Cryptococci

Arch Pathol Lab Med, 1990 Sep, 114(9), 923 - 5
Cumulative positivity rates of multiple blood cultures for Mycobacterium avium-intracellulare and Cryptococcus neoformans in patients with the acquired immunodeficiency syndrome; Yagupsky P et al.; We examined the occurrence of low-grade Mycobacterium avium-intracellulare bacteremia and Cryptococcus neoformans fungemia in patients with the acquired immunodeficiency syndrome and the consistency of positive cultures obtained using a sensitive blood culture system (Isolator, E . I . Du Pont de Nemours, Wilmington, Del) for the recovery of these organisms . The blood culture records were reviewed, and the proportion of positive blood cultures yielding less than 1 colony-forming unit per milliliter of M avium-intracellulare or C neoformans was calculated . To determine consistency, a period of potentially detectable septicemia was defined as the period between 1 week before the first positive blood culture and the last positive blood culture, providing consecutive positive blood cultures were separated by less than 2 weeks . All positive and negative blood cultures obtained during the period of potentially detectable septicemia were considered in the data analysis . Overall, 40 (16.9%) of 236 cultures positive for M avium-intracellulare and 36 (57.1%) of 63 for C neoformans yielded less than 1 colony-forming unit per milliliter . Mycobacteremia was detected in 52 of 57 periods of potentially detectable septicemia in the first culture and in 56 of 57 in the first two (cumulative detection rates of 91.2% and 98.2%, respectively) . Cryptococcemia was detected in 12 of 17 periods of potentially detectable septicemia in the first culture and in 15 of 17 in the first two (cumulative detection rates of 70.6% and 88.2%, respectively) . Because of the sensitivity of the blood culture system and the consistency of M avium-intracellulare bacteremia and C neoformans fungemia in patients with the acquired immunodeficiency syndrome, it appears that two blood cultures are sufficient for the detection of most septic episodes caused by these organisms.

Mol Cell Biol, 1990 Sep, 10(9), 4538 - 44
Isolation of the URA5 gene from Cryptococcus neoformans var . neoformans and its use as a selective marker for transformation; Edman JC et al.; A cDNA encoding Cryptococcus neoformans orotidine monophosphate pyrophosphorylase (OMPPase) has been isolated by complementation of the cognate Escherichia coli pyrE mutant . The cDNA was used as a probe to isolate a genomic DNA fragment encoding the OMPPase gene (URA5) . By using electroporation for the introduction of plasmid DNA containing the URA5 gene, C . neoformans ura5 mutants could be transformed at low efficiency . Ura+ transformants obtained with supercoiled plasmids containing the URA5 gene showed marked mitotic instability and contained extrachromosomal URA5 sequences, suggesting limited ability to replicate within C . neoformans . Transformants obtained with linear DNA were of two classes: stable transformants with integrated URA5 sequences, and unstable transformants with extrachromosomal URA5 sequences.

J Antimicrob Chemother, 1990 Sep, 26(3), 387 - 97
The pharmacokinetics of BAY R3783 and its efficacy in the treatment of experimental cryptococcal meningitis; Wright KA et al.; We studied the pharmacokinetics and efficacy of BAY R3783, a new antifungal azole compound, in rabbits and compared it with fluconazole and itraconazole . BAY R3783 has at least two active metabolites, BAY U3624 and BAY U3625 . We measured serum concentrations of all three compounds; the peak serum level for the parent compound was approximately two hours post dose . BAY R3783 and its metabolites also crossed the blood-CSF barrier; the mean CSF level of BAY R3783 was 30.5% of simultaneous serum levels . The in-vivo activity of the azoles was compared in a model of cryptococcal meningitis in immunosuppressed rabbits . BAY R3783, fluconazole and itraconazole all reduced yeast counts in the CSF with equal efficacy over ten days of therapy at 100 mg/day . In this model, BAY R3783 was effective in the treatment of cryptococcal meningitis.

J Am Acad Dermatol, 1990 Sep, 23(3 Pt 2), 602 - 7
Itraconazole in opportunistic mycoses: cryptococcosis and aspergillosis; Denning DW et al.; Striking results were obtained with oral itraconazole therapy in two opportunistic mycoses . Of 28 patients with cryptococcal meningitis, 18 achieved complete responses, including 16 of 24 patients with acquired immunodeficiency syndrome . Other manifestations of cryptococcosis were similarly responsive . In aspergillosis 12 of 15 patients responded, including 8 of 10 immunocompromised hosts . These patients included those with invasive pulmonary disease (4/5), skeletal disease (2/2), pleural disease (1/2), and pericardial, sinus, mastoid, hepatosplenic, or nail disease (1/1) . These results with itraconazole compare favorably to conventional (parenteral) therapy, and toxicity was minimal . This suggests that comparative trials are now in order.

J Am Acad Dermatol, 1990 Sep, 23(3 Pt 2), 587 - 93
European experience with itraconazole in systemic mycoses; Viviani MA et al.; Since January 1985 more than 100 patients with deep fungal infections have been treated with itraconazole (200 to 400 mg/day) in Northern Italy . Evaluation of the drug efficacy and tolerance was possible in one patient with sporotrichosis, in 34 with aspergillosis, and in 36 with cryptococcosis (mainly patients positive for human immunodeficiency virus) . Response to itraconazole alone was obtained in the case of sporotrichosis and in 24 of 34 patients with different forms of aspergillosis (of the 18 patients with invasive pulmonary aspergillosis, 15 were cured) . Patients with cryptococcosis received itraconazole for active infection and/or for prevention of relapse . Active infection was treated successfully with itraconazole alone in 9 of 12 patients and with itraconazole plus flucytosine in 8 of 10 patients . Of the 31 patients who received itraconazole maintenance therapy for up to 27 months, 4 (13%) had relapses; 14 (45%) did not have relapses, and decline of serum antigen was detected in 12 of them; and 13 (42%) were completely cured (serum antigen titer dropped to zero) . With the exception of hypokalemia in one patient, itraconazole was well tolerated even in patients who received the drug for several months or years.

J Clin Neuroophthalmol, 1990 Sep, 10(3), 167 - 74
Neuro-ophthalmic findings in acquired immunodeficiency syndrome; Mansour AM; We reviewed the neuro-ophthalmic findings in 177 subjects with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex who underwent an eye examination in one center from January 1984 to May 1989 . The findings included ocular motor nerve palsies (five cases), papilledema (two cases), cytomegalovirus optic neuritis (two cases), cortical blindness (one case), conjugate gaze palsy (one case), and altitudinal visual field defect (one case) . These findings were attributed to central nervous system toxoplasmosis (four cases) or lymphoma (one case), cryptococcal meningitis (two cases), systemic cytomegalovirus infections (two cases), and herpes simplex encephalitis (one case) . Of 177 patients, 61 patients were tested for syphilis . Twenty-six patients had positive rapid plasma reagin titers, and 28 had positive fluorescent treponemal antibody-absorbed tests . Human immunodeficiency virus-infected individuals need to be screened routinely for syphilis.

Am J Vet Res, 1990 Sep, 51(9), 1454 - 8
Evaluation of ketoconazole and itraconazole for treatment of disseminated cryptococcosis in cats; Medleau L et al.; During the first part of a study, cats were inoculated with Cryptococcus neoformans via the following routes: intradermal, intranasal, IV, and intracisternal . Only use of the IV route of inoculation consistently induced disseminated cryptococcosis . In the second part of the study, disseminated cryptococcosis was experimentally induced in cats via IV inoculation of C neoformans . One month after inoculation, 3 cats were treated with ketoconazole (10 mg/kg of body weight/d) and 3 cats were treated with itraconazole (10 mg/kg/d) for 3 months . One of the ketoconazole-treated and 2 of the itraconazole-treated cats also had cryptococcosis of the CNS when treatment was begun . During treatment, serum cryptococcal antigen titer progressively decreased in all cats . Abnormalities in CBC values or the serum biochemical profile were not found in any cat during treatment . However, all ketoconazole-treated cats became anorectic and lost weight . Side effects were not seen in itraconazole-treated cats . During the 3-month posttreatment observation period, all cats remained healthy . At necropsy, histologic evidence of cryptococcosis was not found in the 3 ketoconazole-treated cats or in 2 of the itraconazole-treated cats . In the third itraconazole-treated cat, cryptococcal organisms were found in the kidneys.

J Infect Dis, 1990 Sep, 162(3), 727 - 30
Azoles and AIDS; Larsen RA; The treatment of opportunistic infections in AIDS patients is changing rapidly as new drugs become available and new studies of old drugs are completed . I have tried to use the AIDS commentaries to keep up with these advances . Since fluconazole has just recently been approved by the US Food and Drug Administration, I asked Dr . Robert A . Larsen, an active clinical investigator at the University of Southern California School of Medicine, to review his current recommendations for the use of the azoles in AIDS patients . The response to therapy of the various mycoses in patients with advanced human immunodeficiency virus (HIV) infection is dramatically different from that in other patient populations and has different end points in each group . Cure is uncommon in HIV-infected patients, and relapsing infection when antifungal therapy is stopped is the rule . Control of infection with relief of symptoms and return to productive, high-quality life is therefore a commendable goal and a reasonable end point . Thus, the azoles, especially fluconazole, are important additions . From the data presented here it appears that amphotericin may still have an edge over fluconazole for acute therapy of cryptococcal meningitis in sicker patients, at least for the first several weeks (although fluconazole may be as good and is certainly less toxic and easier to administer for patients who can take oral medications) . Whether 5FC should be added when amphotericin is used for acute therapy is still controversial . Dr . Larsen appears to favor it while my group feels that the potentiation of bone marrow toxicity without any clear evidence of enhanced efficacy in AIDS patients argues against its use.(ABSTRACT TRUNCATED AT 250 WORDS)

Indian J Pediatr, 1990 Sep-Oct, 57(5), 685 - 91
Sub acute and chronic meningitis in children--an immunological study of cerebrospinal fluid; Chandramuki A et al.; Cerebrospinal fluid (CSF) from 274 cases of subacute to chronic meningitis in age groups from 3 months to 12 years were analysed for the presence of antibody response to mycobacterial and cysticercal antigens by enzyme linked immunosorbent assay (ELISA) . Simultaneously other correlative parameters such as CSF cell cytology by cytospin studies, mycobacterial antigens of Lipoarabinomannan (LAM) type (a polysaccharide antigen) by reverse passive haemagglutination assay (RPHA) CSF C-reactive protein (CRP) by latex agglutination and microbial cultures for mycobacterium tuberculosis and fungi were carried out . Antimycobacterial antibody was present in 35.4% of the cases . In 57.66% of the cases there was no demonstrable immune response to either mycobacterial or cysticercal antigens . However, it was interesting to note that 5.47% of the cases revealed the presence of anticysticercal antibody in the CSF . The mycobacterial antigen (LAM polysaccharide antigen) was found in 72.6% of the cases . There was no evidence of carcinomatous or cryptococcal meningitis . This study stresses the role of multimodal diagnostic tests on CSF for investigating cases of chronic and subacute meningitis irrespective of leading clues such as tuberculosis.

