F . neoformans, Eucalyptus-originated C . neoformans var . gattii is the same organism as those isolated from cases of human infection . Furthermore, the C . neoformans culture confirmation test using a commercial nucleic acid probe is specific for C . neoformans.

Tohoku J Exp Med, 1992 May, 167(1), 13 - 8
Prevalence of HTLV-I antibody in pulmonary cryptococcosis; Kohno S et al.; A retrospective study was done to determine the prevalence of anti-HTLV-I antibodies in patients with pulmonary cryptococcosis . None of the 19 patients with pulmonary cryptococcosis had underlying immunodeficiency . Anti-HTLV-I antibody was present in 6 (32%) of 19 patients with pulmonary cryptococcosis, a significantly higher prevalence than found in patients with bronchial asthma (4 (7%) of 58) (p less than 0.01, chi-square test) . No statistical difference was noted when anti-HTLV-I antibody seropositivity was compared to that of patients with pulmonary tuberculosis (16% (17/105)), lung cancer (17% (22/129)) and pneumonia (9% (6/64)) . A reduced cellular immunity as shown by lymphopenia, the CD4/CD8 ratio, and purified protein derivative skin test was found in only 1 (5%) of 19, 2 (12%) of 17, and 6 (33%) of 18 patients, respectively . These results do not explain the susceptibility to pulmonary cryptococcosis in HTLV-I carriers . This is the first report of high prevalence of pulmonary cryptococcosis in HTLV-I carriers and it raises the question whether HTLV-I carriers are more susceptible to opportunistic infections and other malignancies probably due to subtle immunological abnormalities.

Xenobiotica, 1992 May, 22(5), 569 - 77
The metabolism of muzigadial by microorganisms; Jurgens TM et al.; 1 . A total of 114 microorganisms were evaluated for their ability to metabolize the antifungal drimane sesquiterpene, muzigadial . 2 . Cryptococcus neoformans was found to convert muzigadial to one major metabolite, identified as a hemiacetal . 3 . Streptomyces platensis produced three metabolites: the hemiacetal, its corresponding lactone, and the epoxide of the hemiacetal . 4 . Streptomyces spectabilis produced the hemiacetal as well as the epoxy hemiacetal . 5 . The proposed structures of all of the metabolites were based on comparisons of the spectroscopic data (1H- and 13C-n.m.r . spectra and mass spectra) between the metabolites and the parent compound . 6 . Antimicrobial evaluation of the microbial metabolites indicate that metabolism decreases antifungal activity.

Eur J Epidemiol, 1992 May, 8(3), 377 - 82
Immunohistologic diagnosis of systemic mycoses: an update; Kaufman L; Fluorescent antibody, immunoperoxidase and gold-silver staining methods for the rapid and accurate diagnosis of systemic mycotic infections are currently performed in a few specialized laboratories . These methods have proved applicable to formalin-fixed, paraffin-embedded tissues, and are reliable for identifying therein antigens of infectious dimorphic, monomorphic filamentous, and yeast-like fungal pathogens, i.e., Aspergillus spp., Blastomyces dermatitidis, Candida spp., Coccidioides immitis, Cryptococcus neoformans, Fusarium spp., Histoplasma capsulatum, Paracoccidioides brasiliensis, Pseudallescheria boydii, and Sporothrix schenckii . Most of the available reagents are derived from multiple adsorbed polyclonal antisera . However, problems occur in the production of uniform and standardized species- or genus- specific antibodies . Monoclonal antibodies, although promising, have to date not eliminated these problems . Immunohistologic methods will become more routinely used in clinical laboratories as these problems are resolved and more sensitive and specific reagents become commercially available.

Eur J Epidemiol, 1992 May, 8(3), 321 - 5
The ecology of Cryptococcus neoformans; Ellis D et al.; Environmental isolations have established that Cryptococcus neoformans var . gattii serotype B appears to have a specific ecological association with Eucalyptus camaldulensis . The global distribution of the tree appears to correspond to the epidemiologic distribution of cryptococcosis caused by C . neoformans var . gattii . The epidemiology of cryptococcosis can primarily be explained by exposure to an infective aerosolized inoculum, such as basidiospores released from specific host plants and/or desiccated blastoconidia (yeast cells) disseminated from accumulations of dried pigeon dung . The ecology of C . neoformans still remains largely unresolved, studies on the host-parasite interaction between serotype B and E . camaldulensis are still in progress, and extensive environmental searches are now underway to determine the natural habitats of serotypes A, C and D.

J Clin Microbiol, 1992 May, 30(5), 1094 - 7
Use of a dispersed repetitive DNA element to distinguish clinical isolates of Cryptococcus neoformans; Spitzer ED et al.; We isolated a recombinant phage from a Cryptococcus neoformans genomic library that contains a member of a dispersed family of repetitive DNA elements . This clone, CNRE-1, hybridized to at least seven chromosomes in C . neoformans on the basis of pulsed-field gel analysis . Hybridization of CNRE-1 to restriction digests of genomic DNA confirmed that there are multiple copies of this element and that restriction fragment length polymorphisms are present in strains from different serotypes of C . neoformans . The utility of this probe as an epidemiologic marker was determined by testing cryptococcal isolates from a single hospital . Five isolates from four patients were closely related to a serotype A reference strain, whereas five other isolates from four additional patients exhibited distinct patterns . In two patients, the isolates obtained during recurrent cryptococcal infections were identical to the original isolates.

J Clin Microbiol, 1992 May, 30(5), 1080 - 4
Extensive allelic variation in Cryptococcus neoformans; Casadevall A et al.; The orotidine monophosphate pyrophosphorylase (OMPPase) gene locus of the DNA of 13 Cryptococcus neoformans var . neoformans strains, including 10 recent clinical isolates, was studied by using restriction fragment length polymorphisms and nucleotide sequence analysis . The OMPPase locus (URA5) is highly polymorphic, and at least six alleles were identified . The nucleotide sequences of some alleles differed by up to 5% . The majority of the nucleotide polymorphisms in the protein-coding region occurred at the third codon position and were silent . The low frequency of replacement nucleotide substitutions relative to silent nucleotide substitutions implied that there is strong selection against amino acid changes in OMPPase . The allelic variation suggested that there is extensive genomic diversity among C . neoformans clinical isolates from one geographic area . The various alleles are potentially useful markers in the study of the population structure, epidemiology, and pathogenesis of C . neoformans strains.

Eur J Epidemiol, 1992 May, 8(3), 422 - 6
Comparative study of six antifungal treatments in an experimental model of murine cryptococcosis; Bava AJ et al.; A comparative study, using 5 antifungal drugs for the treatment of an experimental model of murine cryptococcosis, was carried out . One hundred and eighty Balb C mice, divided in 18 groups of 10 animals each, were intraperitoneally inoculated with 10(7) cells of Cryptococcus neoformans var . neoformans . Twelve groups were treated with different schedules beginning 5 days after inoculation, for 2 or 4 weeks . The treatments were the following: amphotericin B (6 mg/kg/every other day, intraperitoneally); 5-fluorocytosine (300 mg/kg/day, by gavage); amphotericin B (6 mg/kg/every other day, intraperitoneally) in association with 5-fluorocytosine (300 mg/kg/day, by gavage); fluconazole, itraconazole and Sch 39.304 (all at the daily dose of 16 mg/kg, by gavage) . The six remaining groups were used as controls and received the solvent for the drugs . The evaluation of the efficacy of the different treatments was based on: survival time; macroscopy of brain, lungs, liver and spleen at autopsies; presence of encapsulated yeasts in microscopic examination of wet preparations of these organs; and cultures of a concentrated suspension of brain and lungs . In the animals treated for 2 weeks, the combination of amphotericin B + 5-fluorocytosine was the most useful; it negativized the micro and macroscopic findings as well as 90% of the cultures, and prolonged the survival time up to 60 days . Sixty per cent of the mice which received amphotericin B exhibited the same survival time and macroscopic findings as those treated with the association of amphotericin B + 5-fluorocytosine . Among the azolic compounds, Sch 39.304 proved to be the most effective in the prolongation of survival time.(ABSTRACT TRUNCATED AT 250 WORDS)

Nihon Kyobu Shikkan Gakkai Zasshi, 1992 May, 30(5), 756 - 62
{Pulmonary complications in patients with adult T-cell leukemia}; Tashiro T; In order to investigate the character of pulmonary complications in patients with adult T-cell leukemia (ATL), a pathological and bacteriological study was performed in 92 autopsy cases with hematologic malignancies including 17 cases of ATL and 103 autopsy cases with solid malignancies from 1981 to 1990 . Among 17 cases with ATL, pulmonary complications were seen in 16 cases (94.1%); pulmonary infection in 14 (82.3%), leukemic cell pulmonary infiltration in 9 (52.9%), pulmonary hemorrhage in 5 (29.4%), pulmonary alveolar calcinosis in 2 (11.8%), and idiopathic interstitial pneumonia in 2 (11.8%) . The causative microorganisms were virus in 10; 9 of which were cytomegalovirus, followed by bacteria infection in 4 cases, mainly pseudomonas aeruginosa, and fungal infection in 3, mainly cryptococcus . pneumocystic carinii and mycobacterium tuberculosis were not detected . It is suggested that patients with ATL are severely compromised with chiefly cellular immunodeficiency, and administration of sulfamethoxazole-trimethoprim and isoniazid is very effective in prevention of pneumocystis carinii pneumonia and pulmonary tuberculosis.

Carbohydr Res, 1992 Apr 10, 228(1), 47 - 64
Positional isomers of thioxylobiose, their synthesis and inducing ability for D-xylan-degrading enzymes in the yeast Cryptococcus albidus; Defaye J et al.; Isomeric S-linked 2-thioxylobiose 10, 3-thioxylobiose 17, and 4-thioxylobiose 19 were conveniently prepared by SN2 displacement of suitable triflylglycoses with the sodium salt of 2,3,4-tri-O-acetyl-1-thio-beta-D-glucopyranose, either in N,N-dimethylformamide, or in oxolan in the presence of a sodium complexing agent . Allyl 3,5-O-isopropylidene-2-O-trifluoromethanesulfonyl-beta-D-lyxofu ranoside was a convenient electrophilic precursor for 10, which was smoothly obtained after a short sequence of deprotection involving conversion to the 1-propenyl glycoside . 1,2:5,6-Di-O-isopropylidene-3-O-trifluoromethylsulfonyl-alpha-D-++ +allofuranose and 1,2,3-tri-O-benzoyl-4-O-trifluoromethylsulfonyl-beta-L-arabinop yranose were the respective precursors for 17 and 19 . 4-Thioxylobiose has a highly stimulatory effect on the synthesis of enzymes of the xylanolytic system in the yeast Cryptococcus albidus when applied to the cells in the presence of the natural disaccharide inducer (1----4)-beta-D-xylobiose.

J Otolaryngol, 1992 Apr, 21(2), 92 - 4
Fluconazole: a new option in the treatment of Candida mucositis and esophageal candidiasis; Garber GE; Fluconazole is a new triazole antifungal agent with good activity against Candida and cryptococcal meningitis . It is well-tolerated and effective in immunosuppressed patients with oral-pharyngeal candidiasis . This review outlines the characteristics of fluconazole and discusses its role among the class of antifungal agents.

J Clin Microbiol, 1992 Apr, 30(4), 925 - 30
Development of DNA probes for early diagnosis and epidemiological study of cryptococcosis in AIDS patients; Polacheck I et al.; We report the isolation of middle-repetitive DNA sequences from Cryptococcus neoformans that are species and variety specific . These probes were used for assessing strain relatedness among cryptococcal isolates from patients with and without AIDS who were from Zaire and the United States . Five distinct hybridization patterns were observed for the 60 isolates examined, regardless of the restriction enzyme used for digestion . The most common pattern among the isolates from the patients without AIDS was also the most common among the isolates from the patients with AIDS who were from the United States and was the only pattern observed for all isolates tested from patients with AIDS who were from Zaire . On the basis of the high specificity and sensitivity of the signals observed by hybridization, we suggest that these sequences provide a means for both biotyping and early diagnosis of C . neoformans.

J Clin Microbiol, 1992 Apr, 30(4), 894 - 900
Isolation and characterization of a species-specific DNA fragment for detection of Candida albicans by polymerase chain reaction; Miyakawa Y et al.; A 2-kbp DNA fragment, EO3, that was present in multiple copies in the Candida albicans genome was isolated for use in developing a detection method for C . albicans by polymerase chain reaction (PCR) . Dot blot hybridization revealed that EO3 was specific for the 40 isolates of C . albicans serotypes A and B used . Using a set of primers (20-mer each) derived from the nucleotide sequence of EO3, we performed specific amplification of a 1.8-kbp DNA fragment within EO3 by PCR . All 40 isolates belonging to C . albicans serotypes A and B contained amplifiable 1.8-bkp fragments, although the DNA of the amplified products exhibited small variations in size, yielding three different fragment groups . Southern blot hybridization probed with EO3 showed that these 1.8-kbp fragments were derived from the EO3 region . Conversely, the 1.8-kbp fragment was not amplified from 38 isolates belonging to seven other medically important Candida species or from isolates of Cryptococcus neoformans, Saccharomyces cerevisiae, various bacteria, and a human cell line . The detection limit of the PCR assay for C . albicans with the EO3 fragment was shown to be approximately 2 to 10 cells and 100 cells in saline and human urine, respectively, by ethidium bromide staining and 2 and 10 cells, respectively, by Southern blot analysis . In addition, EO3 was assumed to originate from mitochondrial DNA on the basis of the results of its characterizations . These results indicate that the PCR system using the 1.8-kbp fragment as a target is a reliable method for identifying C . albicans isolates, thereby suggesting its potentials for specific and sensitive detection of C . albicans in samples from patients with candidiasis.

J Clin Microbiol, 1992 Apr, 30(4), 1000 - 4
Viability of fungal cultures maintained at -70 degrees C; Pasarell L et al.; One thousand four hundred forty-seven clinical and environmental isolates of molds, yeasts, aerobic actinomycetes, and algae belonging to 164 genera (382 taxa) maintained on potato dextrose agar at -70 degrees C for periods ranging from 6 months to 13 years were subcultured and then incubated at 25 degrees C to determine their viabilities . Thirty-three isolates, Alternaria alternata (n = 1), Apophysomyces elegans (n = 1), Bipolaris spicifera (n = 1), Blastomyces dermatitidis (n = 4), Cokeromyces recurvatus (n = 1), Coremiella cubispora (n = 1), Cryptococcus ater (n = 1), Curvularia sp . (n = 1), Exserohilum monoceras (n = 1), Exserohilum pedicillatum (n = 1), Exserohilum rostratum (n = 1), Filobasidium floriforme (n = 1), Madurella mycetomatis (n = 1), Oedocephalum spp . (n = 2), Penicillium marneffei (n = 1), Pseudomicrodochium spp . (n = 4), Saksenaea vasiformis (n = 1), Sporothrix sp . (n = 1), and Mycelia Sterilia (n = 8), did not grow after repeated attempts at subculturing . Neither time in storage nor taxonomic classification was associated with a lack of viability . Storage at low temperature for either short or long periods of time is an excellent method for maintaining most medically important fungi.

Postgrad Med, 1992 Apr, 91(5), 349 - 50, 353-4, 357-60 passim
Orofacial fungal infections . Nine pathogens that may invade during chemotherapy; Dreizen S et al.; Immunosuppression due to antineoplastic drugs or malignant tumor leaves patients extremely vulnerable to infection . Opportunistic fungi that rarely infect healthy persons can have very severe consequences in these patients . Candida albicans is the pathogen found most often, but several other Candida species may cause infection as well . Aspergillosis is the second most frequently seen fungal infection of the face and mouth in patients receiving chemotherapy . Less commonly seen but equally dangerous are infections with Torulopsis glabrata, Mucor, Absidia, Rhizopus oryzae, Histoplasma capsulatum, Cryptococcus neoformans, Coccidioides immitis, Fusarium species, and Trichosporon cutaneum . Restoration of impaired host defenses and use of nystatin (Mycostatin, Nilstat, O-V Statin), clotrimazole (Mycelex), amphotericin B (Fungizone Intravenous), and flucytosine (Ancobon) when appropriate are methods of control.

Chest, 1992 Apr, 101(4), 1044 - 9
A raised level of soluble CD8 in bronchoalveolar lavage fluid in summer-type hypersensitivity pneumonitis in Japan; Hamagami S et al.; We used ELISA to measure soluble CD8 (sCD8) in the bronchoalveolar lavage fluid (BALF) and serum of patients with summer-type hypersensitivity pneumonitis (HP) . The sCD8 levels in BALF were significantly higher in the patients with summer-type HP, surpassing those found in sarcoidosis and the other pulmonary diseases studied; however, the sCD8 levels in the serum of patients with summer-type HP did not differ from the levels of the healthy controls . The numbers of CD8+ T cells were increased in the BALF of the patients with summer-type HP, and there was a correlation between the sCD8 levels and the concentrations of CD8+ T cells . Gel filtration and polyacrylamide gel electrophoresis of the fluid revealed that the anti-CD8 monoclonal antibody-reactive components in the BALF of patients with pneumonitis corresponded to a protein with a molecular weight of between 52 and 54 kDa . Soluble CD8-rich fraction purified from the BALF of patients with summer-type HP augmented in vitro lymphocytes' proliferative responses stimulated with Cryptococcus neoformans, one of the causative agents for summer-type HP . Our result suggests that soluble CD8 in the BALF may play an important role in the pathogenesis of summer-type HP.

Cesk Epidemiol Mikrobiol Imunol, 1992 Apr, 41(1), 45 - 63
{Mycotic diseases in patients with AIDS}; Tomsikova A; The author analyzes factors influencing the occurrence of mycoses in AIDS-patients with different stages of the disease . The clinical picture, the diagnosis and sources of common as well as uncommon mycoses accompanying AIDS are given in detail . Candidosis, cryptococcosis, histoplasmosis and dermatomycosis complicate AIDS frequently most . The course of all mycoses in AIDS patients is quite different from the course of the same mycoses complicating other diseases.

Oncology (Huntingt), 1992 Apr, 6(4), 81 - 92; discussion 97-100
Current approaches to the management of fungal infections in cancer patients: Part 1; Francis P et al.; Fungal infections in the immunocompromised cancer patient may threaten survival and represent a major therapeutic challenge . Granulocytopenia, especially, increases the risk of infection with the two most common fungal species, Candida and Aspergillus . In cancer patients, mucocutaneous disruptions due to administration of chemotherapeutic agents and use of IV lines, Hickman catheters, and nasogastric tubes provide portals of entry for Candida species . Although cryptococcosis, histoplasmosis, and coccidioidomycosis have gained recent attention because of their increasing prevalence in patients with AIDS, these infections are also seen in cancer patients, especially those receiving corticosteroids . In cancer patients, candidiasis can range from asymptomatic oral thrush to life-threatening candidemia . Although amphotericin B remains a mainstay of treatment, therapeutic and preventive approaches with newer agents such as flucytosine and fluconazole may improve prognosis.

Cutis, 1992 Apr, 49(4), 260 - 4
Coexistent oral cryptococcosis and Kaposi's sarcoma in acquired immunodeficiency syndrome; Kuruvilla A et al.; As experience with the acquired immunodeficiency syndrome has grown during the last decade, it has become important to recognize interactions between the opportunistic infections and malignancies that complicate the course of patients with acquired immunodeficiency syndrome . Our recent experience as described in this paper reveals that Kaposi's sarcoma and cryptococcal infection can associate in such a manner . The first reported case of oral Cryptococcus neoformans infection within a Kaposi's sarcoma lesion in a patient with acquired immunodeficiency syndrome is described . Based on the clinical course of this patient, it is an important consideration that the sarcoma may have harbored and even protected the fungus during systemic amphotericin B therapy.

Ann Ital Med Int, 1992 Apr-Jun, 7(2), 111 - 3
{Cryptococcosis in a female patient with angioimmunoblastic lymphadenopathy and dysproteinemia}; Ghezzo F et al.; A case of a 72-year-old woman affected by angioimmunoblastic lymphadenopathy with dysproteinemia is described . She was admitted to the hospital for serious cutaneous lesions and dementia . The patient had been treated with corticosteroids for the previous two years . Cryptococcosis was diagnosed by cutaneous biopsy . Antimycotic therapy together with corticosteroid withdrawal cured the cutaneous lesions and improved her psychiatric symptoms.

J Assoc Physicians India, 1992 Apr, 40(4), 267 - 8
Efficacy of oral fluconazole in Cryptococcus neoformans infection; Agarwal A et al.; We report a renal allograft recipient who developed disseminated cryptococcosis, which was treated effectively, with oral fluconazole, a new triazole antifungal agent . The patient is doing well on maintenance therapy with fluconazole and immunosuppressive agents.

Med Trop (Mars), 1992 Apr-Jun, 52(2), 179 - 81
{Simultaneous association of tubercular meningitis and cryptococcal meningitis in an African with human immunodeficiency virus HIV positive serology . University Hospital Center of Bujumbura,Burundi}; Niyongabo T et al.; The authors report a connection between a meningitis tuberculosis and a meningoencephalitis with cryptococcus in the case of an african VIH+ . The diagnostic of a meningitis tuberculosis was retained on an indirect arguments, this of meningoencephalitis of direct arguments (antigen cryptococcus, cultivation on Sabouraud environment) . The pulmonary tuberculosis and/or extrapulmonary tuberculosis is current in Central Africa during HIV infection, as well as the crytococcosis during AIDS . But, any observation on neuromeningitis strike of those two infections have been reported up to now.

Baillieres Clin Neurol, 1992 Apr, 1(1), 175 - 209
Other neurological diseases in HIV-1 infection: clinical aspects; Guiloff RJ et al.; HIV-1-related neurological diseases, excluding opportunistic infections and HIV encephalitis, are considered here . Most occur in severely immunosuppressed patients, with CD4 counts of under 200 x 10(6) l-1 . Primary brain lymphoma and metastases from systemic non-Hodgkin's lymphoma, the second commonest cause of cerebral mass lesions in AIDS, are usually aggressive B cell tumours . Their poor median survival after treatment, compared with that of lymphomas in non-AIDS patients, seems related to systemic complications, particularly opportunistic infections . Kaposi's sarcoma produces neurological symptoms exceptionally . Cerebral infarction is often unrecognized clinically but large vessel arteritic occlusions may occur . Intracranial haemorrhages occur mostly in thrombocytopenic patients . Seizures are frequently referred to the neurologist; investigation may lead to a diagnosis of AIDS . Nearly 50% of patients with seizures have cerebral toxoplasmosis or cryptococcal meningitis; HIV-1 encephalitis is presumed to be the cause in 30% . A subacute or chronic vacuolar myelopathy with pyramidal and posterior column signs is the commonest form of spinal cord involvement in AIDS; its cause remains unknown . Peripheral nerve syndromes occur at all stages of HIV-1 infection . Distal symmetrical peripheral neuropathies are the most frequent, particularly a painful form with axonal atrophy, associated with CMV infection, and seen during ARC or AIDS . Mononeuritis multiplex due to vasculitis, CMV, or lymphoma and a serious lumbosacral polyradiculopathy due to CMV are infrequent . The commonest myopathy is due to zidovudine (AZT); it usually responds to drug withdrawal . The nature, prognosis and optimal management of most other myopathies is yet to be determined.

Baillieres Clin Neurol, 1992 Apr, 1(1), 103 - 54
Central nervous system opportunistic infections in HIV disease: clinical aspects; Guiloff RJ et al.; Nervous system opportunistic infections are seen in about one fifth of AIDS cases and account for over 40% of the patients with neurological manifestations . Serious infections are seen in severely immunosuppressed patients, usually with CD4 counts of 200 ml-1 or less . The commonest is CMV, which can produce acute encephalitis, sometimes with focal hemisphere or brain-stem signs, dementia, retinitis, optic neuritis and an ascending radiculomyeloencephalitis . Cryptococcal meningitis is the most frequent fungal disease; a high degree of clinical suspicion is required in patients with fever, malaise, headache or seizures . Only CSF cultures are always positive; both serum and CSF cryptococcal antigen tests are highly sensitive and specific . Treatment with amphotericin B and flucytosine is successful in at least 70% of first episodes but side-effects are common . Without maintenance therapy 50% of patients relapse; fluconazole is recommended . Cerebral toxoplasmosis can present with focal cerebral or spinal cord signs but also as a diffuse encephalopathy; negative T . gondii serology is exceptional but positive serum titres are usually unhelpful . Treatment with sulfadiazine, pyrimethamine and folinic acid achieves good results in 90% of the first episodes, but side-effects are common . Appearances on CT scan or MRI may take several weeks to improve . The value of an empirical approach to treatment is well-established; an initial cerebral biopsy is difficult to justify . Without maintenance therapy a relapse rate of 50% can be expected; therapy with sulfadiazine and pyrimethamine may also prevent pneumocystosis . HIV disease appears to increase the likelihood of neurosyphilis, and the risk of relapse after conventional penicillin doses, in patients with syphilis; at least 3-4 weeks of appropriate therapy are recommended . A number of other diseases caused by viruses, fungi, bacteria and parasites are less common; these include progressive multifocal leukoencephalopathy, herpes simplex and zoster infections and tuberculosis.

G E N, 1992 Apr-Jun, 46(2), 105 - 12
{A morphological study of the liver in the acquired immunodeficiency syndrome . An analysis of 69 cases}; Ruiz ME et al.; The morphologic findings in the liver of 69 autopsy cases with had died of AIDS are presented . The morphologic changes were represented by the presence of opportunistic germs (Histoplasma capsulatum, Mycobacteria, Cryptococcus neoformans and CMV) . Other alterations found were fatty changes, portal fibrosis, dilated and congested sinusoids . We did not find Kaposi's sarcoma in the liver and only one case of lymphoblastic lymphoma was seen observed.

Rev Soc Bras Med Trop, 1992 Apr-Jun, 25(2), 95 - 9
{The neuropathological findings in the acquired immunodeficiency syndrome (AIDS): a review of 138 cases}; Wainstein MV et al.; This is an autopsy study performed in a retrospective fashion to determine the incidence of diseases that could affect the central nervous system in AIDS . For this purpose, 138 autopsies of patients with AIDS performed at the "Hospital de Clinicas de Porto Alegre", Brazil, between January/85 and December/90 were studied . All the brains were evaluated macroscopically and microscopically mainly through hematoxylin-eosin staining and if necessary special techniques like PAS, Grocott, Giemsa and Ziehl-Nielsen were done . Results have revealed 29 (21%) cases with cerebral toxoplasmosis; cryptococcosis in 17 (12%); tuberculosis in two (1%) and one case (0.7%) of candidiasis . Besides these inflammatory lesions, 15 (10%) presented vascular lesion; 8 (6%) had gliosis and 7 (5%) cases had suggestive findings of HIV encephalopathy . We can conclude that the CNS is a important target affected by AIDS and that cerebral toxoplasmosis is the principal disease in the CNS in AIDS patients.

N Engl J Med, 1992 Mar 19, 326(12), 793 - 8
A controlled trial of fluconazole or amphotericin B to prevent relapse of cryptococcal meningitis in patients with the acquired immunodeficiency syndrome . The NIAID AIDS Clinical Trials Group and Mycoses Study Group; Powderly WG et al.; BACKGROUND . After primary treatment for cryptococcal meningitis, patients with the acquired immunodeficiency syndrome (AIDS) require some form of continued suppressive therapy to prevent relapse . METHODS . We conducted a multicenter, randomized trial that compared fluconazole (200 mg per day given orally) with amphotericin B (1 mg per kilogram of body weight per week given intravenously) in patients with AIDS who had completed primary therapy for cryptococcal meningitis with amphotericin B (greater than or equal to 15 mg per kilogram) . To be eligible, patients had to have at least two negative cultures of cerebrospinal fluid immediately before randomization . The primary end point was relapse of cryptococcal disease as confirmed by biopsy or culture . RESULTS . Of 218 patients initially enrolled, 119 were assigned to fluconazole and 99 to amphotericin B . Twenty-three patients were found not to have met the entry criteria; six other patients assigned to amphotericin B did not receive it and were lost to follow-up . Of the remaining 189 patients, after a median follow-up of 286 days 14 of 78 receiving amphotericin B (18 percent) and 2 of 111 assigned to fluconazole (2 percent) had relapses of symptomatic cryptococcal disease (P less than 0.001 by Fisher's exact test) . There was a difference of 19 percent in the estimated probability of remaining relapse-free at one year between the fluconazole group (97 percent) and the amphotericin B group (78 percent) (95 percent confidence interval, 7 percent to 31 percent; P less than 0.001) . Serious drug-related toxicity was more frequent in the amphotericin B group (P = 0.02), as were bacterial infections (P = 0.004) and bacteremia (P = 0.002) . CONCLUSIONS . Fluconazole taken by mouth is superior to weekly intravenous therapy with amphotericin B to prevent relapse in patients with AIDS-associated cryptococcal meningitis after primary treatment with amphotericin B.