Infect Immun, 1990 Sep, 58(9), 2919 - 22
Catecholamines and virulence of Cryptococcus neoformans; Polacheck I et al.; Cryptococcus neoformans was unable to utilize catecholamines (epinephrine, norepinephrine, or dopamine) as sole carbon or nitrogen sources . Therefore, catecholamines are not essential growth factors for this fungus and the brain is not a preferred nutritional niche for its growth with regard to catecholamines . To establish whether the brain is a survival niche for C . neoformans and to explain the role of phenoloxidase as a virulence factor, a wild-type strain that had phenoloxidase activity and mutants which lacked it were exposed to an epinephrine oxidative system, and the survival of both strains was tested . The oxidative system contained epinephrine as an electron donor, Fe3+ as the catalytic transition metal ion, and hydrogen peroxide as an electron acceptor . The wild-type strain was found to be resistant to this oxidative system, whereas under the same conditions the mutant strain was susceptible and its survival decreased at a rate of 4 logs per h . Damage to high-molecular-weight DNA seems to be a causative factor of cell death after exposure of the mutants to the oxidative system . These results suggest that C . neoformans may survive in the brain because of its ability to utilize catecholamines for melanogenesis and thus neutralize the harmful effects of catecholamines which are manifested in the presence of hydrogen peroxide and transition metal ions . The role of phenoloxidase in resistance to the epinephrine oxidative system is also discussed.

Mycoses, 1990 Sep-Oct, 33(9-10), 465 - 7
Isolation of Cryptococcus neoformans var . neoformans from canine otitis; Pal M et al.; Cryptococcus neoformans was demonstrated in the clinical material of a 15-year-old male dog with a history of chronic otitis externa by employing Helianthus annuus seed agar as a selective medium . The examination of the isolate for sexual compatibility on modified Helianthus annuus seed medium revealed that it belonged to Filobasidiella neoformans var . neoformans 'alpha' mating type . In the authors' view, this appears to be the first report of isolation of Cr . neoformans var . neoformans from diseased ear of a dog.

Br J Clin Pract Suppl, 1990 Sep, 71, 11 - 22
Fungal infections in AIDS patients; Stevens DA; The mycoses are of increasing importance because of the AIDS epidemic . Oral and other forms of candidosis are nearly universal in AIDS patients . Cryptococcosis is the most common lethal mycosis, and may number tens of thousands of cases in AIDS worldwide annually . As the number of AIDS patients mounts, a rising tide of infections due to nearly all recognised fungal pathogens is occurring; examples include histoplasmosis, coccidioidomycosis and penicilliosis . These experiences have led to an investigation of new drugs which are compatible with the understanding that AIDS patients presently have an incurable underlying disease; that is, the drugs would be oral (allowing outpatient management) and/or have low toxicity, and may still be useful if only as a suppressive . These investigations have thus far focused on the triazoles . The current status of the mycoses and AIDS is reviewed.

Mycoses, 1990 Sep-Oct, 33(9-10), 455 - 63
Localized cutaneous cryptococcosis successfully treated with itraconazole . Review of medication in 18 cases reported in Japan; Sato T et al.; A case of localized cutaneous cryptococcosis successfully treated with oral itraconazole is reported . The patient, a 63-year-old Japanese housewife, had had an erythematous and partly eroded lesion in the area of her right earlobe for about 10 months . No findings suggesting a primary focus of Cryptococcus infection were found in the lung, central nervous system or other internal organs . The isolate obtained from the lesion was identified as Cryptococcus neoformans based on the demonstration of encapsulated blastospores and its biological characteristics . The clinical course shifted toward healing in parallel with a decreased serum level of anticryptococcal antibody after initiation of treatment with oral itraconazole in a dose of 100 mg once daily . The treatment was discontinued after 13 weeks . There were neither subjective nor objective side effects . Furthermore, this paper reviews the medications employed in 18 cases with cutaneous cryptococcosis reported in Japan during the nearly 40-year period between 1952 and 1989.

Br J Clin Pract Suppl, 1990 Sep, 71, 32 - 40
Oral and parenteral treatment with itraconazole in various superficial and systemic experimental fungal infections . Comparisons with other antifungals and combination therapy; Van Cutsem J; Itraconazole has been tested in vitro against 6,113 different strains of a total of 252 fungal species . Almost all medically important fungi are apparently sensitive to itraconazole . Topical and oral treatment with itraconazole was found to be successful in microsporosis, trichophytosis, vulvovaginal, gastrointestinal and systemic candidosis, pityrosporosis, sporotrichosis, histoplasmosis, aspergillosis and cryptococcosis induced in a number of animal models . Vulvovaginal candidosis responded well to itraconazole, with a one-day topical or oral treatment resulting in a complete cure . The same results could not be achieved with the same concentration or dosage of either ketoconazole or fluconazole . Biologically active antifungal levels were present in plasma and vaginal fluid of rats after one dose of itraconazole 10 mg/kg for at least 72 hours . Itraconazole was also found to be successful in immunodepressed animals infected with a number of different diseases and in disseminated and systemic infections, such as candidosis, aspergillosis and cryptococcosis . Oral and parenteral itraconazole treatment was compared with oral and parenteral fluconazole treatment and parenteral amphotericin B in a number of models . Results overall were better with itraconazole . Combination therapy of itraconazole with fluconazole was not found to be superior to treatment with itraconazole alone . No side-effects were observed with itraconazole treatment.

Arch Otolaryngol Head Neck Surg, 1990 Aug, 116(8), 962 - 4
Reversible hearing loss in a patient with cryptococcosis; Mayer JM et al.; A 16-year-old girl had hearing loss, paroxysmal tremor, gait disorders, and psychiatric disturbances as the initial manifestations of a cryptococcal meningoencephalitis . Imaging demonstrated an obstructive hydrocephalus, and neuro-otological explorations showed a retrocochlear deafness and diffuse brainstem involvement . Emphasis is on the deafness, which rarely occurs as a presenting symptom in this condition, and on its dramatic improvement following antimycotic therapy.

J Bacteriol, 1990 Aug, 172(8), 4238 - 46
Rapid genetic identification and mapping of enzymatically amplified ribosomal DNA from several Cryptococcus species; Vilgalys R et al.; Detailed restriction analyses of many samples often require substantial amounts of time and effort for DNA extraction, restriction digests, Southern blotting, and hybridization . We describe a novel approach that uses the polymerase chain reaction (PCR) for rapid simplified restriction typing and mapping of DNA from many different isolates . DNA fragments up to 2 kilobase pairs in length were efficiently amplified from crude DNA samples of several pathogenic Cryptococcus species, including C . neoformans, C . albidus, C . laurentii, and C . uniguttulatus . Digestion and electrophoresis of the PCR products by using frequent-cutting restriction enzymes produced complex restriction phenotypes (fingerprints) that were often unique for each strain or species . We used the PCR to amplify and analyze restriction pattern variation within three major portions of the ribosomal DNA (rDNA) repeats from these fungi . Detailed mapping of many restriction sites within the rDNA locus was determined by fingerprint analysis of progressively larger PCR fragments sharing a common primer site at one end . As judged by PCR fingerprints, the rDNA of 19 C . neoformans isolates showed no variation for four restriction enzymes that we surveyed . Other Cryptococcus spp . showed varying levels of restriction pattern variation within their rDNAs and were shown to be genetically distinct from C . neoformans . The PCR primers used in this study have also been successfully applied for amplification of rDNAs from other pathogenic and nonpathogenic fungi, including Candida spp., and ought to have wide applicability for clinical detection and other studies.

Antonie Van Leeuwenhoek, 1990 Aug, 58(2), 107 - 14
Inhibition and killing of fungi by the polyamine oxidase-polyamine system . Antifungal activity of the PAO-polyamine system; Levitz SM et al.; Both components of the polyamine oxidase (PAO)-polyamine system are known to be present in phagocytes and have thus been postulated to contribute to the antimicrobial activity of these cells . Therefore, the effects of the PAO-polyamine system on three medically important opportunistic fungi were examined . Yeasts of Cryptococcus neoformans, but not Candida albicans blastoconidia or Aspergillus fumigatus conidia, were efficiently killed by the system . Two putative end products of the system, hydrogen peroxide and acrolein, both killed C . neoformans at concentrations attainable with the whole system . However, catalase failed to inhibit activity of the whole system, making hydrogen peroxide an unlikely mediator of killing . Although C . albicans blastoconidia and A . fumigatus conidia were not killed by the PAO-polyamine system, germ tube formation by the former, and hyphal growth by the latter, were markedly inhibited . These data establish that the PAO-polyamine system possesses antifungal activity.

Acta Neurol (Napoli), 1990 Aug, 12(4), 301 - 4
A case of cryptococcal meningoencephalitis and focal cerebral vasculitis with transient immunodeficiency; Scalzini A et al.; The AA . report a case of CNS cryptococcosis with vasculopathic complications in a woman in perfect physical conditions . The patient was admitted to hospital after complaining for 20 days of fever, headache and rachialgia . CSF examination revealed hypoglicorrachia (18 mg %), cells 440 mmc (polymorphonuclear leukocytes 90%), brain CT scan negative . During antimycobacterial treatment right hemiparesis appeared; brain CT: hypodense lesion in the posterior brachium of the left inner capsule; at its base the lesion showed a hypodense streak coherent with thromboembolic damage or deep vasculitis . OKT4 lymphocytes were 6% (absolute number: 70) . The antimycotic treatment, following the positive reaction of the CSF culture to Cryptococcus Neoformans, entirely cured the hemiparesis and normalized the CSF while OKT4 lymphocytes rapidly grew.

Ann Intern Med, 1990 Aug 1, 113(3), 183 - 7
Fluconazole compared with amphotericin B plus flucytosine for cryptococcal meningitis in AIDS . A randomized trial; Larsen RA et al.; OBJECTIVE: To compare the efficacy of fluconazole with amphotericin B plus flucytosine in the treatment of cryptococcal meningitis . DESIGN: Patients were randomly assigned to oral fluconazole, 400 mg/d, for 10 weeks or to amphotericin B, 0.7 mg/kg body weight daily for 1 week, then three times weekly for 9 weeks combined with flucytosine, 150 mg/kg d, in four divided doses . SETTING: Los Angeles County-University of Southern California Medical Center . PATIENTS: Between 15 February and 7 December 1988, 42 patients had evidence of their first episode of cryptococcal meningitis, of whom 21 participated in the trial . All patients enrolled were men with the acquired immunodeficiency syndrome (AIDS) except one woman who was receiving prednisone therapy and was excluded from the final analysis . RESULTS: Of 14 patients with AIDS assigned to fluconazole, 8 (57%; 95% CI, 29% to 82%) failed; none of the 6 patients with AIDS failed who were assigned to amphotericin B plus flucytosine therapy (0%; CI, 0% to 46%) (Fisher exact test, P = 0.04) . The mean duration of positive cerebrospinal fluid cultures was 40.6 +/- 5.4 days in patients receiving fluconazole and 15.6 +/- 6.6 days in patients receiving amphotericin B plus flucytosine (Mann-Whitney test, P = 0.02) . Overall, 4 patients assigned to fluconazole therapy died whereas no patient assigned to amphotericin B plus flucytosine therapy died (Fisher exact test, P = 0.27) . CONCLUSION: Amphotericin B used in combination with flucytosine has superior mycologic and clinical efficacy compared with fluconazole for the treatment of cryptococcal meningitis in patients with AIDS.