Med Clin (Barc), 1992 Mar 14, 98(10), 361 - 5
{Cryptococcosis: presentation of 26 cases}; Pedrol E et al.; BACKGROUND: Cryptococcosis is more frequently observed since the appearance of the acquired immunodeficiency syndrome (AIDS) . AIDS has modified the clinical and evolutive forms of the disease . This study reviews the changes produced in the infection from the context of AIDS . METHODS: The present is a retrospective study (1985-1990) including patients presenting: 1) a positive latex agglutination test (serum or spinal fluid) or 2) a Sabouraud culture positive for cryptococcus . Clinical histories were revised collecting clinical, radiologic, analytic, therapeutic and evolutive data . RESULTS: Twenty-six patients (21 males) were included in the study . Twenty patients had the human immunodeficiency virus . The clinical picture was: 22 cases with cryptococcal meningitis (13 with hematogenous participation), 3 with pulmonary cryptococcosis and one with disseminated cryptococcosis without meningeal involvement . The patients with AIDS had: greater frequency of positive hemocultures, higher serologic titers and fewer with the meningeal syndrome . The number of T4 lymphocytes was lower than 150 elements/ml in AIDS patients . In 17 patients treatment with amphotericin B and 5-fluorocytosine was administered, 5 received amphotericin B and two fluconazole and two did not receive the above since they had not been diagnosed alive . There were 6 deaths and 10 relapses in 6 AIDS patients and none in the remaining patients . CONCLUSIONS: The incidence of cryptococcosis has increased as a consequence of AIDS . In these patients the disease occurs in advanced stages of immunodeficiency and frequently in disseminated, severe and paucisymptomatic forms . Treatment is usually effective although a maintenance therapy is required to avoid relapse.

Antimicrob Agents Chemother, 1992 Mar, 36(3), 647 - 50
Rapid and sensitive assay for fluconazole which uses gas chromatography with electron capture detection; Rege AB et al.; Fluconazole, an orally active antifungal agent, has been shown to be clinically beneficial for maintenance therapy of cryptococcal meningitis . A sensitive gas-liquid chromatographic assay with electron capture detection, which required only a single extraction step and precluded any pretreatment of the chromatographic column, was developed for fluconazole . The assay was linear from 0.1 to 20 micrograms/ml, with a correlation coefficient of 0.999 . The intraassay and interassay coefficients of variation were less than 9% . The measured values on average were within 8% of the target values . The extraction recoveries ranged from 87 to 106% . Steady-state plasma fluconazole levels (mean +/- standard deviation) in three AIDS patients with cryptococcal meningitis receiving 200 mg of fluconazole per day ranged from 8.95 +/- 1.32 to 11.41 +/- 0.63 micrograms/ml and were within the expected range for this dosing rate, on the basis of previous studies . The ratio of fluconazole concentration in cerebrospinal fluid to fluconazole concentration in plasma in one patient receiving 400 mg/day was 0.73 at steady state and was consistent with published reports.

Urology, 1992 Mar, 39(3), 289 - 91
Acquired immunodeficiency syndrome manifesting as prostate nodule secondary to cryptococcal infection; Adams JR Jr et al.; We report the first case of acquired immunodeficiency syndrome (AIDS) presenting as prostate nodularity secondary to mycotic granulomatous prostatitis which mimicked prostatic cancer on digital rectal examination . Transrectal ultrasonography revealed hypoechoic areas in the peripheral zone, which on biopsy specimen were found to represent cryptococcal infection . Subsequent serologic evaluation of the patient confirmed human immunodeficiency virus (HIV) positivity and later AIDS developed in the patient.

Antimicrob Agents Chemother, 1992 Mar, 36(3), 690 - 2
Use of high-dose fluconazole as salvage therapy for cryptococcal meningitis in patients with AIDS; Berry AJ et al.; Eight patients with AIDS were treated orally with 800 mg of fluconazole daily for cryptococcal meningitis for a mean duration of 4.5 months . Previous antifungal treatment had failed for all of the patients . No major toxicity was observed . Three patients died from cryptococcal infection . High-dose fluconazole may be effective salvage therapy for cryptococcal meningitis.

Nihon Kyobu Shikkan Gakkai Zasshi, 1992 Mar, 30(3), 393 - 401
{Clinical and pathological investigation of opportunistic pulmonary mycoses in autopsy cases}; Mashimoto H et al.; Clinical and pathological investigations were performed in 58 cases of opportunistic pulmonary mycoses diagnosed at autopsy during the 10 years between 1979 and 1988 at Sasebo General City Hospital . The following findings were obtained . 1) The incidence of opportunistic pulmonary mycoses during the 10 years was 7.7%, with a significant increase in the incidence of fungal infections during the last 5 years of the study . The incidence of pulmonary mycoses was higher in patients with blood dyscrasia than in those with solid tumor or benign disease (p less than 0.001) . 2) Administration of steroid hormone and anticancer drugs were suspected to be causative factors in the development of pulmonary aspergillosis and cryptococcosis, but not in candidiasis . 3) Characteristic radiographic patterns and clinical symptoms were absent in cases of pulmonary candidiasis due to the small size of the lesions and the high incidence of other complicating pulmonary infections and edema . 4) The most common initial roentgenographic pattern in opportunistic pulmonary aspergillosis was localized infiltrate, subsequently progressing to either multifocal infiltrates or cavitation . 5) The initial symptom in opportunistic pulmonary aspergillosis was usually high fever, and the radiographic abnormalities appeared later . The median duration between onset and death in 19 patients with pulmonary aspergillosis was 23.1 days . 6) Pulmonary aspergillosis should be suspected in the compromised host with high fever refractory to antibiotics and pulmonary infiltrates . Empiric antifungal therapy should be initiated at an early stage for the best chance for survival.

J Infect, 1992 Mar, 24(2), 185 - 9
Raised intracranial pressure and visual complications in AIDS patients with cryptococcal meningitis; Johnston SR et al.; The clinical course of cryptococcal meningitis in AIDS shows some important differences from the features of the illness in non-AIDS patients . Complications such as raised intracranial pressure and visual impairment that are recognised in non-AIDS patients may be less frequent in those with AIDS . Persistent intracranial hypertension should be managed actively to prevent visual impairment . In AIDS patients, in whom ventriculo-peritoneal shunts carry additional risks, acetazolamide can be used successfully to lower the CSF pressure and prevent visual lossPIP: 2 AIDS patients are described who had cryptococcal meningitis accompanied by increased intracranial pressure (ICP) and visual complications, a finding thought to be relatively rare in AIDS . Of the 2-6% of AIDS patients who develop cryptococcal meningitis, many have disseminated and recurrent infections . The 1st case was a 45-year old Ugandan woman who presented with stiff neck, and right VIth cranial nerve palsy . She was treated with amphotericin B and flucytosine with some improvement, but on the 9th day she awoke with headache, drowsiness, and total blindness, although no papilledema . Her CSF pressure was 40 cm H20 . She recovered after a month of intravenous chemotherapy and acetazolamide, but remained blind . Her sudden blindness was thought to be due to bilateral optic nerve infarction . The 2nd case was a 32-year old male homosexual, admitted with headache, vomiting, confusion, and drowsiness . He had stiff neck, and a CSF of 40 cm containing Cryptococcus neoformans . He was given amphotericin B, flucytosine, and has CSF drained every other day . On day 21 papilledema was seen in the right eye, and acetazolamide was started to lower CSF pressure . This patient recovered without loss of vision . 3 published series of cryptococcus meningitis in AIDS patients remarked about the low incidence of raised ICP, while 1 reported 9 of 27 with neurological and ophthalmic complications . The visual complications and increased ICP in these patients was thought to be due to inflammatory arachnoiditis or direct cryptococcal infiltration .

J Neurol Neurosurg Psychiatry, 1992 Mar, 55(3), 219 - 21
Tumour necrosis factor (TNF-alpha) and neurological disorders in HIV infection; Mastroianni CM et al.; Tumour necrosis factor (TNF-alpha) concentrations were determined in the CSF from 42 HIV-infected patients, with or without CNS involvement . In addition, 14 subjects with various neurological disorders but without HIV antibodies were included as controls . Raised CSF concentrations of TNF-alpha (greater than 40 ng/l) were detected both in patients with AIDS dementia complex (ADC) (6/9) and with CNS opportunistic infections (10/19) and, less commonly, in HIV infected subjects without CNS diseases (2/14) and in anti-HIV negative controls (1/14) . The highest CSF concentrations of TNF-alpha (greater than 100 ng/l), however, were found in seven out of eight patients with cryptococcal meningitis . Although a role for TNF-alpha in demyelinating lesions associated with ADC has been suggested, our results indicate that a clear elevation of TNF-alpha in the CSF from HIV positive patients mostly occurs in acute inflammatory disorders, such as cryptococcal meningitis.

Clin Infect Dis, 1992 Mar, 14 Suppl 1, S54 - 9
Therapy for cryptococcal meningitis in patients with AIDS; Powderly WG; Treatment of cryptococcal meningitis in patients with AIDS with amphotericin B plus flucytosine is associated with a failure rate of 20%-30% . In the absence of chronic suppressive therapy, 40%-60% of patients develop recurrent disease . Recent comparative studies have evaluated fluconazole, a new triazole antifungal agent . In primary therapy, fluconazole is associated with response rates of 35%-60%, which are equivalent to those seen with amphotericin B alone . However, a smaller study suggested that amphotericin B plus flucytosine was superior to fluconazole alone . Both studies identified risk factors associated with a poor outcome; these factors include lethargy or obtundation at presentation, a high titer of cryptococcal antigen titer in the cerebrospinal fluid, and a low leukocyte count in the cerebrospinal fluid . Fluconazole is highly effective in suppressing relapses of cryptococcal meningitis . Itraconazole has been investigated less extensively in the treatment of cryptococcosis but offers promise . Future studies need to address alternative approaches to the management of acute cryptococcal disease and primary prophylaxis for cryptococcal infection in patients with AIDS.

Clin Infect Dis, 1992 Mar, 14 Suppl 1, S37 - 42
Overview of host defenses in fungal infections; Levitz SM; Humans have a broad array of host defense mechanisms against fungal invasion . Most serious mycoses occur in patients who have defects in one or more of these defenses . Defense mechanisms not related to the immune system include barriers created by the skin and mucous membrane, competition from the normal indigenous bacterial flora, mucociliary clearance mechanisms, and fungistatic products in serum such as metal chelators . Among the immune mechanisms, activation of the complement system and generation of an antibody response facilitates recognition of fungi by specific receptors on immune cells . Quantitative and qualitative disorders of phagocytic function predispose patients to the development of invasive aspergillosis and candidiasis . Impairment of cell-mediated immunity predisposes patients to cryptococcosis, histoplasmosis, coccidioidomycosis, and mucocutaneous candidiasis . An overexuberant inflammatory response to fungal antigens can result in morbidity and mortality because of damage to host tissues . Knowledge of the type of immunocompromise that is afflicting a patient enables the clinician to predict which mycoses the patient is likely to have and to which the patient is predisposed.

Clin Infect Dis, 1992 Mar, 14 Suppl 1, S11 - 22
Serodiagnosis of candidiasis, aspergillosis, and cryptococcosis; de Repentigny L; During the past decade, substantial progress has been made in the development of new approaches and methods for the serological diagnosis of the mycoses . Clinically relevant antigens have been adapted for use in immunoassays for the detection of specific antibodies, and methods that detect fungal antigens in body fluids have been progressively refined . Nevertheless, few of the novel serological techniques have as yet found widespread clinical use . Reasons for this apparent discrepancy include the paucity of clinical data that substantiate improved predictive value for disease of antibody tests that use specific immunodominant antigens . The usefulness of detection of antigenemia in invasive candidiasis and invasive aspergillosis has been limited by the rapid clearance of Candida mannan and Aspergillus galactomannan from serum, which results in only moderate sensitivity for disease . False-negative results are especially frequent when single serum samples are tested in cases where fungal infection is clinically suspected . The detection of antigen in samples of urine collected serially may circumvent this problem in the future . The limited dissemination of methods for the detection of fungal antigens is also due to the slow development of simple and reliable commercial kits.

Clin Infect Dis, 1992 Mar, 14(3), 666 - 72
Cryptococcal disease presenting as cellulitis; Anderson DJ et al.; Three immunocompromised patients presented with cellulitis as the primary manifestation of cryptococcal disease . Two were recipients of cadaveric renal transplants who were receiving immunosuppressive drug therapy . The other patient had profound lymphopenia and severe hypoalbuminemia due to intestinal lymphangiectasia . All had failed to respond to empiric therapy for presumed bacterial cellulitis before results of skin biopsy or aspiration were available for the correct diagnosis to be made . With administration of systemic antifungal therapy, two patients survived . Although other forms of cryptococcal involvement of the skin are not rare, cellulitis is seldom considered to be a cutaneous manifestation of the disease . Our cases and a review of the English-language literature indicate that Cryptococcus neoformans must be included in the differential diagnosis of cellulitis in immunocompromised patients and that the presence of cryptococcal cellulitis suggests disseminated cryptococcal disease . Prompt diagnosis and treatment may dramatically reduce mortality.

Infect Immun, 1992 Mar, 60(3), 754 - 61
Contribution of antibody in normal human serum to early deposition of C3 onto encapsulated and nonencapsulated Cryptococcus neoformans; Wilson MA et al.; Encapsulated and nonencapsulated cryptococci differ in their activation of the complement system . Incubation of nonencapsulated cryptococci in normal human serum (NHS) initiates both the classical and alternative pathways . This activation is characterized by an immediate, synchronous activation and binding of C3 to the yeast cells . Encapsulated cryptococci activate only the alternative pathway . This activation is characterized by a delayed (4 to 5 min), asynchronous activation and binding of C3 . We examined the properties of antibodies in NHS that mediate immediate, synchronous binding of C3 to nonencapsulated cryptococci and zymosan . Adsorption of NHS with nonencapsulated cryptococci or zymosan produced a 4- to 6-min delay in the kinetics for activation and binding of C3 from the adsorbed serum to each respective yeast cell . This delay was similar to the delay observed when nonencapsulated cryptococci or zymosan was incubated in NHS in which the classical pathway was blocked by chelation of Ca2+ . Proteins bound to serum-treated nonencapsulated cryptococci or zymosan were eluted and found to be predominantly immunoglobulin G (IgG), with lesser amounts of IgM . The eluted IgG could restore to adsorbed serum the rapid early kinetics for activation and binding of C3 characteristic of classical pathway initiation . Cross-adsorption showed that there was considerable cross-reactivity between the antibodies which restored rapid, early activation kinetics to NHS adsorbed with zymosan or nonencapsulated cryptococci . Encapsulated cryptococci were unable to adsorb the antibodies from NHS that mediated the rapid, early activation and binding of C3 to zymosan and nonencapsulated cryptococci . The latter results show that occlusion of antigenic sites at the cryptococcal cell wall is a newly recognized property that can be added to the repertoire of biological activities of the cryptococcal capsule.

Infect Immun, 1992 Mar, 60(3), 1101 - 8
Molecular and genetic analysis of URA5 transformants of Cryptococcus neoformans; Varma A et al.; Cryptococcus neoformans var . neoformans ura5 mutants were transformed with linearized or circular plasmids containing the C . neoformans orotidine monophosphate pyrophosphorylase gene . Following electroporation, randomly isolated transformants were analyzed for the mitotic and meiotic stability of uracil prototrophy . All stable transformants tested showed nonspecific ectopic integration . Uracil prototrophy in these transformants was stable through meiosis . Some of the stable transformants showed integration of both URA5 and vector sequences, while others lacked any vector sequences . Unstable transformants exhibited the presence of an autonomously replicating plasmid which had undergone significant sequence rearrangement . The autonomously replicating plasmid in the transformants was observed to be the same size or smaller than the transforming plasmid, was maintained in a linear form, and had acquired a genomic sequence(s) with homology to a sequence(s) on all the chromosomes . The conservation of a 300-bp sequence at the 5' end of the URA5 gene was observed in all the rearranged plasmids . These results suggest mechanisms of plasmid maintenance in C . neoformans that are different from those reported for other yeasts . The ura5 mutant was significantly less virulent than the wild type . The transformants did not recover virulence regardless of prototrophic stability.

Infect Immun, 1992 Mar, 60(3), 1084 - 8
Galactoxylomannans of Cryptococcus neoformans; James PG et al.; Galactoxylomannans (GalXMs) from single isolates of Cryptococcus neoformans serotypes A, B, and D were isolated from culture supernatants and then purified by affinity, ion-exchange, and gel-filtration chromatography . GalXMs are a group of closely related complex polysaccharides . GalXMs from serotypes A (9759 A) and C (3183 C) and an acapsular mutant of serotype D (Cap67 D) have similar galactose, xylose, and mannose molar ratios, but each has some unique structural features . GalXM9759 A and GalXM 3183 C were associated with a starchlike glucan that was removed during purification . Only a trace of glucose was detected in the Cap67 D GalXM . Gas-liquid chromatography-mass spectroscopy of per-O-methylated polysaccharides and 13C nuclear magnetic resonance spectroscopy showed that GalXM is a complex branched polysaccharide . The main chain consists of mannose or galactose or alternating mannose and galactose residues . Xylose is present only as nonreducing termini . Galactofuranose occurs only in 3183 C and Cap67 D, and it is always present as nonreducing termini.

In Vivo, 1992 Mar-Apr, 6(2), 183 - 93
Fungal infections in cancer patients: an escalating problem; Samonis G et al.; Major advances in anticancer treatment have contributed to an increased frequency of severe fungal infections in patients with neoplastic diseases . Neutropenia remains the most important among the predisposing factors related to the malignancy or its treatment . Most fungal infections are caused by the commonly recognized opportunistic fungi Candida spp and Aspergillus spp, and the pathogenic fungi Cryptococcus neoformans, Histoplasma capsulatum, Coccidiodes immitis, and less often by Blastomyces dermatidis . However, recently newer pathogens such as Pheohyphomycetes, Hyalohyphomycetes, Zygomycetes and other fungi of emerging importance such as Torulopsis glabrata, Trichosporon beigelii, Malassezia spp, Saccharomyces spp, Hansenula spp, Rhodotorula spp, and Geotrichum candidum have appeared as significant causes of infection in this patient population . The increasing frequency of fungal infections is of great concern because of the difficulties in diagnosis and treatment . Amphotericin B remains the mainstay of antifungal treatment despite its toxicity and limited efficacy . Liposomal Amphotericin B may be more effective and less toxic . The activity of the azoles in immunocompromised patients is low . New azoles such as fluconazole and itraconazole may show future promise . The availability of the new granulocyte colony stimulating factors which can shorten the duration of neutropenia could represent a significant improvement in the management of fungal infections in cancer patients . As a preventive measure, the invasive procedures that predispose to infections should be done only when absolutely necessary and frequent handwashing by hospital personnel remains an effective prophylactic procedure.

Southeast Asian J Trop Med Public Health, 1992 Mar, 23(1), 138 - 41
Endocarditis caused by Candida parapsilosis; Senba M et al.; The authors report a case of endocarditis caused by Candida parapsilosis . To the best of our knowledge, a case has not been described previously in Japan in the English literature . A battery of 8 peroxidase-labeled lectins was tested on sections of paraffin-embedded tissue to determine which lectin could be used in the microscopic diagnosis of C . parapsilosis . One lectin, from Archis hypoaea (PNA) was found to react with C . parapsilosis . On the other hand, C . albicans, Aspergillus, Mucor, and Cryptococcus did not react with A . hypoaea (PNA) . On fluorescence microscopic study, C . parapsilosis was not fluorescent, but other fungi were fluorescent when exposed to ultraviolet illumination . Therefore, we propose new procedures for identification of C . parapsilosis in tissue sections using lectin histochemistry and fluorescence microscopy.

Q J Med, 1992 Mar, 82(299), 223 - 34
The neurological features of HIV-positive patients in Glasgow--a retrospective study of 90 cases; Petty RK et al.; A retrospective study of the neurological problems arising in HIV-I seropositive patients in a single defined geographical area was undertaken . Ninety patients were referred for a neurological opinion from a total known HIV-I seropositive population of 436 . Minor problems were frequently encountered early in the course of disease (20 at CDC stage II, 12 at CDC stage III), including seizures related to drug abuse in six . The most frequent neurological problem in those patients in CDC group IV (58 patients) were the AIDS dementia complex (14 patients), an axonal sensorimotor neuropathy (12), toxoplasmosis (nine) and cryptococcal meningitis (three) . All patients with a structural lesion had appropriate focal signs on examination . The value and role of CT cranial scanning in the diagnosis of toxoplasmosis is discussed and the importance of recognizing potentially treatable causes of both intellectual impairment and cytomegalovirus-related neuropathies is stressed . This is the first report of an unselected series of patients at all stages of HIV-I related neurological disease from a single UK centre.

Clin Infect Dis, 1992 Mar, 14 Suppl 1, S161 - 9
Azole antifungal agents; Bodey GP; The discovery of the antifungal activity of azole compounds represented an important therapeutic advance . Miconazole, ketoconazole, and fluconazole are currently commercially available, and itraconazole has undergone extensive clinical evaluation . Because of its limited activity and toxicity, miconazole has been replaced by newer agents . Ketoconazole has proven useful in therapy for superficial infections and invasive infections caused by the pathogenic fungi . Among its disadvantages are limited absorption in the absence of gastric acid and its potential for drug-drug interactions . Fluconazole is the only azole available as oral and intravenous preparations . Unlike other azoles, it is only minimally metabolized in the liver and largely excreted in the urine as active drug . It is more effective than ketoconazole against superficial candidal infections and is the drug of choice for maintenance therapy for cryptococcal meningitis in patients infected with human immunodeficiency virus . An advantage of itraconazole is its activity against aspergillosis . It is also active against many infections caused by pathogenic fungi . Other azole compounds are at varying stages of preclinical and clinical investigation.

N Z Med J, 1992 Feb 26, 105(928), 49 - 51
Neurological disease in patients with human immunodeficiency virus infection; Gane EJ et al.; We followed prospectively all patients with HIV infection admitted to the infectious diseases ward at Auckland Hospital over a seven month period . Neurological manifestations of HIV infection were the primary reason for admission in 18 of the 55 patients (33%) . Diagnoses were usually presumptive, based on history, clinical findings, radiological appearances and response to empirical therapy . Eight patients had cerebral toxoplasmosis, three primary cerebral lymphoma, two cytomegalovirus retinitis, two HIV neuropathy, one cryptococcal meningitis, one HIV encephalopathy, and one HIV meningitis . Another patient with HIV infection was admitted to the neurology ward at Auckland Hospital with HIV myelopathy during the same seven month period . The median survival of the patients treated for presumptive toxoplasmosis was 7.5 months . Only two patients had not developed AIDS, one having HIV meningitis and the other HIV myelopathy, and in both, symptoms resolved spontaneously with no relapse at one year follow up . The spectrum of neurological manifestations of HIV infection is wide . Investigations to determine the most likely diagnosis are indicated and specific therapy may lead to both excellent palliation and prolonged survival.

Chest, 1992 Feb, 101(2), 586 - 8
Complex cryptococcal empyema; Tenholder MF et al.; Cryptococcus neoformans continues to present diagnostic and treatment challenges in patients with underlying malignant neoplasms . Cryptococcal empyema is a relatively rare complication of cryptococcal disease . It is important to distinguish whether uncontrolled malignancy or cryptococcal infection is responsible for the effusion . We used traditional diagnostic approaches, bronchoscopy and transthoracic fine needle aspiration, to verify the presence of the organism but continued to have treatment failure until adequate drainage was established.

Med Clin (Barc), 1992 Feb 8, 98(5), 184 - 6
{Use of magnetic resonance in the diagnosis of neuro-cryptococcosis in the acquired immunodeficiency syndrome: study of 4 patients}; Uterga JM et al.; Neuro-cryptococcosis is a common opportunistic infection in AIDS or HIV infected patients . From a series of 10 neuro-cryptococcosis the four of them studied by magnetic resonance (MR) are reported . In AIDS patients a high suspicion of opportunistic infection of the CNS is needed as exemplified by two of the four patients who only presented cephalalgia . The other two patients suffered additional symptoms and signs of meningeal and CNS involvement, such as nuchal rigidity, cranial nerve palsies, papilloedema, gait ataxia and dismetria . Diagnosis was achieved (confirmed) by a positive culture, serology or indian ink test in CSF . CT scan did not contribute to the diagnosis and management of the patients . In contrast MR, showed in three of them a peculiar pattern of small, confluent, high-signal lesions, roughly symmetrically placed in the basal ganglia and the internal capsule . They probably correspond to the dilated Virchow-Robin spaces through which torulae migrate from the subarachnoid space.

Infect Immun, 1992 Feb, 60(2), 602 - 5
Genetic association of mating types and virulence in Cryptococcus neoformans; Kwon-Chung KJ et al.; A pair of congenic Cryptococcus neoformans var . neoformans strains, B-4476 (a mating type) and B-4500 (alpha mating type), that presumably differ only in mating type was constructed . This pair and their progeny, five alpha type and five a type, were tested for virulence in mice . In the parent strains as well as the progeny, alpha type was clearly more virulent than a type . In addition, death tended to occur earlier among the alpha-strain-infected mice that died than among the mice that died by infection caused by a strains . These data strongly suggest the genetic association of virulence with mating type in this human fungal pathogen.

Enferm Infecc Microbiol Clin, 1992 Feb, 10(2), 97 - 102
{Cryptococcal meningitis and AIDS . Clinical description of 10 patients}; Aguirrebengoa L et al.; We have studied 10 patients with cryptococcal meningitis and AIDS . Nine of them were intravenous drug users and four have been previously diagnosed of AIDS . In 60% of them cryptococcal meningitis was the first opportunistic infection, and as group represented only 6.3% of our 158 patients with AIDS on the same period . The most common symptoms were: malaise (100%), headache (80%), fever (60%), meningeal signs (50%) . Two of them had focal neurological disease . CSF culture and serum cryptococcal antigen test were positive in 90%, the Indian ink in 77% and blood cultures in 30% of the cases, while indian ink preparation did it in 77% . MRI showed bilateral small lesions, deeply located, in 3 cases; it was also useful to prove optical tract lesions in a patient with blindness as a result of cryptococcal meningitis . We had treatment successes in 80% of the cases, all patients being treated with amphotericin B, alone in 4 and amphotericin B plus fluorocytosine in 6 . Two patients died within the first 2 weeks . Maintenance therapy with fluconazole was effective and well tolerated, with 3 patients dying from causes other than cryptococcal meningitis . We recorded a survival rate over 12 months in 33% of patients.

Intern Med, 1992 Feb, 31(2), 174 - 9
Analysis of cases of central nervous system fungal infections reported in Japan between January 1979 and June 1989; Mori T et al.; Data from 129 cases of central nervous systemic fungal infections reported in Japan between January 1979 and June 1989 were analyzed . Of 129 cases, 116 were cryptococcal meningitis, 6 candidal meningitis (including meningitis due to Trichosporon cutaneum) and 7 Aspergillus meningoencephalitis . Fifty-six of the patients with cryptococcal meningitis had an underlying systemic disease or condition . The overall survival rate was 72.4%, which was a markedly improved rate compared to earlier reports . Cryptococcal meningitis was treated most often with the combination of intravenous amphotericin B and 5-fluorocytosine and was associated with a survival rate of 81.8% . All 7 patients treated with fluconazole alone survived . Candidal meningitis occurred secondary to a shunt infection; some patients with candidemia did well when adequate therapy was instituted . Aspergillus meningoencephalitis is most often diagnosed at autopsy or in surgical specimens and the prognosis of Aspergillus meningoencephalitis is generally poor.

Arch Mal Coeur Vaiss, 1992 Feb, 85(2), 203 - 8
{Fungal myocarditis in acquired immunodeficiency syndrome}; Hofman P et al.; The authors report 8 cases of fungal myocarditis discovered at autopsy of a series of 118 patients with AIDS . The cardiac disease was symptomatic and responsible for death in 2 cases . Antemortem diagnosis of fungal infection was made on examination of bronchioloalveolar lavage, the cerebrospinal fluid or gastrointestinal biopsy . The demonstration of intramyocardial pathogens was postmortem in all cases . The organism was Candida albicans in 3 cases, Cryptococcus neoformans in 3 cases, and Aspergillus fumigatus in 2 cases . The lesions were not confined to the heart; multi-visceral fungal involvement was diagnosed at autopsy in all cases . Cryptococcal and Candida myocarditis have already been described in most autopsy series in AIDS, but Aspergillus myocarditis is very rare . These fungal myocarditis are usually clinically latent or masked by neurological or respiratory symptoms.