J Gen Microbiol, 1990 Aug, 136 ( Pt 8), 1525 - 35
Immunochemical studies of Aspergillus fumigatus mycelial antigens by polyacrylamide gel electrophoresis and western blotting techniques; Hearn VM et al.; Differences were detectable among strains of the opportunist fungal pathogen Aspergillus fumigatus when water-soluble (WS) preparations were analysed by combined SDS-PAGE and Western blotting procedures . A wide range of molecules of apparent molecular masses from approximately 20 to greater than 100 kDa showed specific binding to antibodies raised in rabbits to A . fumigatus wall and cytoplasmic components . The ability to bind antibody was markedly reduced by treatment of these antigens with sodium periodate or with specific proteases or glucanases . Pretreatment of blotted antigens with either concanavalin A (ConA) or wheat germ agglutinin (WGA) did not, however, inhibit subsequent antibody binding . The antigens of subfractions prepared from a single strain of A . fumigatus WS material were also susceptible to periodate oxidation and enzymic hydrolysis . Slight cross-reactivity was apparent when crude preparations of cellular or culture filtrate antigens, used in this laboratory to detect antibodies to Candida albicans, Coccidioides immitis and Cryptococcus neoformans, were probed with hyperimmune rabbit antisera to A . fumigatus . Efforts were made to characterize the WS preparations of A . fumigatus, used as diagnostic antigens in many laboratories . The electrophoretically separated antigenic moieties were shown to be predominantly glycoproteins . Binding of cytoplasmic antigens to antibodies raised to wall material showed the presence of many common components in both wall and cytosol . Antiserum to wall components revealed most differentiation among A . fumigatus strains.

Chest, 1990 Jul, 98(1), 38 - 43
Complications of corticosteroid therapy in patients with the acquired immunodeficiency syndrome and Pneumocystis carinii pneumonia; Lambertus MW et al.; We retrospectively studied the acute toxicity of corticosteroid therapy in 23 episodes of PCP occurring in the setting of AIDS and determined the incidence of HIV-related complications following these and 16 other contemporaneous episodes of AIDS-related PCP treated with antimicrobials alone . The mean duration of corticosteroid therapy was 5.4 days and the mean total dose was 660 mg of methylprednisolone . Cryptococcus neoformans and Listeria monocytogenes infection each occurred once within one month of therapy in corticosteroid-treated patients; no other noteworthy acute corticosteroid toxicity was noted . Since all patients with imminently lethal PCP received corticosteroids, we could not assess the effect of these agents on acute mortality . After six months the rates of new AIDS-related diagnoses and of post-hospitalization mortality were equivalent in the two groups . We also have critically reviewed the available literature regarding this use of corticosteroids.

Appl Environ Microbiol, 1990 Jul, 56(7), 2219 - 22
Application of the theory of adaptive polymorphism to the ecology and epidemiology of pathogenic yeasts; Hunter PR et al.; The theory of adaptive polymorphism predicts that species occupying broad ecological niches will be phenotypically and genotypically more varied than those occupying narrow niches . It is suggested that this theory has direct relevance to the epidemiology of microbial pathogens in that environmental pathogens inhabit a broader niche and should be expected to exhibit greater variation than pathogens that are obligate commensals . This proved to be the case when one obligate commensal, the pathogenic yeast Candida albicans, was compared with other Candida spp . and an environmental pathogen, Cryptococcus neoformans . Further evidence of this relationship is derived from the literature . This observation adds further support to the theory of adaptive polymorphism, although the mechanisms of maintenance of polymorphism is asexually reproducing populations must be different from those in sexually reproducing populations . This observation may give important clues to the epidemiology of those infections for which it is not already known.

Rev Infect Dis, 1990 Jul-Aug, 12 Suppl 5, S561 - 9
Considerations for the evaluation of antiretroviral agents in infants and children infected with human immunodeficiency virus: a perspective from the National Cancer Institute; Pizzo PA; Human immunodeficiency virus (HIV) infection in infants and young children differs in a number of ways from that in adults . In most HIV-infected children the infection is acquired perinatally and the course of infection is more accelerated than in adults . Diseases related to B cell defects and dysgammaglobulinemia (e.g., multiple or recurrent bacterial infections) predominate early in the disease, and children can be symptomatic before their CD4+ count decreases . Lymphoid interstitial pneumonitis occurs frequently and almost exclusively in children, and a number of the opportunistic infections (e.g., cryptococcosis, toxoplasmosis) or malignancies (e.g., Kaposi's sarcoma) occur infrequently in children . A major disease manifestation in the pediatric population is HIV encephalopathy, which results in impairment in neurologic development that can lead to loss or lack of developmental milestones and to diminished intellectual function . The methodology and design of clinical trials for the study of pediatric HIV infection should consider these clinical and laboratory manifestations as well as the developmental differences that reflect the disease in infants and young children.

J Clin Microbiol, 1990 Jul, 28(7), 1642 - 4
Natural habitat of Cryptococcus neoformans var . gattii; Ellis DH et al.; Environmental isolations have established that Cryptococcus neoformans var . gattii appears to have a specific ecological association with Eucalyptus camaldulensis . So far, we have isolated C . neoformans var . gattii on 35 separate occasions, all from samples associated with E . camaldulensis . The global distribution of E . camaldulensis appears to correspond to the epidemiologic distribution of cryptococcosis caused by C . neoformans var . gattii . No other environmental source for the fungus has yet been detected, and no other eucalypt has the distribution pattern corresponding to reported cases caused by this fungus . These findings may provided an explanation for the high incidence of infections caused by C . neoformans var . gattii in Australian aborigines living in the Northern Territory and for its low worldwide incidence in acquired immunodeficiency syndrome patients.

Infect Immun, 1990 Jul, 58(7), 2115 - 9
Opsonic activity of cerebrospinal fluid in experimental cryptococcal meningitis; Hobbs MM et al.; The role of antibody in protection against infection with Cryptococcus neoformans is undefined . In this paper we describe the development of opsonic activity in the cerebrospinal fluid (CSF) of rabbits in response to cryptococcal meningitis . The opsonin appeared to be immunoglobulin G (IgG); the activity was heat stable, copurified with the IgG fraction during protein A separation, and could be absorbed by encapsulated cryptococci . Immunosuppression with cyclosporine could be administered to prevent or allow in vivo deposition of IgG on the polysaccharide capsule of yeast in the CSF . Both early and late cyclosporine regimens resulted in prolonged, severe meningeal infections corresponding to the complete absence of in vitro opsonic activity in the CSF . While the production of opsonic antibody is part of the successful host response against C . neoformans in the central nervous system of rabbits, the presence of specific immunoglobulin by itself is insufficient for complete protection.

Infect Immun, 1990 Jul, 58(7), 2085 - 90
Cryptococcus neoformans, Candida albicans, and other fungi bind specifically to the glycosphingolipid lactosylceramide (Gal beta 1-4Glc beta 1-1Cer), a possible adhesion receptor for yeasts; Jimenez-Lucho V et al.; The role of glycosphingolipids as adhesion receptors for yeasts was examined . Cryptococcus neoformans, Candida albicans, and Saccharomyces cerevisiae, as well as Histoplasma capsulatum and Sporotrichum schenckii (in their yeast phases), bound specifically to lactosylceramide (Gal beta 1-4Glc beta 1-1Cer), as measured by overlaying glycosphingolipid chromatograms with 125I-labeled organisms . An unsubstituted galactosyl residue was required for binding, because the yeasts did not bind to glucosylceramide (Glc beta 1-1Cer) derived from lactosylceramide by treatment with beta-galactosidase or to other neutral or acidic glycosphingolipids tested that contained internal lactosyl residues . Interestingly, the yeasts preferentially bound to the upper band of the lactosylceramide doublet in human lung and bovine erythrocytes, suggesting that the ceramide structure also affects binding . Active metabolism of the yeasts was required for binding to lactosylceramide, as binding was maximal in buffer containing glucose and was almost completely abolished in nutrient-deficient medium . C . neoformans also bound to human glioma brain cells grown in monolayers, and this binding was inhibited by liposomes containing lactosylceramide but not by liposomes containing glucosylceramide . Lactosylceramide is a major glycosphingolipid in these cells and the only one to which the yeasts bound . As lactosylceramide is widely distributed in epithelial tissues, this glycosphingolipid may be the receptor for yeast colonization and disseminated disease in humans.

J Leukoc Biol, 1990 Jul, 48(1), 15 - 26
Cytoplasmic components of natural killer cells limit the growth of Cryptococcus neoformans; Hidore MR et al.; Murine natural killer (NK) cell-mediated inhibition of growth of a yeast-like target cell, Cryptococcus neoformans, was completely abrogated by blocking the effector cell secretory process with monensin . Therefore, further studies were performed to determine the ability of various cytoplasmic fractions of NK cells to mediate inhibition of cryptococcal growth . Percoll-fractionated homogenates of rat LGL tumor cells demonstrated that the granule-containing fractions plus three additional sets of less dense cytoplasmic fractions displayed anti-cryptococcal activity; whereas only the cytoplasmic granule-containing fractions had cytotoxic activity against YAC-1 tumor cell and sheep erythrocyte targets . Maximal cryptococcal growth inhibition induced by LGL granules occurred after a 1 h incubation, required the presence of Ca2+ (1.0 mM) or Mg2+ (0.5 mM or 5.0 mM), and was completely abrogated in the presence of rabbit anti-LGL granule IgG . Cytolysin, the granule component which mediates tumor cell and sheep erythrocyte lysis, effectively limited the growth of cryptococci . Since Percoll gradient fractionation of the LGL homogenates demonstrated three separate peaks of anti-cryptococcal activity other than the granule peak, it is possible that the cytolysin-containing granules are not the only subcellular component of NK cells playing a role in inhibition of C . neoformans growth.

J Antibiot (Tokyo), 1990 Jul, 43(7), 763 - 70
Pradimicins A, B and C: new antifungal antibiotics . II . In vitro and in vivo biological activities; Oki T et al.; Pradimicins A, B and C specify novel antibiotics produced by Actinomadura hibisca No . P157-2 (ATCC 53557) possessing potent and broad antifungal activity in vivo . They showed moderate in vitro antifungal activity against a wide variety of fungi and yeasts including clinically important pathogens, and were highly effective in systemic infection with Candida albicans in mice after iv and im administrations . Pradimicin A showed in vivo therapeutic activity against C . albicans, Cryptococcus neoformans and Aspergillus fumigatus in both normal and immunocompromized mice . 5-Fluorocytosine- and azole-resistant C . albicans strains were susceptible to pradimicin A . This antibiotic also demonstrated therapeutic efficacy against lung candidiasis and aspergillosis, vaginal candidiasis and skin Trichophyton mentagrophytes infection in mice with iv or topical treatment . The LD50 values after a single iv or im administration were 120 mg/kg and more than 400 mg/kg, respectively . Against various cultured mammalian cells, pradimicin A was noncytotoxic at 100 or 500 micrograms/ml, and showed potent anti-influenza virus activity with an IC50 value of 6.8 micrograms/ml.

Chest, 1990 Jul, 98(1), 24 - 8
Bronchoscopy specimens in adults with AIDS . Comparative yields of cytology, histology and culture for diagnosis of infectious agents; Weldon-Linne CM et al.; Bronchoscopy specimens from 183 known/suspected acquired immunodeficiency syndrome patients were evaluated for pathogens . In each case, transbronchial biopsies were evaluated and bronchoalveolar lavage material was cultured for viruses, fungi and mycobacteria and examined cytologically . A specimen was considered positive for a pathogen if detected by any one of the methods (TBB or BALC or culture) . BALC was more sensitive for Pneumocystis carinii than TBB (90 of 92 vs 67 of 80 cases) . TBB and BALC had poor sensitivities for cytomegalovirus detection (six of 79 and ten of 91 cases, respectively): 80 of 91 CMV cases were detected by culture only . Nineteen of 26 MB cases were positive by culture only: BALC and TBB detected only three of 26 and five of 23 cases, respectively . Three cryptococcosis cases were detected by culture only . One coccidioidomycosis case was positive by BALC and culture . Culture and BALC in combination detected 212 of 216 all significant pathogens . We believe that TBB is not routinely necessary in AIDS-related bronchoscopies in the absence of suspicion of neoplasia.