Acta Med Okayama, 1992 Feb, 46(1), 45 - 7
Cryptococcal pleural effusion in an HTLV-I carrier with Waldenstroem's macroglobulinemia; Taguchi H et al.; A 70-year-old woman with Waldenstroem's macroglobulinemia developed bilateral pleural effusions due to Cryptococcus neoformans . She was found to be a carrier of HTLV-I . It is speculated that the opportunistic infection occurred as the result of an impaired cellular immunity secondary to HTLV-I infection.

Rev Clin Esp, 1992 Feb, 190(3), 125 - 7
{Fluconazole treatment of cryptococcal meningitis associated with HIV infection . Presentation of 4 cases}; Roig P et al.; We present four cases of C . neoformans meningitis (CNM) in patients with Human Immunodeficiency Virus (HIV) infection treated with fluconazole p.o . at an initial dose of 400 mg followed by 200 mg/day during a follow up period ranging from 3 to 12 months, and who presented an excellent clinical evolution . When comparing them to our previous cases who were treated with Amphotericin-B in combination with 5-fluorocytosine, a decrease in mean hospital stay (p less than 0.001) and a smaller incidence of secondary effects were observed . Treatment with fluconazole seems to be an effective alternative in treatment of CNM . Future greater studies are needed to confirm this findings.

Oral Surg Oral Med Oral Pathol, 1992 Feb, 73(2), 171 - 80
Oral mycoses in HIV infection; Samaranayake LP; Oral mycoses in human immunodeficiency virus (HIV) infection are becoming increasingly common . Of these, oral candidiasis is by far the most prevalent; fewer than 10 cases of cryptococcosis, histoplasmosis, and geotrichosis have thus far been reported . Oral candidiasis is one of the earliest premonitory signs of HIV infection and may present as erythematous, pseudomembranous, hyperplastic, or papillary variants, or as angular cheilitis . Cumulative data from 23 surveys (incorporating 3387 adults) suggest that in general, oral candidiasis may develop in one third to half of HIV-seropositive persons . Almost equal numbers of cases manifest with either erythematous or pseudomembranous variants . These and related concepts pertaining to oral mycoses in HIV infection are reviewed.

Ophthalmic Surg, 1992 Feb, 23(2), 129 - 31
Isolated ocular cryptococcosis in an immunocompetent patient; Hester DE et al.; A 62-year-old woman without evidence of immunocompromise was evaluated for uveitis and a subretinal lesion in the right eye . Laboratory evaluation, including cerebrospinal fluid analysis, revealed no apparent cause . The diagnosis of subretinal cryptococcosis was established by transscleral needle biopsy of the subretinal mass . Treatment with intravenous amphotericin B and oral 5-flucytosine brought recovery of visual acuity to 20/30-1 and resolution of the inflammation . This patient demonstrates that ocular cryptococcal infection must be suspected, even in the absence of predisposing factors or systemic findings, and that subretinal fine-needle aspiration is an important diagnostic tool in this setting.

Genitourin Med, 1992 Feb, 68(1), 42 - 4
Cavitating pulmonary cryptococcosis developing in an HIV antibody patient despite prior treatment with fluconazole; Coker RJ et al.; Disseminated cryptococcosis developed in an HIV antibody positive patient who was taking fluconazole for oral candidiasis . This case highlights the poor response to therapy that may be seen, and the severe pulmonary complications that may ensue . The use of fluconazole prior to the development of cryptococcosis did not confer protection.

Neurosurgery, 1992 Feb, 30(2), 186 - 9; discussion 189-90
The efficacy of image-guided stereotactic brain biopsy in neurologically symptomatic acquired immunodeficiency syndrome patients; Levy RM et al.; A prospective series of 50 neurologically symptomatic human immunodeficiency infected patients with intracranial lesions who underwent image-guided stereotactic brain biopsy is presented . Patients were diagnosed with primary central nervous system lymphoma (14 patients), progressive multifocal leukoencephalopathy (14 patients), toxoplasmosis (13 patients), human immunodeficiency virus encephalitis (3 patients), infarction (2 patients), and 1 patient each with metastatic adenocarcinoma, metastatic melanoma, cryptococcoma, and atypical mycobacterial infection . Two of the patients with toxoplasmosis had a second intracranial abnormality . Two biopsies resulted in either descriptive diagnosis only or were nondiagnostic; the definitive diagnostic efficacy of image-guided stereotactic biopsy was thus 96% . No deaths were incurred as a result of biopsy . Four intraoperative or postoperative hemorrhages occurred; in only 1 patient was there a residual neurological deficit related to the surgery . Image-guided stereotactic biopsy may thus be considered both safe and effective in this patient population.

J Clin Microbiol, 1992 Feb, 30(2), 381 - 5
Antigenemia in paracoccidioidomycosis; Freitas-da-Silva G et al.; Severe forms of paracoccidioidomycosis (Pcm) are accompanied by intense immunological involvement characterized by depression of the cell-mediated immune response and by high levels of antibodies in serum with no protective function . These changes can be reversed by antifungal treatment . It has been suggested that antigens of Paracoccidioides brasiliensis released into the circulation during the active phase of the disease may be involved in the genesis of the changes in the immune response . In the present study, we evaluated the antigenemia of patients with Pcm using a competitive enzyme-linked immunosorbent assay (ELISA-c) capable of detecting 6 ng of antigen per ml of serum . Twenty-seven of 88 serum samples tested gave positive results, with the highest frequency of positivity being detected in patients with the severe acute form of the disease; these patients had the highest antigen levels (0.03 to 3.4 micrograms/ml) . Follow-up of one case showed a correlation between antigen levels in serum and evolution of the disease . False-positive reactions were observed in sera from patients with histoplasmosis, aspergillosis, and cryptococcosis . The results indicate that the described method has potential for clinical application, especially with respect to the evaluation of disease activity . Quantification of fungal antigens in the serum of patients with active Pcm represents an objective parameter for the study of the physiopathology of the disease.

Wei Sheng Wu Xue Bao, 1992 Feb, 32(1), 68 - 71
{An urease negative Cryptococcus neoformans}; Li A et al.; We report an urease negative Cryptococcus neoformans derived from pigeon dropping . This isolate produced brown pigmented colonies on cornmeal Tween-80 agar with 300 micrograms/ml caffeic acid, but was failure to hydrolyze urea . More identification tests were performed for this isolate, such as assimilation and fermentation of carbohydrates, nitrate assimilation, production of starch like compound, growth on GCP medium, germ tube formation and inoculation of mice, ect . Most of the results showed that the microbiological characteristics of the isolate were typical of C . neoformans except for negative urease test . Even though there has been a report about an urease negative C . neoformans derived from an AIDS patient, but we have never found any report about isolation from pigeon dropping or nature environment . We should pay attention to the exist of this atypical strain of C . neoformans in nature environment and the possibility of infection to human being . Additionally, we also be aware of the possibility of neglect when this urease negative C . neoformans is identified with urease test.

AIDS, 1992 Feb, 6(2), 191 - 4
Primary prophylaxis with fluconazole against systemic fungal infections in HIV-positive patients; Nightingale SD et al.; OBJECTIVE: To investigate the efficacy of fluconazole prophylaxis against systemic fungal infections in HIV-positive patients . DESIGN: Open label treatment compared with historical controls . SETTING: Patients were seen at the Parkland Memorial Hospital HIV Clinic, Dallas, Texas, USA between 1 March 1990 and 28 February 1991 . PATIENTS, PARTICIPANTS: Three hundred and thirty-seven historical controls were followed for 157 patient-years, and 329 fluconazole-treated patients for 145 patient-years . INTERVENTIONS: Fluconazole (100 mg daily) was administered to all patients with CD4 lymphocyte counts less than 68 x 10(6)/l seen at our HIV clinic after 1 March 1990 . MAIN OUTCOME MEASURES: Lysis-centrifugation blood cultures were recorded monthly for all patients during both study periods . RESULTS: Twenty infections (16 cryptococcosis, four histoplasmosis) occurred in 337 historical reference control patients (product-limit 1-year incidence, 7.5 +/- 2.0/year) . Four infections (one cryptococcosis, three histoplasmosis) occurred in the treated patient group (product-limit 1-year incidence, 1.8 +/- 0.9/year) . CONCLUSIONS: Fluconazole warrants further evaluation for prophylaxis against systemic fungal infections in HIV-positive patients.

J Med Assoc Thai, 1992 Feb, 75(2), 85 - 8
Itraconazole in the treatment of cryptococcal meningitis; Chotmongkol V et al.; The results of an open study of the efficacy of oral itraconazole therapy in 8 patients with cryptococcal meningitis are reported . Therapy is monitored by clinical response with culture, indian ink stain and cryptococcal antigen testing of CSF . Four (50%) of eight patients were cured, two (25%) had partial response, and two (25%) failed . One patient had a relapse but responded to retreatment . No toxicity was observed . Itraconazole is, therefore, suggested as a new treatment for cryptococcal meningitis.

AIDS, 1992 Feb, 6(2), 185 - 90
Itraconazole compared with amphotericin B plus flucytosine in AIDS patients with cryptococcal meningitis; de Gans J et al.; OBJECTIVE: We conducted a comparison of itraconazole versus amphotericin B plus flucytosine in the initial treatment of cryptococcal meningitis in patients with AIDS and established the efficacy of itraconazole as maintenance treatment . DESIGN: The trial was a prospective, randomized, and non-blinded study . SETTING: The study was performed at an academic centre for AIDS, Amsterdam, The Netherlands . PATIENTS, PARTICIPANTS: Twenty-eight HIV-1-seropositive men with a presumptive diagnosis of cryptococcal meningitis, randomized between 5 February 1987 and 1 January 1990, were included for analysis . INTERVENTIONS: Oral itraconazole (200 mg twice daily), versus amphotericin B (0.3 mg/kg daily) intravenously plus oral flucytosine (150 mg/kg daily) was administered for 6 weeks followed by maintenance therapy with oral itraconazole (200 mg daily) to all patients . MAIN OUTCOME MEASURES: Outcome measures were a complete or partial response, recrudescence and relapse . RESULTS: A complete response was observed in five out of the 12 patients who completed 6 weeks of initial treatment with itraconazole versus all 10 patients who completed treatment with amphotericin B plus flucytosine (P = 0.009) . A partial response was observed in seven out of the 14 patients assigned to itraconazole . During maintenance therapy, recrudescence (n = 6) or relapse (n = 1) occurred in seven out of the 12 patients initially assigned to itraconazole, whereas two relapses occurred among nine patients initially treated with amphotericin B plus flucytosine (P = 0.22); recurrence of clinical symptoms was significantly related to a positive cerebrospinal fluid culture at 6 weeks (P = 0.003) . CONCLUSION: Itraconazole is less effective compared with amphotericin B plus flucytosine in achieving a complete response in initial therapy in AIDS patients with cryptococcal meningitis.

Am Rev Respir Dis, 1992 Feb, 145(2 Pt 1), 424 - 9
Tissue distribution and antifungal effect of liposomal itraconazole in experimental cryptococcosis and pulmonary aspergillosis; Le Conte P et al.; We studied the tissue distribution and in vivo antifungal effect of itraconazole, incorporated into pure dipalmitoylphosphatidylcholine (DPPC) multilamellar liposomes and administered intravenously . Eighty percent of the itraconazole was associated with DPPC . Drug levels in lung, brain, and liver, obtained after intravenous administration of tritiated itraconazole, were higher when the drug was administered intravenously as liposomal than when it was dissolved in cyclodextrin . Administration of the liposomal formulation also led to higher and sustained levels of intact itraconazole in serum . Efficacy was assessed in DBA/2 mice infected intravenously with 3 x 10(6) Cryptococcus neoformans, an inoculum responsible for early fatal pneumonia, or 3 x 10(5) C . neoformans, leading to delayed meningitis . In pneumonia, 20 mg/kg of liposomal itraconazole was more effective on survival than the same dose given intravenously in cyclodextrin or twice the dose administered orally dissolved in polyethylene glycol 200 . In meningitis, liposomal itraconazole was also more efficient than the drug dissolved in cyclodextrin . These results were confirmed by colony counts in the brain and lung of infected mice . In immunosuppressed OF1 mice infected after inhalation of Aspergillus fumigatus spores, liposomal itraconazole (20 mg/kg x 3) was the only effective treatment . We conclude that intravenous liposomal delivery of itraconazole enhances both concentrations in infected tissues and the in vivo efficacy of the drug . Such passive targeting of antifungal agents other than amphotericin B might be helpful in the treatment of severe systemic mycoses, especially in the case of lung or brain involvement.

Vet Immunol Immunopathol, 1992 Jan 15, 30(2-3), 261 - 74
In vitro responses of cheetah mononuclear cells to feline herpesvirus-1 and Cryptococcus neoformans; Miller-Edge MA et al.; In vitro T cell function by domestic cats and cheetahs to two common pathogens, feline herpesvirus-1 (FHV-1) and Cryptococcus neoformans, was assessed . Peripheral blood mononuclear cells (PBM) were stimulated with two strains of UV-inactivated FHV-1, whole heat-killed organisms or capsular antigen of Cryptococcus neoformans, and proliferative responses measured . As a group, cheetah PBM responded significantly poorer than domestic cat PBM when cultured with FHV-1 . However, individual cheetah responses varied widely . Supplementation of cultures with exogenous interleukin 2 (IL-2) significantly increased the level of response of individual cheetahs to both strains of FHV-1 . Cheetah sera contained slightly higher neutralizing antibody titers to FHV-1 than did domestic cat sera, suggesting that B cells function adequately in cheetahs . When stimulated with Cryptococcus neoformans, both species had similar incidences of positive proliferative responses . These data demonstrate that cheetahs exhibit heterogeneous responses to specific antigens, similar to domestic cats . However, a lower group response to FHV-1 in cheetahs suggests species differences occur . In addition, level of variability in major histocompatibility complex (MHC) class I-like genes, as determined by Southern blot hybridization, does not appear to correlate with a uniform response in in vitro functional assays . Therefore, additional mechanisms influence the final outcome of the immune response.