Mycoses, 1990 Jul-Aug, 33(7-8), 359 - 67
Cerebrospinal fluid indices in cryptococcal and tuberculous meningitis: the spider web coagulum and its diagnostic significance; Staib F et al.; The differentiation between a chronic cryptococcal meningitis and a chronic tuberculous meningitis may cause problems for the clinician only if standard microbiological methods are not applied to the diagnosis of both infections . In a male non-AIDS patient (50 y), 11 years after a suggested diagnosis of "tuberculous meningitis", meningoencephalitis with hydrocephalus was diagnosed and treated accordingly without success . Mycobacterium tuberculosis was never found . Because fibrin fibres of a spider web coagulum in the CSF resembled Aspergillus mycelium, the patient was then treated with amphotericin B + flucytosine . Finally, a mycological examination led to the true diagnosis: (1) In the CSF, resembling Aspergillus hyphae were found to be spider web coagulum fibres . (2) Cryptococcal meningoencephalitis based on the detection of Cryptococcus neoformans in CSF and its antigen in serum and CSF . - At post-mortem, cryptococcal meningoencephalitis was established as cause of death . Residual signs of tuberculosis could not be detected in the brain and the meninges . Common clinical similarities of cryptococcal and tuberculous meningitis and the possibility of a double infection are discussed . A comparison of the presence of Cr . neoformans in the meninges of non-AIDS and AIDS patients is made . The formation of spider web coagulum in the CSF is discussed . Proposals for the diagnosis, therapy and prophylaxis of cryptococcal meningitis are made.

Pharmazie, 1990 Jul, 45(8), 618 - 20
{The antifungal action of polygalacic acid glycosides}; Bader G et al.; Triterpenoid glycosides obtained from Solidago virgaurea L . and Bellis perennis L . (Asteraceae) inhibit the growth of human-pathogenic yeasts (Candida and Cryptococcus species) . First results are given of the investigations on the mode of action and the relationships between structure and activity of these compounds . The intensity of growth inhibition is influenced particularly by the carbohydrate chains of the glycosides . Monodesmosidic as well as bisdesmosidic glycosides of polygalacic acid exert fungicidic effects.

Mycoses, 1990 Jul-Aug, 33(7-8), 369 - 73
Persistence of Cryptococcus neoformans in seminal fluid and urine under itraconazole treatment . The urogenital tract (prostate) as a niche for Cryptococcus neoformans; Staib F et al.; The open questions of the persistence of Cryptococcus neoformans in the urogenital tract under antimycotic treatment can be examined under optimal mycological-diagnostic conditions only . The example of a case of cryptococcosis in an AIDS patient diagnosed and treated with itraconazole in the early secondary stage of cryptococcosis is used to discuss the problems of the persistence of Cr . neoformans involvement in the urogenital tract (prostate) . Data from a ten-week follow-up study are presented and discussed . The observations made have shown that itraconazole is effective in all regions of the body, with the exception of the urogenital tract . In addition to clinical examinations, cases treated with itraconazole should be finally subjected to cultural examination of prostatic secretion and/or seminal fluid, to exclude the possible presence of a symptom-free involvement of the prostate by Cr . neoformans.

Ir Med J, 1990 Jun, 83(2), 50 - 3
The emerging AIDS epidemic in Ireland--clinicopathological findings in 23 early cases; O'Briain DS et al.; A longitudinal study with follow up to the end of 1989 was carried out on 23 patients with AIDS who had attended St . James's Hospital, Dublin, by the end of 1987 . Until then only 33 cases of AIDS had been reported in Ireland . The patients, all of whom had antibodies to human immunodeficiency virus (HIV), were predominantly male, young (mean age 31.3 years) and belonged about equally to three major risk groups: homosexuals, intravenous drug abusers (IVDA) and haemophiliacs . AIDS was diagnosed because of oesophageal candidiasis (8 cases), Kaposi's sarcoma (4), mycobacterial infection (4), pneumocystis carinii pneumonia (3), toxoplasmosis (2) or encephalopathy (2) . Malignant lymphoma and a variety of infections occurred in the course of illness, and neurological involvement developed in 11 patients (48%) . Mortality following diagnosis of AIDS was 39% at one year and 64% after two years . Autopsy in 10 of the 16 deaths contributed much to defining the extent and nature of the disease . The demographic pattern, risk group status, survival and range of complications were broadly similar to the pattern of AIDS as seen elsewhere in developed countries . However, compared to the profile of disease reported from the United States, oesophageal candidiasis (52%) and Mycobacterium tuberculosis (22%) were more prominent, pneumocystis carinii pneumonia (39%), Kaposi's sarcoma (22%) and Mycobacterium avium intracellulare (13%) were less frequent and cryptococcal infection was not identified . These regional variations in the frequency of the various complications and particularly the prominence of tuberculosis, probably reflect the interaction of the immunocompromised patient with the local environment and may have important diagnostic and therapeutic implications.

Muscle Nerve, 1990 Jun, 13(6), 508 - 15
Skeletal muscle pathology in AIDS: an autopsy study; Wrzolek MA et al.; A survey of skeletal muscle pathology in 92 autopsied cases of AIDS revealed microscopic alterations in 64 cases . There were 40 cases of disuse atrophy, 8 of denervation atrophy, 2 of cryptococcal myositis, 1 of Mycobacterium avium intracellulare (MAI) infection and 2 of necrotizing myopathy associated with hyperkalemia . A second group of cases with changes of unknown etiology was found . These were tentatively ascribed to the direct or indirect action of HIV . This category includes 8 cases of inflammatory myopathy, 8 of necrotizing myopathy in absence of a known etiological factor, 3 of extreme atrophy and 4 of "regenerating" myopathy.

J Clin Gastroenterol, 1990 Jun, 12(3), 295 - 7
Gastrointestinal, hepatic, and pancreatic involvement with Cryptococcus neoformans in AIDS; Bonacini M et al.; We describe three cases of acquired immunodeficiency syndrome (AIDS) complicated by disseminated cryptococcosis with gastrointestinal involvement . The stomach, duodenum, colon, pancreas, and liver showed invasion by the fungus . Although none of the patients had any symptoms attributable to Cryptococcus neoformans, we speculate that cryptococcal invasion of the liver and gastrointestinal tract may be a contributor to the morbidity in these immunocompromised patients.

Arch Neurol, 1990 Jun, 47(6), 640 - 2
Seizures in human immunodeficiency virus infection; Wong MC et al.; Among 630 patients with human immunodeficiency virus infection, 70 patients with new-onset seizures were studied . Generalized seizures occurred in 66 patients (94%): they occurred as the initial seizure in 56 patients (80%) and during follow-up in another 10 patients (14%) . Partial seizures (18 patients), status epilepticus (10 patients), and recurrent seizures (38 patients) were also noted . Identified processes included cerebral toxoplasmosis in 11 patients, cerebral lymphoma in 8, metabolic derangement in 8, cryptococcal meningitis in 7, and vascular infarction in 4 . In 32 patients (46%) seizures were not associated with identifiable brain lesions and were believed to result from human immunodeficiency virus cerebral infection . Phenytoin treatment was associated with adverse drug reactions in 16 of 62 patients who received it . Our results suggest that the majority of patients with human immunodeficiency virus and seizures do not have secondary focal brain lesions as the cause of the seizures and that human immunodeficiency virus infection alone can, and often does, cause seizures.

Radiology, 1990 Jun, 175(3), 725 - 8
Cryptococcal pulmonary infection in patients with AIDS: radiographic appearance; Miller WT Jr et al.; The clinical, laboratory, and radiographic findings in seven patients with acquired immunodeficiency syndrome (AIDS) and cryptococcal pulmonary infections were reviewed . The infection was most commonly seen on radiographs as lymphadenopathy, interstitial infiltrates, or both . Interstitial infiltrates were commonly nodular . Large nodules or alveolar infiltrates, the most common findings at presentation in both immunocompetent patients and immunocompromised patients without AIDS, were not present in our series . Isolated pleural effusion was seen as the only radiographic finding in one case . Meningitis was present in six of seven cases and was neurologically silent in five of six cases . Cryptococcal pneumonia in AIDS patients should prompt a search for neurologically silent cryptococcal meningitis.

Infect Immun, 1990 Jun, 58(6), 1919 - 23
Passive immunization against Cryptococcus neoformans with an isotype-switch family of monoclonal antibodies reactive with cryptococcal polysaccharide; Sanford JE et al.; The in vivo properties of an immunoglobulin isotype-switch family of monoclonal antibodies specific for the polysaccharide capsule of Cryptococcus neoformans were examined in a murine model of cryptococcosis . Subclass-switch variants were isolated by sequential sublining of an immunoglobulin G subclass 1 (IgG1)-secreting cell line . Antibodies of the IgG1, IgG2a, and IgG2b isotypes with identical reactivities with cryptococcal polysaccharide were prepared . The antibodies had the distinct biological properties associated with the heavy chains of each respective isotype . The antibodies were used prophylactically or therapeutically in an attempt to alter the course of cryptococcal infection in mice . Survival of mice and a tissue census of the numbers of viable cryptococci in the lung, spleen, and brain were used as indicators of efficacy . Passive immunization with the IgG2a and IgG2b antibodies effected a reduction in the numbers of cryptococci in lung and spleen . Passive immunization with the IgG1 antibody was markedly less effective . Passive immunization had little or no effect on the numbers of cryptococci in brain tissue, regardless of the immunoglobulin isotype . Despite apparent efficacy with regard to reduction in the numbers of yeast cells in the lung and spleen, the results showed no improvement in survival from murine cryptococcosis . Our results indicate that passive immunization produces a modest effect on the course of murine cryptococcosis in tissues other than brain . However, under the experimental conditions used, such treatment does not have a measurable impact on the ultimate outcome of the infection.

J S Afr Vet Assoc, 1990 Jun, 61(2), 71 - 6
Systemic cryptococcosis in a cat; Berry WL et al.; A three-year-old, castrated, male, domestic cat presented with an antibiotic-resistant rhinitis, generalised lymphadenopathy, and skin nodules distributed over the neck, thorax and abdomen . Cryptococcus neoformans was identified on cytology and histopathology specimens, and cultured from all the specimens submitted . The cat died without antimicrobial therapy being instituted . Systemic cryptococcosis was confirmed on necropsy . Lesions were found in the upper and lower respiratory tracts, skin, subcutis, skeletal musculature, lymph nodes, kidney, eye and brain . This report details a case of systemic cryptococcosis in a cat and gives a review of feline cryptococcosis.

Semin Respir Infect, 1990 Jun, 5(2), 138 - 45
Cryptococcal meningitis in the acquired immunodeficiency syndrome; Panther LA et al.; Cryptococcosis is the most common, deep-seated fungal infection in AIDS patients, and cryptococcal meningitis is the most frequently observed syndrome . AIDS patients with cryptococcal meningitis usually have an indolent presentation and nonspecific findings on physical examination . Routine laboratory tests are of little assistance in diagnosing cryptococcal meningitis . Cerebrospinal fluid (CSF) white blood cell counts tend to be low, and glucose and protein levels are nonspecific . Serum cryptococcal antigen (CRAG) is a sensitive test for cryptococcal meningitis, and CSF CRAG is usually also positive . Definitive diagnosis is made by culture of the CSF . Therapy of cryptococcal meningitis is changing to antifungal agents that are easy to administer as outpatient therapy . Amphotericin B continues to be the primary antifungal used in initial treatment of cryptococcal meningitis; addition of flucytosine is of no benefit . Recent data suggest oral fluconazole is effective as primary therapy, and may be superior to amphotericin B as maintenance therapy . Maintenance therapy decreases the incidence of relapse and increases survival.