N Engl J Med, 1992 Jan 9, 326(2), 83 - 9
Comparison of amphotericin B with fluconazole in the treatment of acute AIDS-associated cryptococcal meningitis . The NIAID Mycoses Study Group and the AIDS Clinical Trials Group; Saag MS et al.; BACKGROUND . Intravenous amphotericin B, with or without flucytosine, is usually standard therapy for cryptococcal meningitis in patients with the acquired immunodeficiency syndrome (AIDS) . Fluconazole, an oral triazole agent, represents a promising new approach to the treatment of cryptococcal disease . METHODS . In a randomized multicenter trial, we compared intravenous amphotericin B with oral fluconazole as primary therapy for AIDS-associated acute cryptococcal meningitis . Eligible patients, in all of whom the diagnosis had been confirmed by culture, were randomly assigned in a 2:1 ratio to receive either fluconazole (200 mg per day) or amphotericin B . Treatment was considered successful if the patient had had two consecutive negative cerebrospinal fluid cultures by the end of the 10-week treatment period . RESULTS . Of the 194 eligible patients, 131 received fluconazole and 63 received amphotericin B (mean daily dose, 0.4 mg per kilogram of body weight in patients with successful treatment and 0.5 mg per kilogram in patients with treatment failure; P = 0.34) . Treatment was successful in 25 of the 63 amphotericin B recipients (40 percent; 95 percent confidence interval, 26 percent to 53 percent) and in 44 of the 131 fluconazole recipients (34 percent; 95 percent confidence interval, 25 percent to 42 percent) (P = 0.40) . There was no significant difference between the groups in overall mortality due to cryptococcosis (amphotericin vs . fluconazole, 9 of 63 {14 percent} vs . 24 of 131 {18 percent}; P = 0.48); however, mortality during the first two weeks of therapy was higher in the fluconazole group (15 percent vs . 8 percent; P = 0.25) . The median length of time to the first negative cerebrospinal fluid culture was 42 days (95 percent confidence interval, 28 to 71) in the amphotericin B group and 64 days (95 percent confidence interval, 53 to 67) in the fluconazole group (P = 0.25) . Multivariate analyses identified abnormal mental status (lethargy, somnolence, or obtundation) as the most important predictive factor of a high risk of death during therapy (P less than 0.0001) . CONCLUSIONS . Fluconazole is an effective alternative to amphotericin B as primary treatment of cryptococcal meningitis in patients with AIDS . Single-drug therapy with either drug is most effective in patients who are at low risk for treatment failure . The optimal therapy for patients at high risk remains to be determined.

Lancet, 1992 Jan 4, 339(8784), 21 - 3
Enhancement of HIV-1 infection by the capsular polysaccharide of Cryptococcus neoformans; Pettoello-Mantovani M et al.; Patients with AIDS who become infected with Cryptococcus neoformans have a poor prognosis . We speculated that the presence of cryptococcal capsular polysaccharide may enhance HIV-1 infection . In an in-vitro study, the presence of cryptococcal polysaccharide significantly increased (p less than 0.05) production of p24 antigen after infection of H9 cells with HIV-1-infected H9 cells . We also found similar results when lymphocytes from an HIV-1-infected patient were co-cultured with mononuclear cells from an uninfected individual . Our findings suggest a new pathogenic role for the capsular polysaccharide--namely, the capacity to enhance HIV-1 infectivity.

Mayo Clin Proc, 1992 Jan, 67(1), 69 - 91
Antifungal agents used for deep-seated mycotic infections; Terrell CL et al.; The increased use of immunosuppressive regimens in organ transplantation and in the treatment of malignant lesions and the epidemic of acquired immunodeficiency syndrome (AIDS) are major reasons for the greater prevalence of fungal infections seen in clinical practice during the past decade . The traditional cornerstone of antifungal treatment, amphotericin B, continues to play a major role in deep-seated mycotic infections . The indications for intravenously administered miconazole have become limited . Orally administered flucytosine remains useful in certain infections, particularly cryptococcal meningitis . The new orally administered antifungal agents ketoconazole and fluconazole have been approved for clinical use and have supplanted amphotericin B in certain situations . Investigational antifungal agents, including liposomal amphotericin B, itraconazole, and saperconazole, hold promise for the future . Active investigation in the development of new antifungal agents is expected to continue.

Am J Cardiovasc Pathol, 1992, 4(1), 25 - 30
AIDS and the heart in the Caribbean: a silent entity; Altieri PI et al.; PIP: Autopsies were performed by the cardiac pathology laboratory of 74 of 100 consecutive AIDS patients who died in Puerto Rico . The 32 with cardiac pathology are reviewed here . There were 27 males and 5 females, averaging 33 years old . 84% were heroin users and/or homosexual, and of the remaining 16%, 2 had heroin users and/or homosexual, and of the remaining 16%, 2 had received blood transfusions . The immediate cause of death was either respiratory or nervous system failure . One case of pericardial effusion (300 ml) associated with pleural effusion and ascites was found, but it was not clinically evident . 6 had cardiomegaly defined by cardiac mass 350 gm in males or 300 gm in females . There were no EKG findings other than sinus tachycardia with occasional ventricular premature beats . The most common pathological finding was nonspecific myocarditis . There were 5 cases with histoplasma showing cardiac foci of histiocytes, 3 with cardiac toxoplasma foci, 3 with mycobacterium granulomas in the myocardium or pericardium, 2 with cytomegalovirus myocarditis with intranuclear inclusions, 2 with cryptococcus neoformans, and 1 with atypical mycobacteria in the myocardium . 2 additional patients had coagulation necrosis of myocardial fibers . These results indicate that myocarditis is common in AIDS patients in Puerto Rico, especially in intravenous heroin users, and its causes are multiple . The clinical picture in terms of congestive heart failure or arrhythmias, however, is silent .

Appl Biochem Biotechnol, 1992 Spring, 34-35, 135 - 48
Hemicellulose bioconversion to polyanionic heteropolysaccharides; Tanenbaum SW et al.; Anionic polysaccharides, traditionally obtained from plant or algal sources, have a variety of commercial uses . Such gums from microorganisms have received increased recent interest . We have initiated a program to investigate the bioconversion of pentosans to rheologically useful anionic extracellular polysaccharides (AEPS) . A number of earlier-described species, including Cryptococcus laurentii, Klebsiella pneumoniae, Arthrobacter viscosus, and Pseudomonas ATCC 31260, appear to have potential in this regard . These organisms can individually convert either xylose, enzymatic oligomeric hemicellulose digests, dilute mineral acid hemicellulose ("TVA") hydrolysates, or a five-monosaccharide mixture simulating sulfite process liquors to AEPS . The formation parameters, compositions, mol-wt distributions, and the intrinsic viscosities of these purified AEPS are exemplified . Substitution of pentose as the major substrate for glucose can result in changes in mol-wt distribution or in the percentage of noncarbohydrate substituents in some AEPS . Pursuit of these observations may lead to interesting structure-property relationships and toward rheological applications for pentosan-derived AEPS.

Arkh Patol, 1992, 54(1), 59 - 62
{Morphologic manifestations of cutaneous and visceral cryptococcosis}; Polianko NI et al.; It is a review of the literature plus the description of the three cases of the skin and visceral cryptococcosis diagnosed after the histologic examination of surgical and biopsy material . As clinical diagnosis is difficult, the microscopy of glasses-"prints" from damaged organs stained with a black dye for a rapid revealing of cryptococci is recommended . An important role of hormonal preparations and antibiotics withdrawal is pointed out as their use activates the fungal flora.

Arkh Patol, 1992, 54(1), 56 - 9
{Brain cryptococcosis in HIV infection}; Vlasiuk VV et al.; A 30-year-old female with HIV-infection (AIDS-stage) died with generalized, including meningoencephalitis, infection . Fungi found in the brain were identified as Cryptococcus neoformans . Fungal cells were also found in the lungs and in the necrotic phlegmon of soft tissue i . e . there was a generalized Cryptococcus infection.

Antimicrob Agents Chemother, 1992 Jan, 36(1), 217 - 9
Comparison of SCH 39304 and its isomers, RR 42427 and SS 42426, for treatment of murine cryptococcal and coccidioidal meningitis; Allendoerfer R et al.; SCH 39304 (304) and its isomers, SCH 42426 (426) and SCH 42427 (427), are new orally administered antifungal azole derivatives . In this study, we compared the efficacy of 304 with that of 426 and 427 in murine models of cryptococcal and coccidioidal meningitis . On day 18 postinfection with Cryptococcus neoformans, controls showed 80% mortality . The 50% protective doses calculated at this day were 0.56 mg of 304 per kg of body weight, 23.5 mg of 426 per kg, and 0.11 mg of 427 per kg . Controls with coccidioidal meningitis all succumbed, and treated mice at the same time point showed 50% protective doses of 10.8 mg/kg for 304, 200 mg/kg for 426, and 2.1 mg/kg for 427 . We conclude that isomer 427 is five times as potent, whereas 426 is 1/50th as potent as 304 in these experimental mycoses.

J Acquir Immune Defic Syndr, 1992, 5(6), 600 - 4
Oral SCH 39304 as primary, salvage, and maintenance therapy for cryptococcal meningitis in AIDS; Lee BL et al.; To determine the efficacy and toxicity of SCH 39304 in the treatment and suppression of cryptococcal meningitis, we conducted a prospective, noncomparative study in three groups of patients: patients with acute cryptococcal meningitis, patients with acute cryptococcal meningitis in whom other therapies have failed (salvage), and patients who required maintenance therapy . As primary therapy, the patients received up to 14 days or 1 g of amphotericin B followed by SCH 39304 200 mg once daily for 12 weeks . As maintenance therapy, the patients received SCH 39304 600 mg once weekly for 12 months . Of five salvage patients, none completed the study . Two patients died, two patients clinically deteriorated, and one patient was noncompliant . Two of three patients with acute cryptococcal meningitis completed the 12-week primary therapy, and one patient was discontinued from therapy because of a skin rash (95% confidence interval, 14-100%) . All four patients who were receiving weekly maintenance therapy followed up to 27 weeks were clinically stable with no change in their serum cryptococcal antigen titer from baseline when the study was prematurely terminated . Elevation of liver function test results developed in three patients and skin rash developed in one patient . The unique pharmacologic and pharmacokinetic properties of SCH 39304 (low incidence of toxicity, long serum half-life, and good penetration into the cerebrospinal fluid) lend promise to pursue other triazole antifungals at higher doses as primary therapy and less frequent dosing for maintenance therapy.

J Med Vet Mycol, 1992, 30(2), 153 - 60
A nationwide survey of clinical laboratory methodologies for fungal infections; Goodwin SD et al.; Many hospitalized patients are at risk for fungal infections . In order to characterize present clinical laboratory experience and facilities for diagnosis and management of fungal infections, a nationwide survey of laboratory diagnostic methodologies was conducted . Data from calendar year 1988 were collected from 71 institutions (52 university teaching hospitals and 19 community hospitals) enrolled in the Drug Surveillance Network . Surveyed hospitals received 75,828 specimens for fungal culture in 1988, representing 18,705 positive cultures from 7373 patients . About 1.3% of patients admitted to teaching or community hospitals had positive fungal cultures, the most common isolates being Candida species . Yeast identification was most commonly performed by the germ tube test and carbohydrate assimilation testing . Dimorphic fungi were identified to the species level at 67% of hospitals . Cryptococcal antigen testing was available at all hospitals, and Candida serology testing was done at 55 institutions . A small number of hospitals performed antifungal drug concentration determinations for amphotericin B (n = 9), ketoconazole (n = 7) and flucytosine (n = 12) . Fungal susceptibility testing was available at 77% of hospitals, either within the institution or at an external laboratory . Laboratory testing for diagnosis and management of fungal infections represents a major laboratory investment . Proficiency in this area, along with expert clinical advice, will be needed to advance therapy of patients complicated with fungal infections during the next decade.

J Med Vet Mycol, 1992, 30(2), 133 - 44
Cryptococcosis in cats: clinical and mycological assessment of 29 cases and evaluation of treatment using orally administered fluconazole; Malik R et al.; Twenty-nine cats with naturally occurring cryptococcosis were evaluated prior to commencing oral fluconazole therapy (25-100 mg every 12 h) . Affected cats ranged from 2 to 15 years-of-age . Male cats (19; 66%) and Siamese cats (5; 21%) appeared to be over-represented in comparison to the hospital's cat population . Mycotic rhinitis was observed in 24 (83%) of the cases, although nasal cavity involvement was subtle in four animals . Disease of the skin and subcutaneous tissues was present in 15 cases (52%) and amongst these the nasal plane (seven cats) and bridge of the nose (seven cats) were most commonly involved . Primary infection of the central nervous system was not encountered, although one cat developed meningoencephalitis and optic neuritis as a sequel to longstanding nasal cavity disease . Antibodies against the feline immunodeficiency virus (FIV) were detected in eight cats (28%), and these cats tended to have advanced and/or disseminated disease . There was a tendency for cats to develop cryptococcosis during the Australian summer . Organisms were cultured from 27 cases . Cryptococcus neoformans var . neoformans was isolated from 21 cats, while C . neoformans var . gattii was identified in the remaining six . The response to oral fluconazole was excellent in this series, which included many cats with advanced, longstanding or disseminated disease . The fungal infection resolved in all but one advanced case which died after only 4 days of therapy . A dose of 50 mg per cat, given every 12 h, produced a consistently good response without side effects . Lower doses were effective in some cases, while 100 mg every 12 h was required to control the infection in one cat . Serum fluconazole levels obtained during chronic dosing (50 +/- 18 mg l-1, mean +/- SD; 50 mg per cat every 12 h) were highly variable (range 15-80 mg l-1) . Concurrent FIV infection did not impart an unfavourable prognosis, although affected cats often required prolonged courses of therapy.

J Med Vet Mycol, 1992, 30(2), 115 - 21
The interaction of Cryptococcus neoformans with primary rat lung cell cultures; Merkel GJ et al.; Conditions under which Cryptococcus neoformans adhered to and was internalized by primary lung epithelial cell cultures were studied . Adherence was affected by the yeast culture age, glucose concentration and growth temperature . Formalin or heat treatment did not affect yeast adherence . Trypsin treatment, however, inhibited adherence.

J Med Vet Mycol, 1992, 30(1), 71 - 8
Cryptococcal meningitis associated with acquired immunodeficiency syndrome (AIDS) in African patients: treatment with fluconazole; Laroche R et al.; Cryptococcal meningitis associated with acquired immunodeficiency syndrome (AIDS) is particularly common in tropical Africa . This could be explained by the dramatic increase in the number of human immunodeficiency virus (HIV) infections and the high prevalence of Cryptococcus neoformans var . neoformans in the domestic and general environment of HIV-positive and AIDS patients Meningoencephalitis is the usual and dominant clinical feature of cryptococcal infection in AIDS patients and 'slim disease', tuberculosis and candidiasis are the most common opportunistic infections associated with cryptococcal meningitis . In a group of 64 African patients with AIDS and cryptococcosis treatment with a daily dose of 400 mg fluconazole (FCA) during the acute phase showed a clinical cure in 63% of the evaluable patients . Mycological response to treatment with negative culture was found in 76% of our patients (at day 60-90) . The overall tolerance of FCA was excellent . This treatment was also used successfully for relapse of cryptococcal meningitis.