Neth J Med, 1990 Jun, 36(5-6), 242 - 5
Cryptococcal meningo-encephalitis after prolonged corticosteroid therapy; Koeleman JG et al.; We present a case of a 69-yr-old woman who developed cryptococcal meningo-encephalitis after 9 yr of corticosteroid therapy . The diagnosis was made on an India ink preparation and positive culture of the cerebrospinal fluid sediment . NMR-imaging was a useful tool for detecting intracerebral localisation of the infection . The patient was successfully treated with amphotericin B and flucytosine for 6 wk and with itraconazole for another 8 wk.

Antimicrob Agents Chemother, 1990 Jun, 34(6), 980 - 4
In vivo efficacy of SM-8668 (Sch 39304), a new oral triazole antifungal agent; Tanio T et al.; SM-8668 (Sch 39304) is a new oral antifungal agent which we evaluated in comparison with fluconazole in various fungal infection models . The prophylactic effect of SM-8668 was excellent against systemic candidiasis, aspergillosis, and cryptococcosis in mice . The 50% effective dose for SM-8668 was assessed at 10 days after infection and was 0.18, 3.7, and 5.9 mg/kg (body weight), respectively, for the above-mentioned fungal diseases . Fluconazole was about four times less effective than SM-8668 against systemic candidiasis and was only slightly effective at doses of 80 and 25 mg/kg against systemic aspergilosis and cryptococcosis, respectively . SM-8668 was also about four to eight times more active than fluconazole against vaginal candidiasis in rats and against dermatophytic infection in guinea pigs . In addition, topical SM-8668 was as effective as topical miconazole or tioconazole against skin mycosis in guinea pigs . After oral administration, SM-8668 showed a maximum concentration in serum similar to that of fluconazole in both mice and rats, but the elimination half-life and area under the serum concentration-time curve for SM-8668 were twice those for fluconazole.

Drugs, 1990 Jun, 39(6), 877 - 916
Fluconazole . A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in superficial and systemic mycoses; Grant SM et al.; Fluconazole is a bis-triazole antifungal drug with novel pharmacokinetic properties (metabolic stability, relatively high water solubility) which contribute to its therapeutic activity . Clinical experience is limited to a relatively small number of mycoses and, as might be expected at this early stage of development, optimal dosage and duration of treatment for some serious mycoses is not yet established . Further study to evaluate higher dosages and to establish the efficacy of fluconazole relative to more established antifungal agents is required . In patients with oropharyngeal or oesophageal candidiasis, fluconazole produces rapid relief and eradicates the yeast in 50 to 90% of patients . Relapse of oral infection is common in chronically immunocompromised patients regardless of the antifungal used, and adequate primary therapy plus long term prophylaxis appears necessary in patients with AIDS . A single oral dose of fluconazole was comparable to standard topical azole therapy in women with acute vaginal candidiasis . Preliminary reports of success against deep-seated candidiasis are encouraging; moreover, experience in noncomparative clinical trials suggests that fluconazole 200 to 400mg once daily resolves infection in the majority of seriously ill patients . Clinical improvement has been reported in a few cases of pulmonary Aspergillus infection but the overall efficacy of conventional dosages of fluconazole in this mycosis has not been as impressive . Early experience in coccidioidosis, predominantly meningitis, suggests a beneficial clinical effect with oral fluconazole in this difficult to treat mycosis but relapse remains a problem . Fluconazole is a promising treatment of cryptococcal meningitis . The rate of clinical resolution and eradication of Cryptococcus neoformans from cerebrospinal fluid has been similar between fluconazole and amphotericin B treatment groups in comparative trials . Comparative trials of maintenance therapy indicate a similar low rate of relapse among patients given oral fluconazole once daily and intravenous amphotericin B once weekly . However, these results are preliminary and further study is required . Fluconazole has been well tolerated to date but wider clinical experience is needed, especially with regard to the rate occurrence of hepatotoxicity and exfoliative skin reactions . The promising clinical response of patients with various forms of candidiasis or cryptococcosis--together with convenient administration regimens--recommends fluconazole as a useful addition to currently available systemic antifungal therapies, in particular for the treatment of mycoses in patients with AIDS.

Infect Immun, 1990 Jun, 58(6), 1914 - 8
Opsonization of Cryptococcus neoformans by a family of isotype-switch variant antibodies specific for the capsular polysaccharide; Schlageter AM et al.; A family of immunoglobulin isotype-switch variants was isolated by sib selection from a murine hybridoma which produced an immunoglobulin G subclass 1 (IgG1) antibody specific for the capsular polysaccharide of Cryptococcus neoformans . Antibodies of the IgG1, IgG2a, and IgG2b isotypes had similar serotype specificity patterns in double immunodiffusion assays which used polysaccharides of the four cryptococcal serotypes as antigens . A quantitative difference in the ability of the isotypes to form a precipitate with the polysaccharide was observed in a double immunodiffusion assay and confirmed in a quantitative precipitin assay . The relative precipitating activity of the antibodies was IgG2a greater than IgG1 much greater than IgG2b . Analysis by enzyme-linked immunosorbent assay of the reactivity of the three isotypes with cryptococcal polysaccharide showed identical titers and slopes, suggesting that the variable region of the class-switch antibodies was unaltered . This system allowed us to examine the effect of the Fc portion of the antibody on opsonization of encapsulated cryptococci . Yeast cells were precoated with antibodies of each isotype and incubated with murine macrophages or cultured human monocytes . Antibodies of all three isotypes exhibited a dose-dependent opsonization for phagocytosis by both human and murine phagocytes . The relative opsonic activity of the antibodies was IgG2a greater than IgG1 greater than IgG2b.

Chest, 1990 Jun, 97(6), 1349 - 55
Detection of fungi and other pathogens in immunocompromised patients by bronchoalveolar lavage in an area endemic for coccidioidomycosis; Sobonya RE et al.; Bronchoalveolar lavage (BAL) was performed in 51 adult immunocompromised patients (30 acquired immunodeficiency syndrome {AIDS} and 21 non-AIDS) as part of an extensive diagnostic evaluation for diffuse pulmonary infiltrates . Because multiple episodes occurred in several patients, a total of 60 BALs were performed . A diagnosis of fungal pneumonia was eventually made in 12 patients (24 percent) . The organism was identified in BALs from seven of the 12, including five of seven cases of cocciodoidomycosis, one of two cases of aspergillosis, and one of three cases of cryptococcosis . Among the AIDS patients, only one case of coccidioidomycosis was diagnosed, whereas six such diagnoses were made from the 25 BALs performed on the 21 non-AIDS patients . This suggests that coccidioidomycosis is not as frequent an infection in AIDS patients in this endemic area as has been suggested previously . Candida-like organisms were identified in 23 BALs, but in no case were they clinically pathogenic . Their presence correlated with oral candidiasis (p = 0.01) . Twenty-seven of 29 episodes related to Pneumocystis carinii were identified by Papanicolaou-stained cytocentrifuged BAL preparations, all but two of which were in AIDS patients . In addition, BALs detected six episodes of bacterial pneumonia and three of five cases of radiation pneumonitis . Overall, the diagnostic sensitivity of BAL was 52 of 60 or 87 percent . While examination of induced sputum for the presence of Pneumocystis may eliminate the need for bronchoscopy in some AIDS patients, BAL remains an excellent diagnostic procedure in the immunocompromised patient without AIDS.

Semin Oncol, 1990 Jun, 17(3 Suppl 6), 2 - 5
Overview of fungal infections in cancer patients; Brown AE; Because fungal infection is a significant factor that determines the morbidity and the mortality of many patients with cancer, it is essential to understand the various predisposing defects that lead to such infections . These defects may be categorized into two broad areas: immune defects and mechanical defects . Among the immune defects and the fungal organisms that take advantage of them are: neutropenia, absolute neutrophil count less than 1,000/microL, (Candida, Aspergillus, Mucor, Rhizopus, Trichosporon, and Fusarium species); and T-cell defects or impaired cell-mediated immunity (Candida, Cryptococcus neoformans, Histoplasma capsulatum, Coccidioides immitis, and Aspergillus species) . Mechanical defects and the fungal organisms associated with them include: disruption of the natural barrier of the skin, including catheterization of urinary, venous, and arterial systems (Candida and Rhodotorula species); interruption of a natural barrier, ie, the mucous membranes of the gastrointestinal tract and the respiratory tree, by cytotoxic chemotherapy, producing mucositis, (Candida species); contamination of intravenous solutions and blood products (Candida species); and environmental factors during demolition, construction, and renovation (Aspergillus species and other molds) . An understanding of these factors and the fungi that may occur in these various settings leads to earlier diagnosis and treatment, as well as prevention of such fungal infections and reduction of fungal-related morbidity and mortality.

Infect Immun, 1990 Jun, 58(6), 1664 - 70
Production of the hexitol D-mannitol by Cryptococcus neoformans in vitro and in rabbits with experimental meningitis; Wong B et al.; We studied the ability of Cryptococcus neoformans to produce the hexitol D-mannitol in vitro and in rabbits with experimental meningitis . Twelve of twelve human isolates of C . neoformans produced D-mannitol in yeast nitrogen base plus 1% glucose and released D-mannitol into the medium . In a pilot study, pooled cerebrospinal fluid (CSF) from cortisone-treated rabbits given 3 x 10(7) C . neoformans H99 intracisternally contained more D-mannitol (identified by gas chromatography and enzymatically) than CSF from normal controls or cortisone-untreated rabbits with self-limited meningitis . In a second experiment, cortisone-treated rabbits given C . neoformans intracisternally had significantly higher CSF D-mannitol concentrations than controls given cortisone alone at 4, 6, and 8 days after infection . Moreover, log10 CSF D-mannitol correlated well with log10 CSF CFU (r = 0.81) and log10 CSF cryptococcal antigen titers (r = 0.78) . Lastly, the initial volume of distribution and elimination half-life of D-mannitol given intracisternally to normal rabbits suggested that D-mannitol was distributed in total CSF and was removed by CSF bulk flow . Thus, C . neoformans produces D-mannitol in vitro and in vivo, and D-mannitol is a quantitative marker for experimental cryptococcal meningitis . D-Mannitol produced by C . neoformans may also contribute to brain edema and interfere with phagocyte killing by scavenging hydroxyl radicals.

Schweiz Rundsch Med Prax, 1990 May 2, 79(18), 557 - 61
{Opportunistic infections in HIV-infected patients}; Vonwiller HM; HIV-infected patients are prone to frequent opportunistic infections (OI) . Their fundamental differences to infections in the immunocompetent host are explained . The most frequent OI is pneumonia caused by pneumocystis carinii . A brief overview on diagnostic and therapeutic aspects of encephalitis due to toxoplasma gondii, candidiasis, meningitis due to cryptococcus neoformans, tuberculosis, infection by atypical mycobacteria, infection by viruses of the herpes group--in particular cytomegalovirus--and cryptosporidiosis is given.

Indian J Med Sci, 1990 May, 44(5), 115 - 9
Study of systemic fungal infections in autopsy material; Jadhav MV et al.; A retrospective study of 2526 autopsy cases was done in order to find out the pattern of systemic fungal infections . The autopsy records were reviewed for case histories, gross and histological findings . The histological sections from cases showing evidence of fungalo infections were reviewed . The fungal infections were found in 28 cases . Of these 11 (93.29 percent) were aspergillosis, 8 (28.27 percent) were mucormyosis, 6 (21.43 percent) were monilial infections and 3 (10.71 percent) were monilial infections and 3 (10.71 percent) were cryptococcosis . The incidence of systemic fungal infection was 1.11 percent . The most common type of fungal infection was aspergillosis . The maximum number of fungal infection was seen in the respiratory system . The fungal infections presented as opportunistic infections in all but one case . The metabolic disturbance was the most frequent predisposing condition for systemic fungal infections.

Pediatr Neurol, 1990 May-Jun, 6(3), 206 - 8
Spinal arachnoiditis with Cryptococcus neoformans in a nonimmunocompromised child; Woodall WC 3rd et al.; Cryptococcal spinal arachnoiditis occurs in patients with meningitis and usually when they are immunocompromised . It is rare in children . We report a child without evidence of immunologic abnormality who developed paraparesis due to a primary cryptococcal arachnoiditis without meningitis and who improved with adequate therapy.

J Am Vet Med Assoc, 1990 May 1, 196(9), 1470 - 3
Clinical evaluation of a cryptococcal antigen latex agglutination test for diagnosis of cryptococcosis in cats; Medleau L et al.; A commercial cryptococcal antigen latex agglutination test was used to evaluate sera from 20 cats with cryptococcosis and 184 cats without cryptococcosis . Cryptococcal antigen was detected in the sera from 19 of 20 cats with cryptococcosis . Antigen was not detected in sera from any of the cats without cryptococcosis . The test had sensitivity of 95% and specificity of 100%.

Surg Neurol, 1990 May, 33(5), 314 - 9
Ventriculoperitoneal shunt in cryptococcal meningitis with hydrocephalus; Tang LM; Fourteen patients with cryptococcal meningitis were reviewed . All patients had a ventriculoperitoneal shunt for hydrocephalus . Early recognitions and prompt relief of hydrocephalus were useful for eight patients who showed rapid deterioration of consciousness or signs of cerebral herniation . There was no surgical response in four patients who had had weeks of confusion or mental change . It seems, therefore, that the duration of disturbance of consciousness or change of mentality before shunting is critical in determination of the outcome of the treatment . Ventricular shunting was effective in relieving papilledema in five patients . However, the surgery did not prevent the development of papilledema to optic atrophy and subsequent blindness in two patients . Hence, in addition to hydrocephalus with increased intracranial pressure, conditions such as direct invasion of the optic pathways by Cryptococcus neoformans or optochiasmatic arachnoiditis may be responsible for the visual failure . Ventricular shunting was also helpful in restoring paraparesis in one patient . Of the cerebrospinal fluid determinations, low protein concentration was a favorable indicator for surgery . Of the seven patients who received the surgical procedure before the start of antifungal therapy, four showed a significant improvement despite active infection of the central nervous system . None of the seven patients deteriorated because of the surgical operation . Thus, active stage of cryptococcal meningitis does not contraindicate the necessity of shunting, and premedication with antifungal drugs is unnecessary . Also, no shunt-related morbidity and mortality was seen in this study.

Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi, 1990 May-Jun, 31(3), 196 - 201
{Disseminated cryptococcosis mimicking lymphoreticular malignancy: report of one case}; Wu JM et al.; Disseminated cryptococcosis is a rare and often fatal disease in children . The majority of cases usually occur in individuals with defective cell-mediated immunity . We herein reported a 10-year-old boy who presented with fever, body weight loss, lymphadenopathy and marked hepatosplenomegaly . He was admitted under the impression of Hodgkin's disease . However lymph node biopsy revealed diffuse infiltration with polynuclear giant cell and macrophage . Numerous ovoid-shaped microorganisms were found in the cytoplasma of those cells . Cultures of blood, CSF, lymph node, bone marrow and urine all yielded cryptococcus neoformans . The cryptococcal antigen titer of blood was 1:1024 X and that of CSF was 1:64 X . The immune function in terms of T-cell number, mitogen responses, serum immunoglobulin and complement was normal . After the diagnosis of disseminated cryptococcosis was established, the patient was treated with amphotericin B (0.6 mg/kg/day) and 5-fluorocytosine (150 mg/kg/day) for 6 weeks . The patient responded to the treatment very well . Lymphadenopathy and hepatospelomegaly disappeared and no more recurrence was found during the follow-up period of more than 18 months.

Mycoses, 1990 May, 33(5), 215 - 24
Melanin as a virulence factor in pathogenic fungi; Polak A; The pigment melanin is found universally in nature and is attributed to a variety of functions . In some fungi it is thought to play a decisive role in the determination of virulence . This review examines the experimental evidence which has led to an understanding of the mechanisms by which melanin functions in pathogenic fungi, particularly in plant pathogens, in Cryptococcus neoformans and Wangiella dermatitidis.

Acta Med Port, 1990 May-Jun, 3(3), 155 - 8
{Cryptococcosis . A study of 9 strains of Cryptococcus neoformans isolated from immunodeficient patients}; Nobre G et al.; Five strains of Cryptococcus neoformans isolated from the cerebro-spinal fluid and 4 from the blood of AIDS patients, were studied . Although morphologically identical, they differed in the auxanographic pattern . All strains were pathogenic for mice by intracerebral route . Six isolates were sensitive and the other three resistant to 5-fluorocytosine . All strains were sensitive to the other antifungal tested: nystatin, amphotericin B, clotrimazole, miconazole, econazole and ketoconazole.

Infect Immun, 1990 May, 58(5), 1201 - 9
Growth inhibition of Cryptococcus neoformans by cultured human monocytes: role of the capsule, opsonins, the culture surface, and cytokines; Levitz SM et al.; Despite a presumed critical role of macrophages in the host response to cryptococcal infections, previous studies have failed to show growth inhibition of encapsulated Cryptococcus neoformans by human peripheral blood cultured monocyte-derived macrophages (MO-M phi) . Here, we examined whether MO-M phi could be induced to inhibit growth of an encapsulated strain and an isogenic acapsular mutant strain of C . neoformans . MO-M phi were cultured in microwells, and inhibition was measured by comparing CFU at 0 and 24 h after fungal challenge . MO-M phi cultured on plastic surfaces failed to inhibit growth of the encapsulated strain, even in the presence of pooled human serum and/or anticapsular antibody . Moreover, the presence of anticapsular antibody significantly enhanced fungal growth . However, if MO-M phi were cultured on surfaces coated with fibronectin or poly-L-lysine (but not laminin or collagen) and yeast cells were opsonized with pooled human serum, then complete growth inhibition occurred . Preincubation with various concentrations of tumor necrosis factor, granulocyte macrophage colony-stimulating factor, 1,25-dihydroxycholecalciferol, or supernatants from C . neoformans-stimulated lymphocytes failed to activate macrophages for enhanced antifungal activity . The addition of gamma interferon resulted in a significant loss of growth inhibition . For the acapsular strain, complete growth inhibition was observed regardless of the choice of culture surface, opsonins, or cytokines . Fungicidal activity, as measured by a significant decrement in CFU compared with the initial inoculum, was not observed under any conditions tested . These data demonstrate that macrophages are capable of inhibiting cryptococcal growth but that this capacity is markedly influenced by the culture surface, opsonins, cytokines, and the fungal capsule.

Carbohydr Res, 1990 Apr 2, 198(1), 23 - 38
Cell-wall glucans of Cryptococcus neoformans Cap 67; James PG et al.; Purified cell walls derived from Cryptococcus neofromans Cap 67, an acapsular mutant, consisted of 86% Glc and 7.3% GlcNAc . The integrity of the cell walls was disrupted in three successive extractions with 60% 4-methylmorpholine N-oxide (4-MMNO) at 120 degrees . Four 4-MMNO-soluble D-glucopyranans were isolated . Released within 0.5 h was water-insoluble Gi-1, followed by two water-soluble Gs fractions and water-insoluble Gi-2 over 17.5 h . A 4-MMNO-insoluble residue, containing 27% of GlcNAc, was also isolated . Gi-1 and Gi-2 were isolated as precipitates during dialysis of 4-MMNO extracts and were each reduced with NaBH4 to permit their investigation in alkaline solution . Gs-1 and Gs-2 were separated by ion-exchange chromatography of the water-soluble fractions . The structures of the D-glucopyranans were determined by 13C-n.m.r . spectroscopy and by g.l.c.-mass spectrometry of their per-O-methylated derivatives . Gi-1 was a (1----3)-alpha-D-glucopyranan (97%) with some (1----4)-D-glucosidic linkages (3%) and no chain-branching . Gs-1 and Gs-2 were (1----6)-beta-D-glucopyranans branched at O-3 (10-12%) with beta-D-Glcp-(1----3)-beta-D-Glcp side chains . Gs-2 may have approximately 2% more chain branching than Gs-1 . Gi-2 was a D-glucopyranan with 80% of its structure like that of Gi-1, and 20% like that of Gs-1 and -2; the water-insolubility of Gi-2 suggests that these structures were covalently linked . Almost identical D-glucopyranans were obtained from aged cultures that had thickened walls (as observed by electron microscopy).

Nippon Jinzo Gakkai Shi, 1990 Apr, 32(4), 441 - 9
{A case of systemic lupus erythematosus associated with cryptococcal meningitis which was successfully cured by the administration of massive dose of amphotericin B}; Matsuda O et al.; A case of SLE with moderately deteriorated renal function due to lupus nephritis developed cryptococcal meningitis . Long term administration of amphotericin B (cumulative dose 5 g) combined with 5-flucytosine eradicated this fungal infection . Throughout amphotericin B administration urinary excretions of Na and K, as well as plasma HCO3 concentration were monitored, and, Na, K and HCO3 were supplemented orally and intravenously so much as to replace their urinary losses . Neither prominent water-electrolyte disturbance nor severe azotemia, which are the most serious side effects of amphotericin B, did not ensue . This case study indicates that sufficient water.electrolytes supplementation is important to prevent the nephrotoxicity of amphotericin B.

Clin Nephrol, 1990 Apr, 33(4), 174 - 8
Hyponatremia and hypouricemia: differentiation from SIADH; Maesaka JK et al.; Hypouricemia in coexistence with hyponatremia often differentiates the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) from most other causes of hyponatremia . We report clearance studies in 5 cases of hyponatremia and hypouricemia that were not due to SIADH . One had metastatic pancreatic carcinoma with ascites, edema, hypoalbuminemia and hypophosphatemia . Two had adenocarcinoma of the lung with metastasis to the brain in 1, 1 had disseminated cryptococcus and 1 had Hodgkin's disease . None received radiation or known nephrotoxins at least 4 months prior to study . None had serum creatinine greater than 106.1 mumol/l (1.2 mg/dl) . Two had postural hypotension and hyponatremia that responded to saline therapy . Fluid restriction corrected the hyponatremia in all patients, but the hypouricemia, high fractional excretion (FE) of urate, and high urine sodium concentration persisted . In 2 patients studied, ADH was appropriately suppressed after volume repletion but there was a defect in free water clearance due to high renal solute excretion . In contrast to patients with SIADH who correct their defect in renal urate transport with correction of hyponatremia by water restriction, our patients appear to have a persistent renal urate transport defect and abnormality in sodium conservation . Elevated FE urate of greater than 10% after correction of hyponatremia can thus differentiate these patients from SIADH . The diametrically opposing goals of fluid therapy emphasize the importance of differentiating one group from the other.

J Thorac Imaging, 1990 Apr, 5(2), 84 - 6
Pleural cryptococcosis; Conces DJ Jr et al.; Pleural infection by Cryptococcus neoformans is uncommon and when present typically occurs in the immunocompromised host . We report two renal transplant patients who developed pleural cryptococcosis.