J Med Vet Mycol, 1992, 30(1), 61 - 9
Selection of ura5 and ura3 mutants from the two varieties of Cryptococcus neoformans on 5-fluoroorotic acid medium; Kwon-Chung KJ et al.; Spontaneous mutants requiring uracil were isolated from both varieties of Cryptococcus neoformans by plating on 5-fluoroorotic acid (5-FOA) medium . Of the 36 strains tested (18 var . neoformans and 18 var . gattii), 24 (12 of each variety) generated 5-FOA-resistant cells requiring uracil for growth . Six of the 12 C . neoformans var . gattii strains produced ura3 cells while the remaining six strains produced ura5 cells . None of the 12 strains produced both ura3 cells and ura5 cells . All 12 isolates of var . neoformans, however, produced ura5 cells and one of them produced ura3 as well as ura5 cells . A genetic lesion in the URA5 gene of an isolate of C . neoformans var . gattii was confirmed by complement with the cognate URA5 gene of C . neoformans var . neoformans . The ura3 isolates were tentatively identified by their ability to grow on a medium containing uridine but not on a medium with orotic acid or orotidine . Enzymatic assays for orotidine-5'-phosphate decarboxylase activity confirmed the isolates to be ura3 mutants . Hybridization analysis of total DNA, digested with EcoRI or StuI and probed with pURA5g2, revealed the presence of only one copy of URA5 in the strains of either variety, regardless of the prevalence of ura5 mutants . Extensive polymorphism was observed in the restriction patterns of the fragments containing the URA5 locus . The prevalence of spontaneously arising ura3 mutants among the isolates of C . neoformans var . gattii, but not among the isolates of C . neoformans var . neoformans, is one more biological difference that distinguishes the two varieties.

Skeletal Radiol, 1992, 21(2), 117 - 9
Case report 699 . Primary localized skeletal cryptococcosis (torulosis) of the right tibia at its proximal end; Ueda Y et al.; The case of a 58-year-old man with a normal immune status with primary localized skeletal cryptococcosis of the right tibia was presented . Radiologically it appeared as an osteolytic lesion with marginally indistinct borders in the epimetaphyseal region of the proximal tibia . Histologically, necrotizing granulomatous inflammation was associated with a prominent fibrohistiocytic reaction . The presence of cryptococci was confirmed by special stains . Clinicopathological features and the therapeutic aspects of this rare infective bone lesion were discussed . It is uncommon today, particularly in developed countries, to encounter a localized skeletal fungal infection . Therefore, radiologists and pathologists generally may be unfamiliar with the appearance of the lesion and tend not to consider the possibility of fungal osseous disease in the differential diagnosis . Unless it is remembered that fungal infection may cause a localized bone lesion with varied histological responses, the diagnosis may be overlooked, and bacteriologic proof may not be sought.

J Rheumatol, 1992 Jan, 19(1), 172 - 3
Cryptococcal olecranon bursitis in cirrhosis; Farr RW et al.; A 47-year-old man with cirrhosis developed a case of previously unreported olecranon bursitis due to Cryptococcus neoformans . Most patients with disseminated cryptococcosis have deficiencies in cell mediated immunity . Cirrhosis may be an independent risk factor because of impaired chemotaxis and phagocytosis.

Ann Med Interne (Paris), 1992, 143(3), 191 - 7
{The bone marrow in human HIV infection . A bioptic study of 125 cases}; Marche C et al.; Bone marrow biopsies from 125 patients at different stages of HIV infection were examined and the histopathological changes are described . Indications for biopsy included peripheral blood abnormalities, search for opportunistic pathogens, a suspected lymphoma or evaluation of its progression . Common histopathological features, suggestive of HIV infection but non-pathognomonic, were: severe hypercellularity (43.2%), myelodysplasia (74.4%), plasmocytosis (86.4%), and lymphocytic (36.8%) and histiocytic infiltrates with or without granulomas (20%) . Reticular fibrosis (58.6%), iron deposits (59.2%), vascular congestion and mucoid degeneration of fat (18.4%) were frequently observed . Hypoplasia was usually a late-occurring event and/or may have been iatrogenic . Opportunistic infections were detected in 8 patients: Mycobacterium avium intracellulare (4 cases), Mycobacterium tuberculosis (1 case), Cryptococcus neoformans (1 case), and Leishmania (1 case) . Neoplastic complications were found in 3 patients: Burkitt's lymphoma (1 case) and Hodgkin's disease (2 cases) . The pathophysiological mechanisms envisaged include the effect of HIV infection on precursor cells in the bone marrow.

J Acquir Immune Defic Syndr, 1992, 5(9), 883 - 9
Clinical and laboratory profile of AIDS in India; Kaur A et al.; The clinical features and results of laboratory investigations of the first 19 Indian patients with AIDS seen in our hospital are presented . Weight loss, fever, and diarrhea were the most common symptoms . Tuberculosis (TB) was the most common secondary infectious disease; among 13 patients, seven had only pulmonary TB, five had pulmonary and extrapulmonary TB, and one had only extrapulmonary TB . Oropharyngeal candidiasis was found in 11 patients . Other secondary infections were predominantly by virulent bacteria . Opportunistic infections other than candidiasis were infrequent; one patient had cryptococcosis, two had symptomatic cryptosporidiosis, one had noncoagulase-positive staphylococcus septicemia, and one had cytomegalovirus retinitis . Reduced lymphocyte counts (particularly of the CD4 subset), anemia, hypoalbuminemia, hyperglobulinemia, and elevated liver enzyme levels were frequent laboratory findings . Six patients are under follow-up, two are lost to follow-up, and 11 have died . Lymphocyte counts less than 500/mm3 were only seen in those patients who subsequently died . Response to antituberculosis therapy was good in several patients . Thus, the clinical profile of Indian patients with AIDS is not different from the common picture of patients of low socioeconomic and poor hygienic standards; patients presented with TB, undernutrition, and multiple infections . Therefore, a large population of patients with AIDS in India will not be recognized unless they are tested for evidence of HIV infection.

J Med Vet Mycol, 1992, 30(5), 407 - 8
Environmental isolation of Cryptococcus neoformans var . gattii from Eucalyptus tereticornis; Pfeiffer TJ et al.; As an extension of the previously established association between Cryptococcus neoformans var . gattii and Eucalyptus camaldulensis (River red gum) we have now found a similar relationship between C . neoformans var . gattii and the closely related Eucalyptus tereticornis (Forest red gum) . The global distribution of E . tereticornis is similar to that of E . camaldulensis.

J Med Vet Mycol, 1992, 30(5), 395 - 7
Isolation of Cryptococcus neoformans var . gattii from an Asian patient in France: evidence for dormant infection in healthy subjects; Dromer F et al.; We report the first case of cryptococcosis due to Cryptococcus neoformans var . gattii in France . This Cambodian, non-AIDS patient had been living in France for 23 years when he developed cryptococcosis due to C . neoformans serotype B in 1985 . It is possible that he was infected back in Asia or several months before, in Zaire, where he lived between 1981 and 1984 . To our knowledge, this is the second case providing clinical evidence for reactivation of latent infection with C . neoformans . The mechanism is probably similar to that for C . neoformans var . neoformans.

J Med Vet Mycol, 1992, 30(4), 309 - 15
Cryptococcal peritonitis in a CAPD patient; Morris B et al.; A 50-year-old diabetic woman with end-stage renal disease, who had been on continuous ambulatory peritoneal dialysis for 8 months, developed peritonitis caused by Cryptococcus neoformans var . neoformans . The patient was completely asymptomatic and infection was confirmed by detection of budding yeast cells in Gram-stained smears of turbid peritoneal fluid . The infection was cleared after intravenous fluconazole with delayed removal of the catheter . Fluconazole may be a suitable alternative drug in treating cryptococcal peritonitis.

Infect Immun, 1992 Jan, 60(1), 143 - 9
A 34- to 38-kilodalton Cryptococcus neoformans glycoprotein produced as an exoantigen bearing a glycosylated species-specific epitope; Hamilton AJ et al.; Three monoclonal antibodies (MAbs), all of the immunoglobulin G1 subclass, were raised against Cryptococcus neoformans by using the technique of cyclophosphamide ablation of B-cell responses against shared epitopes of the cross-reactive fungus Trichosporon beigelii . MAb 3C2 was reactive against the encapsulated and nonencapsulated isolates of C . neoformans var . neoformans by enzyme-linked immunosorbent assay (ELISA) and Western blot (immunoblot), and in addition to a 34- to 38-kDa determinant, it recognized a series of lower-molecular-weight species . 3C2 also reacted strongly with culture supernatant preparations of C . neoformans var . neoformans by ELISA . 3C2 showed no recognition of either T . beigelii or C . neoformans var . gattii antigens . Enzymatic deglycosylation followed by reaction with 3C2 on Western blots revealed that sialic acid was an integral part of the determinant, together with N-acetylglucosaminyl-asparagine and alpha-mannose . Proteolytic digestion showed that the epitope was pepsin sensitive and that it also contained tryptophan and glycine and/or leucine as determinants of recognition by 3C2 . The pI of the glycoprotein was 7.1 . Affinity chromatography-purified antigen did not exhibit proteolytic activity on sodium dodecyl sulfate-polyacrylamide substrate gels . Indirect fluorescence antibody tests revealed that 3C2 labelling was confined to the cell membrane and cytoplasm of yeasts . The remaining MAbs, 7H4 and 5G5, recognized both capsulated and nonencapsulated strains of C . neoformans var . neoformans by both ELISA and Western Blot, identifying linear determinants with molecular masses of 36 and 30 kDa . They were unreactive against culture supernatant antigen (exoantigen) from either variant of C . neoformans.

Acta Derm Venereol, 1992, 72(3), 182 - 4
Cutaneous cryptococcosis resembling molluscum contagiosum in a homosexual man with AIDS . Report of a case and review of the literature; Ghigliotti G et al.; A 43-year-old homosexual man with the Acquired Immunodeficiency Syndrome (AIDS) developed cutaneous molluscum contagiosum-like lesions on face, ears, neck, hands and feet . He was admitted to our unit with fever, malaise and headache . Cytologic examination of skin brushing revealed numerous encapsulated budding yeasts, identified as Cryptococcus neoformans . Such a finding calls for a cytologic examination of skin lesions in patient with AIDS who present with fever and headache, in order to rule out a potentially life-threatening fungal infection.

Rev Cubana Med Trop, 1992, 44(1), 29 - 33
{The diagnosis of cryptococcosis . A comparison of 2 latex systems for antigen detection}; Alvarez Bernal LP et al.; A latex reactive was designed for detecting Cryptococcus neoformans antigen . It was evaluated by a comparative study with a commercial system (Meridian Diagnostic, Inc.) . Total coincidence was observed with both latex systems after studying 3 sample groups: patients with cryptococcosis diagnosis, blood bank donors and patients with clinical signs of the disease . Sensitivity, specificity and stability of the latex reactives prepared were assessed . This diagnostic technique opens new perspectives for quick diagnosis in Cuba, especially for immunosuppressed patients . It will allow for timely treatment and at the same time will contribute to saving expenses in imports.

Agressologie, 1992, 33 Spec No 2, 77 - 80
{Rare opportunistic fungal diseases in patients with organ or bone marrow transplantation}; Herbrecht R et al.; Candidiasis, aspergillosis and cryptococcosis are the most common fungal infections in transplant recipients . However other fungal infections have been reported . Mucormycosis, Scedosporium infections, fusariosis and trichosporonosis represent the largest part of these rare mycosis . The clinical and mycological features are described here . In addition, cases of very uncommon mycosis, most of them only once reported, have been reviewed . Overall the diagnosis is difficult as mycological examinations are often negative till the disease is disseminated . Amphotericin B remains the reference treatment except in Scedosporium infections which respond more likely to azole antifungal agents . Despite the treatment the outcome is usually fatal.

Ann Pathol, 1992, 12(3), 165 - 73
{Histopathologic features of opportunistic infections of the small intestine in acquired immunodeficiency syndrome}; Michiels JF et al.; The frequency of the opportunistic infections of the duodenum in AIDS patients was determined by way of histologic study in 207 patients between January 1987 and June 1991 . All cases had serial paraffin sections, run through HES, PAS, Giemsa, Brown-Brenn, and Zieh-Neelsen stains, and 20 cases had in addition cytologic and electron microscopic study . 63 patients had opportunistic infections (10 cryptosporidiosis and 2 isosporiasis; 12 mycobacterial enteritis; 15 CMV enteritis; 7 candidosis; 7 intestinal microsporidiosis confirmed by electron microscopic examination; 12 Giardiasis; 3 duodenal leishmaniasis; 1 intestinal cryptococcosis) . Multiple concurrent infections were noted in 6 cases . A mild to severe villous atrophy was observed in 28 cases, associated with opportunistic infection . A patchy distribution of pathogen agent was noted in 34 cases, and 37 cases were associated with oesophagal candidosis . This study points out the value of histologic examination of intestinal biopsy for the diagnosis of systemic infections as well as of unusual parasitosis, and the necessity for multiple endoscopic biopsies because of the frequent patchy distribution of pathogens.

J Med Vet Mycol, 1992, 30(3), 257 - 9
Mycological findings in feline immunodeficiency virus-infected cats; Mancianti F et al.; Thirty-five FIV-seropositive cats and 55 FIV-seronegative matched cats were examined for yeasts (oropharyngeal swabs) and dermatophytes (hair brushings) . The frequency of isolation of Candida albicans and Cryptococcus neoformans was significantly higher in the former group . The only dermatophyte isolated was Microsporum canis . Its prevalence was three times higher among FIV-infected cats than among control animals.