Trop Geogr Med, 1990 Apr, 42(2), 133 - 9
Is cryptococcal meningoencephalitis in the tropics a distinct entity? A retrospective study from Thailand; Schmutzhard E et al.; Twenty-four consecutive patients with central nervous system cryptococcosis (C.C.) have been studied retrospectively . In contrary to many reports from America or Europe only two patients suffered from an underlying immunocompromising disease . All patients were treated uniformly by amphotericin B and 5-fluorocytosin . They were monitored closely and dose-adjustment was done according to laboratory data . None of the patients died . Sixteen were available for a six-month post-treatment follow-up: seven had various degrees of neurological long-term sequelae whereas nine had no complaints and neurological examination was without abnormal findings . Our series is compared with others both from tropical and non-tropical countries . In accordance with all but one larger series from the tropics the relatively good prognosis and extremely rare occurrence of C.C . in immunocompromised persons is noted . Since different varieties of Cryptococcus neoformans have been shown to exist in different climate zones, this might be one of the possible explanations for the lack of preceding immune-compromising conditions in persons suffering from C.C . in the tropics and the benign course of disease.

Mycoses, 1990 Apr, 33(4), 157 - 66
Osteomyelitis due to Cryptococcus neoformans in advanced age . Case report and review of literature; Kromminga R et al.; In an 84-year-old man cryptococcosis with a pronounced osteomyelitic course (involvement of a rib, two thoracic vertebrae, the sacrum and a femur) was diagnosed histologically post mortem, thus directing attention to cryptococcosis in advanced age . The presumptive chronic course of the Cryptococcus neoformans (Cr . n.) infection in this patient was ascribed to chronic kidney failure, diabetes mellitus and chronic obstructive lung disease . Special reference is made to the mycological and radiological diagnosis of cryptococcosis of the bones as well as to its pathogenesis, therapy and epidemiology.

Microbiologica, 1990 Apr, 13(2), 151 - 5
Growth of opportunistic yeasts on vitamin-free solid medium; Vidotto V et al.; The growth of some opportunistic yeasts (Candida albicans, Cryptococcus neoformans, Torulopsis glabrata, Rhodotorula rubra, Geotrichum candidum, Trichosporon cutaneum, Saccharomyces cerevisiae) was essayed in a solid minimal synthetic medium without vitamins . From the preliminary results some species (Candida albicans, Cryptococcus neoformans, Rhodotorula rubra, Geotrichum candidum and Saccharomyces cerevisiae) seem to be autotrophic regarding the growth factor considered indispensable for their metabolism and for this reason normally added to the common synthetic media employed.

Antimicrob Agents Chemother, 1990 Apr, 34(4), 651 - 3
Antifungal activity in human cerebrospinal fluid and plasma after intravenous administration of Allium sativum; Davis LE et al.; Commercial Allium sativum (garlic) extract was given intravenously to two patients with cryptococcal meningitis and three patients with other types of meningitis . Plasma titers of anti-Cryptococcus neoformans activity rose twofold over preinfusion titers . Anti-C . neoformans activity was detected in four of five cerebrospinal fluid samples but not in pooled normal cerebrospinal fluid.

Antimicrob Agents Chemother, 1990 Apr, 34(4), 529 - 33
3-Methoxysampangine, a novel antifungal copyrine alkaloid from Cleistopholis patens; Liu SC et al.; Further examination of the active ethanolic extract of the root bark of Cleistopholis patens by using bioassay-directed fractionation resulted in the isolation of a new alkaloid, 3-methoxysampangine (compound I), together with three known alkaloids, eupolauridine (compound II), liriodenine (compound III), and eupolauridine N-oxide (compound IV) . The proposed structure of compound I was based on its physicochemical properties and spectral data . 3-Methoxysampangine exhibited significant antifungal activity against Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans . This is the first report of the isolation of liriodenine (compound III) from the root bark of C . patens.

Infect Immun, 1990 Mar, 58(3), 639 - 45
Human natural killer cells do not inhibit growth of Cryptococcus neoformans in the absence of antibody; Miller MF et al.; The interaction between human natural killer (NK) cells and yeast cells of Cryptococcus neoformans was investigated because experiments in mice indicated that NK cells inhibited the growth of C . neoformans . Strains of C . neoformans serotype A that differed in both resistance to alveolar macrophages and the size and composition of their capsules were evaluated . Human NK cells, which were isolated from normal peripheral blood, were activated by preincubation with interleukin-2 and alpha interferon to generate lymphokine-activated killer (LAK) cells . Yeast cells of C . neoformans were incubated with effector cells (NK or LAK cells); and inhibition of yeast cell growth was measured at 4, 8, and 24 h by comparing quantitative plate counts with controls consisting of yeasts in the absence of effector cells . The cytolytic activity of effector cells against target cells was confirmed by the release of radiolabel from 51Cr-labeled K-562 tumor cells . Neither NK nor LAK cells inhibited the growth of 13 strains of C . neoformans at effector to target cell ratios of as high as 500:1 . Monocytes, which were isolated from the same populations of leukocytes as the NK cells, inhibited the growth of two strains of C . neoformans at effector to target cell ratios of 100:1 (92 and 46% inhibition), 50:1 (87 and 17%), and 1:1 (49 and 0%) . NK cells could inhibit the growth of C . neoformans by an antibody-dependent cellular cytotoxicity mechanism in the presence of rabbit anticryptococcal antiserum at dilutions up to 1:4,000 . Purified capsular polysaccharide of C . neoformans had no effect on the viability or tumoricidal activity of NK or LAK cells . These data suggest that human NK and LAK cells are not impaired by C . neoformans, and in the absence of antibody, which is rarely detectable in patients, they afford much less protection against C . neoformans than monocytes do.

Eur J Clin Microbiol Infect Dis, 1990 Mar, 9(3), 226 - 9
First report of chronic meningitis caused by Trichosporon beigelii; Surmont I et al.; Trichosporon beigelii (Trichosporon cutaneum) was identified as the causative agent of chronic meningitis in a 15-year-old boy with acute lymphocytic leukaemia . After a neutropenic episode following cytostatic treatment and itraconazole therapy as prophylaxis, cerebrospinal fluid (CSF) samples yielded growth of Trichosporon beigelii . Treatment with amphotericin B, flucytosine and high doses of fluconazole was followed by clinical improvement, although CSF pleocytosis remained . The cross-reactivity between Cryptococcus neoformans and Trichosporon beigelii in a cryptococcal antigen latex test was used as a means of diagnosis in CSF and serum samples.

Vet Surg, 1990 Mar-Apr, 19(2), 122 - 30
A large frontonasal bone flap for sinus surgery in the horse; Freeman DE et al.; A large frontonasal bone flap was created to treat diseases of the paranasal sinuses in 14 horses . The bone flap was made as wide as possible within the confines of the nasolacrimal duct so the floor of the frontal sinus and the dorsal and ventral conchae could be opened . These openings exposed the nasal passages, maxillary sinuses, and ventral conchal sinus thereby facilitating removal of diffuse and localized lesions from these sites . Diseases treated were ethmoid hematomas (4 horses), sinus cysts (5 horses), cryptococcal granuloma, osteoma, hemangiosarcoma, pus in the ventral conchal sinus, and periapical infection of a second molar . Four horses were euthanatized during or after surgery, one because of postsurgical pleuritis and pneumonia (horse with osteoma) and three because of their primary problems (cryptococcal granuloma, hemangiosarcoma, pus in the ventral conchal sinus) . Skin suture abscesses that responded to treatment developed in four horses . Ten horses returned to their intended uses, the sinus flaps healed without blemish, and the original problems did not recur . The frontonasal flap technique provided greater access to all paranasal sinuses than methods described previously.

Rev Infect Dis, 1990 Mar-Apr, 12 Suppl 3, S349 - 63
Fluconazole for life-threatening fungal infections in patients who cannot be treated with conventional antifungal agents; Robinson PA et al.; Fluconazole therapy was evaluated prospectively in patients with serious fungal infections who failed to respond to or could not tolerate conventional antifungal therapy . Patients were enrolled if they had a life-threatening fungal infection and conventional therapy had failed to eradicate the infection, had caused serious toxic reactions, or was contraindicated . Patients were treated with 200 mg/day, a dosage that could be increased to 400 mg/d if the initial response was not satisfactory . AIDS was the underlying risk factor in 65% of 232 patients evaluated in the study and in 85% of 151 patients with cryptococcal infection . Fifty-eight patients had active cryptococcal infection; 74% had a satisfactory clinical response, and 75% of 44 patients became culture-negative . Patients with inactive infection had a relapse rate of 4.5/1,000 patient-weeks . Twenty-three of 30 patients with coccidioidal infection and 10 of 14 patients with candidiasis or another mycosis were clinically improved . Five patients (2%) discontinued fluconazole therapy because of adverse effects possibly attributable to therapy . Fluconazole may be effective in the treatment of serious fungal infections in patients who cannot continue conventional antifungal therapy.

Radiographics, 1990 Mar, 10(2), 201 - 15
Acquired immunodeficiency syndrome: correlation of radiologic and pathologic findings in the brain; Balakrishnan J et al.; The appearance on magnetic resonance (MR) and computed tomographic (CT) images of specific central nervous system disorders associated with acquired immunodeficiency syndrome in 12 cases was correlated with autopsy findings . There were three cases of human immunodeficiency virus (HIV) encephalopathy; three, primary lymphoma; three, toxoplasmosis; one, cryptococcosis; one, cytomegalovirus infection; and one, progressive multifocal leukoencephalopathy . MR imaging demonstrated the various cranial lesions more clearly than did CT . On the basis of MR imaging characteristics, HIV encephalopathy could be distinguished from other lesions, particularly progressive multifocal leukoencephalopathy . Basal ganglia were the most common sites of involvement in opportunistic infections and primary lymphoma . Reliable distinguishing features among lesions of the basal ganglia were not found, except for cryptococcal lesions, which had a unique appearance.

Cutis, 1990 Mar, 45(3), 163 - 7
Cutaneous cryptococcosis simulating Kaposi's sarcoma in the acquired immunodeficiency syndrome; Jones C et al.; A forty-one-year-old homosexual man with acquired immunodeficiency syndrome (AIDS) and biopsy proven Kaposi's sarcoma of the oral cavity presented to our clinic with a several month history of violaceous papules and plaques on his trunk and extremities . Although the patient already carried a clinical diagnosis of Kaposi's sarcoma, several biopsies of skin lesions were performed . Tissue specimens demonstrated cutaneous infection with Cryptococcus neoformans . As patients with AIDS have an increased incidence of both Kaposi's sarcoma and opportunistic infections, all progressing lesions should be biopsied in order to avoid missing a treatable life-threatening disease.

Semin Respir Infect, 1990 Mar, 5(1), 80 - 9
Fungal pneumonia in transplant recipients; Zeluff BJ; Fungal pneumonia is an infrequent but devastating complication of solid organ transplantation . The suspicion of fungal pulmonary infections caused by the dimorphic fungi is based on particular knowledge about the recipient's past or present residence in an endemic area . Some fungi, such as Cryptococcus neoformans, Candida sp and Mucor sp are associated with concomitant diabetes mellitus . The level of immunosuppressive therapy is also a major predisposing factor . For some fungi, such as Coccidioides immitis and C neoformans, serologic tests may assist in diagnosis . For aspergillus, Candida sp and Mucor sp culture evidence is not sufficient to determine pulmonary involvement since these fungi may be nonpathogenic saprophytes . Histopathologic proof is required . In patients with abnormal host defenses, treatment of fungal pneumonia is complex . In solid organ transplant recipients it is made more difficult by drug interactions with cyclosporine . Amphotericin B exhibits synergistic nephrotoxicity with cyclosporine and ketoconazole competes with cyclosporine for hepatic metabolism in an unpredictable manner that may result in increased cyclosporine toxicity.