Chemotherapy, 1992, 38 Suppl 1, 35 - 42
Opportunistic fungal infections in patients with acquired immune deficiency syndrome; Viviani MA; The recently developed antifungal agents itraconazole and fluconazole have been evaluated for primary and maintenance therapy for mycoses in patients with acquired immune deficiency syndrome (AIDS) in comparative and non-comparative trials . In oropharyngeal candidosis, ketoconazole may have to be given at a dose of 400 mg/day for comparable efficacy with fluconazole, 50 mg/day, because many patients with AIDS lack the gastric acid secretion necessary for drug absorption . Relapse rates were high . Itraconazole, 200 mg/day for 4 weeks, was as effective as ketoconazole, 400 mg/day, in achieving clinical remission and was better tolerated, but relapse rates were also high . An oral formulation of itraconazole in cyclodextrin has given clinical and mycological remissions in 39/39 patients after 7 days of treatment . In primary treatment of cryptococcosis, fluconazole is well tolerated, but is effective in only 50% of patients . Pilot studies of itraconazole, 200-400 mg/day, gave responses in 11/12 patients, of whom 8 had meningitis . Itraconazole combined with flucytosine gave a response in 12/13 patients, of whom 9 had meningitis . This combination shortened the time to cure . Both itraconazole and fluconazole are effective as maintenance therapy given after successful primary therapy of cryptococcosis . Itraconazole, 200 mg/day, was successful in preventing relapse in 34/39 patients over a mean 12-month period . The serum antigen titre fell progressively in 14, and fell to zero in 18 patients . Limited non-comparative trials suggest that triazoles are effective in coccidioidomycosis, and in particular that itraconazole is active against histoplasmosis in patients with AIDS; 8/9 patients with histoplasmosis responded to itraconazole, 400 mg/day, with a mean follow-up of 1 year.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemotherapy, 1992, 38 Suppl 1, 3 - 11
In vitro antifungal spectrum of itraconazole and treatment of systemic mycoses with old and new antimycotic agents; Van Cutsem J; Itraconazole is a lipophilic triazole with potent in vitro activity . It is also effective after topical, oral and parenteral administration . The antifungal activity of itraconazole has been evaluated against more than 6,500 different strains, belonging to more than 260 fungal species, using the serial decimal dilution test in fluid broth medium (brain-heart infusion broth) . Candida spp., Torulopsis spp., Cryptococcus neoformans, Pityrosporum spp . (Dixon broth), various other yeasts, dermatophytes, Aspergillus spp., Penicillium spp., Sporothrix schenckii, dimorphic fungi (mycelium phase and yeast phase), Phaeohyphomycetes, Entomophthorales and various Hyalohyphomycetes are sensitive . Most strains of Fusarium and Zygomycetes are poorly sensitive . Itraconazole was administered orally and parenterally in normal and immunocompromised guinea-pigs infected with C . albicans, Cr . neoformans, Histoplasma duboisii, S . schenckii, P . marneffei and A . fumigatus . It was effective in terms of both survival of the animals and elimination of the fungi from the various tissues . Itraconazole was superior to fluconazole in candidosis, cryptococcosis, sporotrichosis and aspergillosis, and to amphotericin B and to flucytosine in candidosis, cryptococcosis and aspergillosis . No comparative studies have yet been undertaken for other deep mycoses . The results of combination therapy with itraconazole and fluconazole in cryptococcosis were indifferent; with flucytosine or amphotericin B, additive or synergistic effects were seen in systemic candidosis, cryptococcosis and aspergillosis . No drug-related side-effects were observed after oral or parenteral administration of itraconazole.

Chemotherapy, 1992, 38 Suppl 1, 12 - 22
US experience with itraconazole in Aspergillus, Cryptococcus and Histoplasma infections in the immunocompromised host; Hostetler JS et al.; Itraconazole has emerged as an important new oral agent in the treatment of systemic fungal infections . This paper summarizes the data available on its use in aspergillosis, cryptococcosis and histoplasmosis, compiled in the United States with particular attention to the immunocompromised host . Data have been accrued in open-label studies including 57 patients with cryptococcal disease where the overall response rate among patients with meningitis was 86%, and in 28 patients (8 with acquired immune deficiency syndrome (AIDS) or human immunodeficiency virus (HIV) infection) with invasive aspergillosis where the overall response rates were 80% in patients without AIDS and 86% in patients with AIDS . Data are summarized on 6 patients with allergic bronchopulmonary aspergillosis, 5 of whom demonstrated marked improvement on therapy, and 12 patients with histoplasmosis including 8 with AIDS, 11 of whom responded and 1 recrudesced on therapy . In summary, itraconazole showed activity in human studies of aspergillosis, cryptococcosis and histoplasmosis with minimal toxicity . Itraconazole offers a new oral alternative to conventional amphotericin B therapy in these infections . Comparative studies are needed to clarify its role.

Ann Med Interne (Paris), 1992, 143(1), 43 - 9
{Neuropathology of the brain in 174 patients who died of AIDS in a Paris hospital 1982-1988}; Matthiessen L et al.; Between 1982 and 1988, 174 brains were systematically collected from consecutive, autopsied AIDS patients in a Parisian general hospital without neurology and psychiatry departments . The data obtained under these conditions provide reliable information on the frequency of central nervous system (CNS) involvement in a non-selected population of AIDS patients, most of whom were homosexuals (75.9%) . One or several lesions were observed in 148 cases (85%) . HIV encephalitis and/or leucoencephalopathy with multinucleated giant cells was found in 33 cases (18.9%) . Opportunistic infections were identified in 91 patients (52.3%): toxoplasmosis (65 cases; 37.3%), cytomegalovirus encephalitis (25 cases; 14.3%), cryptococcosis (9 cases; 5.8%), progressive multifocal leukoencephalitis (5 cases; 2.8%), candidosis (1 case) and tuberculosis (1 case) . Neoplasias were observed in 23 patients: primary (16 cases; 17.9%) or secondary malignant non Hodgkin's large B-cell lymphoma (3 cas; 1.1%), Kaposi's sarcoma (1 case) and glioma (3 cases; 1.1%) . Non-specific lesions (vasculitic, hemorrhagic, metabolic and especially microglial nodules) were common . During the 6 years of study, the rate of CNS involvement was constant . The number of toxoplasmosis cases per year was stable, however, evolutive forms were more prevalent between 1982 and 1986, whereas treated inactive lesions were seen most frequently thereafter . The opportunistic complications were often associated and it should be noted that HIV encephalitis was associated with one of several such infections in 85% of the patients . This high rate of association suggests that these opportunistic infections may play a role in the pathogenesis of HIV encephalitis.

Clin Infect Dis, 1992 Jan, 14(1), 165 - 74
Interaction of azoles with rifampin, phenytoin, and carbamazepine: in vitro and clinical observations; Tucker RM et al.; Twelve patients receiving therapy with an azole agent (ketoconazole, itraconazole, and/or fluconazole) for systemic mycoses experienced drug interactions with rifampin, phenytoin, and/or carbamazepine resulting in substantial decreases in azole concentrations in serum . All four patients receiving azoles and concurrent phenytoin and/or carbamazepine failed to respond to treatment or suffered a relapse of their fungal infection . Four of five patients with cryptococcosis who received itraconazole and rifampin responded despite decreases in their serum itraconazole concentrations; synergy between itraconazole and rifampin was documented by in vitro analysis of inhibition and of killing of Cryptococcus neoformans isolates from all patients receiving this combination . In contrast, two patients with coccidioidomycosis failed to respond to itraconazole/rifampin . Moreover, two patients with cryptococcosis suffered a relapse or persistence of seborrheic dermatitis while receiving itraconazole/rifampin . The latter combination showed synergy in vitro in the inhibition of the mycelial phase of Coccidioides immitis and, to a lesser extent, of the pathogenic spherule phase of this fungus; synergy in the killing of C . immitis was not noted, nor was synergy seen against Malassezia furfur, the purported etiologic agent of seborrheic dermatitis . These findings illustrate several drug interactions that may affect clinical outcome and that must be considered in the management of antifungal therapy.

J Acquir Immune Defic Syndr, 1992, 5(4), 333 - 40
Neurological complications of HIV-1-seropositive internal medicine inpatients in Kinshasa, Zaire; Perriens JH et al.; Because little was known about the prevalence of neurological complications of human immunodeficiency virus type 1 (HIV-1) infection in Africa, we conducted a cross-sectional study among consecutive admissions to the internal medicine wards of Mama Yemo Hospital in Kinshasa, Zaire . Of the 196 patients studied, 104 (53%) were HIV-1 seropositive, of whom 50 (48%) had stage 3 and 49 (47%) had stage 4 HIV-1 infection according to the provisional WHO staging criteria for HIV infection . Neuropsychiatric abnormalities were present in 43 (41%) of 104 HIV-1-seropositive patients . Of the HIV-1-seropositive patients, 9 (8.7%; 95% confidence interval, 4-16%) were diagnosed as having possible HIV-1-associated dementia complex, 1 (1%) as having possible HIV-1 myelopathy, and 3 (2.7%) as having possible HIV-1-associated minor cognitive/motor disorder . Definitive diagnoses could not be made because there were no facilities for neuroimaging and neuropathology . Meningitis caused by cryptococcus was diagnosed in six (5.6%) and by Mycobacterium avium in two (2%) of the HIV-1 seropositive patients . Acute onset hemiplegia, believed to be due to stroke, was present in four (4%) of the HIV-1-seropositive patients . The prevalence of other central nervous system opportunistic infections and mass lesions, especially toxoplasmic encephalitis, could not be assessed . In this population of Zairian inpatients, the prevalence of neurological complications of HIV-1 infection was similar to that observed in industrialized countries among patients with advanced HIV disease.

Rev Neurol (Paris), 1992, 148(12), 762 - 6
{Candida albicans meningitis and neurosarcoidosis}; Larnaout A et al.; We report a clinico-pathological case of neurosarcoidosis characterized by chronic meningitis, intracranial hypertension, bilateral optic atrophy, arthritis and enlargement of liver and lung hilar nodes . Synovial and supraclavicular node biopsies showed multiple non caseating nodules without tubercle bacilli, Candida albicans and Cryptococcus neoformans . Post-mortem examination showed a severe meningeal lymphoplasmocytic infiltration with numerous non-caseating nodules, several giant cells and presence of Candida albicans . There were also a periventricular infiltration of similar cells and numerous cerebral and cerebellar infarctions . We think that the Candida albicans meningitis was a consequence of the immunodepression of sarcoidosis and of corticosteroid therapy.

Australas J Dermatol, 1992, 33(2), 93 - 6
Cutaneous cryptococcosis: recurrence following oral fluconazole treatment; Cooper CM et al.; A case of recurrent cutaneous cryptococcosis in an immunocompromised patient is described . The patient presented with a non-healing cutaneous ulcer due to infection with Cryptococcus neoformans . Extensive investigation failed to reveal any evidence of associated systemic cryptococcosis . Treatment with oral fluconazole resulted in complete resolution of the ulcer but after several months a second cutaneous cryptococcal lesion appeared, strongly suggesting dissemination from an underlying systemic focus . This case illustrates the hazards associated with making a diagnosis of isolated cutaneous cryptococcosis and the necessity for prolonged follow-up of patients who present in this way.

Scand J Infect Dis, 1992, 24(6), 787 - 91
Cerebrospinal fluid levels of IL-6 in patients with acute infections of the central nervous system; Torre D et al.; Interleukin-6 (IL-6) activity was measured in the cerebrospinal fluid (CSF) of patients with acute bacterial or viral meningitis and in AIDS patients with various cerebral disorders . Increased levels of IL-6 were detected in the CSF of patients with bacterial meningitis . On the contrary, most of the samples from patients with viral meningitis (predominantly caused by mumps virus) had no detectable IL-6 activity in CSF . A moderate increase of IL-6 levels was detected in the CSF of AIDS patients with AIDS dementia complex (ADC), progressive multifocal leukoencephalopathy and cerebral toxoplasmosis . Moreover, higher levels of IL-6 were detected in the CSF of patients with cryptococcal meningitis . We conclude that the initial events of CSF inflammation in patients with acute viral meningitis are different from those in patients with acute bacterial meningitis, and the role of IL-6 is less critical to the process.

J Med Vet Mycol, 1992, 30(6), 443 - 50
Iron assimilation in Cryptococcus neoformans; Jacobson ES et al.; We studied the effects of iron chelators and of a thallium salt on growth of Cryptococcus neoformans in defined medium . An oxidant-sensitive mutant strain was found to require exogenous ferric iron for growth . Using this strain, we found that the synthetic iron chelator, N-hydroxyethylenediamine triacetate (HEDTA), in several saturation states, stimulated growth as well as the comparably saturated siderophore deferoxamine . This non-specific result makes the existence of a cryptococcal ferrihydroxamate receptor doubtful . The catechols, caffeic acid, L-3, 4-dihydroxyphenylalanine, epinephrine, gallic acid, 3-hydroxytyramine (dopamine) and norepinephrine, were tested for growth stimulation in iron deprivation, under conditions in which deferoxamine was stimulatory . Catechols were found to be either neutral or inhibitory . The ferrous iron chelator, bathophenanthroline disulfonate (BPDS), inhibited growth strongly in the absence of exogenous iron, suggesting that ferric ion must be reduced before it can be internalized . Direct evidence of extracellular reduction was provided by accumulation of red-coloured ferrous-BPDS complex . The inhibition caused by BPDS was relieved by ferric HEDTA, even in the presence of 10-fold increased BPDS, suggesting a second, low-affinity, non-reductive iron uptake pathway . This inference was further supported by the observation that toxicity of the non-reducible ferric analogue, thallium (III), is relieved by iron repletion.

Chemotherapy, 1992, 38(5), 297 - 302
In vitro activity of amphotericin B, hamycin and their novel water-soluble compounds against pathogenic yeasts; Sekhon AS et al.; Twenty-eight pathogenic isolates, 4 each of Candida albicans, C . lusitaniae, C . parapsilosis, Cryptococcus neoformans, Torulopsis glabrata and Trichosporon beigelii were tested for their in vitro sensitivity to amphotericin B (AmB), hamycin (HA) and their novel water-soluble compounds, namely JAI-AmB (oral and injectable; patents pending) and JAI-HA (Jaimycin Inc., Walnut Creek, Calif., USA), using a standard double-dilution broth (1 ml/tube) procedure . The 2 novel compounds, namely JAI-AmB and JAI-HA, contain one twenty-fifth (w/w) of the AmB and HA, respectively . Results showed that the minimal inhibitory concentrations (MICs) of AmB for all species, except C . lusitaniae and Tr . beigelii (3.125-6.25 micrograms/ml), were 0.195-1.56 micrograms/ml . The values of JAI-AmB (oral) for C . albicans, C . parapsilosis, Cr . neoformans and To . glabrata ranged from 0.78 to 25 micrograms/ml . The MICs of JAI-AmB (oral) for the other yeasts were 100 micrograms/ml . All of the yeasts yielded higher MICs (3.125-100 micrograms/ml) against JAI-AmB (injectable) than the JAI-AmB (oral) preparation . Except for C . parapsilosis (MICs 25-100 micrograms/ml), all of the other species showed greater sensitivity to the parent HA (0.195-100 micrograms/ml) than AmB . The values for JAI-HA ranged from 0.195 to 100 micrograms/ml for all isolates, except C . tropicalis (100 micrograms/ml) . Based on our in vitro findings, in vivo efficacies of JAI-AmB and JAI-HA should be carried out.

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