Eur J Clin Microbiol Infect Dis, 1990 Mar, 9(3), 178 - 83
Value of detection of antibodies to Candida albicans germ tube in the diagnosis of systemic candidosis; Quindos G et al.; To test the value of detection of anti-Candida albicans germ tube antibodies by indirect immunofluorescence assay in the diagnosis of systemic candidosis, a retrospective study was done using 126 sera from 27 patients with presumptive systemic candidosis (13 immunocompromised), 165 sera from 45 patients with aspergillosis (29 immunocompromised), 35 sera from eight patients with cryptococcosis (6 immunocompromised), and 101 sera from 101 blood donors . While 21 of 27 patients with systemic candidosis (77.8%) had anti-germ tube antibodies, these antibodies were absent in all patients with cryptococcosis and in all blood donors . They were however detected in 5 of 45 patients with aspergillosis (11.1%) . Ten of 13 (76.9%) immunocompromised patients with candidosis had anti-germ tube antibodies; similar results were obtained in immunocompetent patients with candidosis (78.6%) . The specificity was 96.8%, indicating a high degree of discrimination was possible between systemic candidosis and other invasive mycoses in the patients studied . Anti-germ tube responses did not appear to be significantly reduced in immunocompromised patients.

Rev Infect Dis, 1990 Mar-Apr, 12 Suppl 3, S338 - 48
Overview: treatment of cryptococcal meningitis; Sugar AM et al.; Infections caused by Cryptococcus neoformans cause significant morbidity and high mortality, particularly among immunocompromised patients . Cryptococcal meningitis is an important cause of central nervous system disease and death in patients with AIDS . Although the introduction of amphotericin B has greatly improved the prognosis of patients with cryptococcal meningitis, 30 years of experience have revealed important clinical limitations, including modest efficacy, nephrotoxicity, other clinically significant toxicities, and the inconvenience of intravenous dosing . The discovery of the additive effects of amphotericin B and flucytosine in cryptococcosis resulted in some improvement in efficacy and reduction in amphotericin B-related toxicity . However, approximately 30% of patients with cryptococcal meningitis still fail to respond to therapy . Ketoconazole has not proved useful in treating cryptococcal meningitis . Accumulating evidence suggests that the antifungal triazoles fluconazole, itraconazole, and SCH 39304 represent an advance in the treatment of cryptococcal meningitis, particularly in AIDS patients . Preliminary clinical trials in patients with and without AIDS have indicated that fluconazole and intraconazole are effective and well tolerated as either initial or maintenance therapy . Two large comparative trials of fluconazole and amphotericin B in patients with cryptococcal meningitis (mostly those with AIDS) are under way.

Rev Infect Dis, 1990 Mar-Apr, 12 Suppl 3, S299 - 302
Fluconazole therapy for experimental cryptococcosis and candidiasis in the rabbit; Perfect JR; Fluconazole is a second-generation azole compound with broad-spectrum antifungal activity . It has been examined in several animal models emphasizing important clinical sites of infection with common yeast pathogens . The drug has an excellent pharmacokinetic profile for central nervous system, renal, and ocular infections; at these sites fluconazole has been successful in the treatment of infections with Cryptococcus neoformans or Candida albicans . On the basis of the experience in animals, fluconazole should be critically evaluated in the treatment of human mycoses such as cryptococcosis of the central nervous system and renal/ocular candidiasis . This agent represents the new wave of interest in the increasingly troublesome problem of deep-seated fungal infections.

Rev Infect Dis, 1990 Mar-Apr, 12(2), 181 - 90
Cryptococcal skeletal infections: case report and review; Behrman RE et al.; Cryptococcus neoformans is an uncommon but treatable cause of osteomyelitis that affects both normal and immunocompromised hosts . When not considered as a diagnostic possibility, C . neoformans infection may result in increased morbidity . The spectrum of disease at presentation extends from an asymptomatic patient with an osteolytic lesion on radiograph to a patient with signs and symptoms of systemic disease . Once diagnosis has been established (often by closed aspiration), optimal therapy appears to involve a combination of amphotericin B, flucytosine, and surgical debridement.

Va Med, 1990 Mar, 117(3), 114 - 6
Biliary obstruction and cholestasis in AIDS: case report; Markowitz SM et al.; In summary, we have described a patient with AIDS and a previously unreported cause of biliary tract obstruction . The incidence of cryptococcal visceral lymphadenitis in patients with AIDS and disseminated cryptococcosis is unknown, but, if present, is probably clinically silent in most instances . However, in the differential diagnosis of abdominal pain and cholestasis in such patients, one should consider major biliary duct obstruction due to cryptococcal lymphadenitis.

Antimicrob Agents Chemother, 1990 Mar, 34(3), 448 - 54
Evaluation of Bay R 3783 in rodent models of superficial and systemic candidiasis, meningeal cryptococcosis, and pulmonary aspergillosis; Hector RF et al.; The triazole Bay R 3783 was compared with fluconazole, itraconazole, ketoconazole, and amphotericin B in rodent models of superficial and systemic candidiasis, meningocerebral cryptococcosis, and pulmonary aspergillosis . Overall, Bay R 3783 was comparable or slightly superior to fluconazole and markedly superior to itraconazole and ketoconazole in both survival and short-term organ load experiments in models of candidiasis and cryptococcosis but was less effective than amphotericin B . Of the antifungal agents tested, only Bay R 3783 and itraconazole showed any efficacy in the model of pulmonary aspergillosis.

Rev Med Chil, 1990 Mar, 118(3), 296 - 9
{Cryptococcosis in acquired immunodeficiency syndrome}; Lobos T et al.; The diagnosis of cryptococcal infection was established in 3 patients with AIDS . Infection was meningo-encephalic in all and presented a violent outset . The chemical characteristics of the CSF were normal . Detection of cryptococcal antigen, presence of encapsulated yeast forms revealed by india-ink staining and positive cultures allowed a definitive diagnosis . Response to therapy with amphotericin B alone or in combination with 5-fluorocytosine was poor . A maintenance therapy with fluconazole is recommended.

AJR Am J Roentgenol, 1990 Mar, 154(3), 603 - 6
CT of intracranial cryptococcosis; Popovich MJ et al.; CT scans of 35 patients with intracranial cryptococcal infection were reviewed retrospectively . Studies were normal in 43% of the patients . Positive findings in others included diffuse atrophy in 34%, mass lesions (cryptococcoma) in 11%, hydrocephalus in 9%, and diffuse cerebral edema in 3% . Two unusual types of cryptococcoma were encountered, namely gelatinous pseudocysts and an intraventricular cryptococcal cyst . All findings were nonspecific for CNS cryptococcosis . The results suggest that CNS cryptococcosis should be considered in all patients at risk for the disease who have these abnormal CT findings, no matter what their initial clinical presentation . In addition, MR demonstration of gelatinous pseudocysts in one patient indicates that this technique may be helpful in locating cryptococcal mass lesions not visualized on CT.

J Immunol, 1990 Feb 15, 144(4), 1472 - 7
Depletion of CD4+ (L3T4+) lymphocytes in vivo impairs murine host defense to Cryptococcus neoformans; Mody CH et al.; T cell-mediated immunity has been shown to play an important role in the host defense to Cryptococcus neoformans . Infections due to C . neoformans are increased in patients with AIDS who are deficient in the CD4+ subset of T lymphocytes . Thus, the effect of CD4+ (L3T4+) lymphocyte depletion on murine host defenses to C . neoformans was studied . The mAb GK 1.5 was administered to mice, and CD4+ T lymphocyte depletion was confirmed by the analysis of T cell subsets in blood, spleen, lymph node, and lung . Evidence of a functional defect was confirmed by demonstrating that the splenocytes of treated mice were unable to proliferate in response to class II incompatible spleen cells . Furthermore, delayed type hypersensitivity to C . neoformans was abrogated by CD4+ lymphocyte depletion . Mice depleted of CD4+ lymphocytes were inoculated with a virulent strain of C . neoformans by the i.v . or the intratracheal route . After i.v . inoculation of C . neoformans, the survival of mice depleted of CD4+ lymphocytes was reduced (27.8 +/- 1.8 vs 36.0 +/- 3.1 days, p less than 0.04) . After intratracheal inoculation, C . neoformans disseminated from the lung to extrapulmonary organs . Dissemination occurred earlier in mice depleted of CD4+ lymphocytes compared to mice that received control antibody, and the burden of C . neoformans in extrapulmonary organs was greater in mice depleted of CD4+ lymphocytes than control mice . Surprisingly, there was no increase in the burden of C . neoformans in the lungs of CD4+ lymphocyte-depleted mice . Survival of mice inoculated with C . neoformans and depleted of CD4+ lymphocytes was reduced compared to control mice and was related to the increased rate of accumulation of organisms in the brains of treated mice . The mean survival of GK 1.5-treated mice was 34.1 +/- 0.9 days compared to control mice with a mean survival of 40.6 +/- 9 days (p less than 0.001) . These data suggest that CD4+ lymphocytes play a prominent role in the host defense of infections due to C . neoformans, that CD4+ lymphocytes are required in extrapulmonary organs for optimal clearance of C . neoformans and that CD4+ lymphocytes are critical for survival of mice infected with C . neoformans.

Mycoses, 1990 Feb, 33(2), 73 - 80
Current status of cryptococcosis in Canada; Sekhon AS et al.; The concurrent use of microscopic, cultural, histopathologic and immunologic procedures enabled us to diagnose 91 cases of cryptococcosis, belonging to cutaneous, pulmonary, meningeal and disseminated types, from the time this mycosis was first reported in Canada in 1953 to the present . These cases occurred predominantly in Quebec (43%) followed by Alberta, British Columbia, Ontario, Saskatchewan, Manitoba, New Brunswick and Newfoundland . It is not known whether any Cryptococcus neoformans infections have occurred elsewhere in Canada . The clinical and laboratory findings indicate that infections occurred in debilitated as well as nondebilitated individuals . Nearly 25% of the infections were seen in individuals having the acquired immune deficiency syndrome (AIDS) in provinces of Alberta, British Columbia, Ontario and Quebec . In some of the AIDS cases, the latex agglutination (LA) test demonstrated exceptionally high titres of circulating cryptococcal antigen (1:256 to 1:32,768) . Cr . neoformans infections occurred more commonly in males than in females, and there were 11 fatal cases of cryptococcosis . The incidence of Cr . neoformans in Canada is probably higher than our data suggest because cryptococcosis is not notifiable in Canada and underreporting is likely.

Kansenshogaku Zasshi, 1990 Feb, 64(2), 210 - 7
{Clinical courses and pathological findings in two gay male patients with acquired immunodeficiency syndrome infected in Japan}; Takamizawa S et al.; This is a report on the clinical courses and pathological findings in two gay male patients with acquired immunodeficiency syndrome (AIDS) infected in Japan . Case 1 . A 39 year-old Japanese homosexual male was diagnosed as amebic dysentery complicated with liver abscess on admission . He was placed on Metronidazole with complete relief . Serological tests was positive for AIDS . On second admission, he was found to have pneumocystis carinii pneumonia (PCP) and cytomegalo-viral uveitis . Administration of Pentamidine was partially effective, however the therapy with Azidothimidine was discontinued by bone marrow suppression . On his third admission, he suffered from cryptococcal meningitis and therapy-resistant fungusemia . Finally he died of recurrent pneumonia regardless of appropriate therapies . Autopsy proved extended cryptococcal infection in the brain, meninx, lungs, liver and kidney, and cytomegalo-infection in the lungs, liver and kidney . Furthermore, atypical mycobacteriosis was found in the lymph nodes . There was no active findings compatible with PCP . Case 2 . A 44 year-old Japanese homosexual male was admitted with oral candidiasis and diagnosed as AIDS related complex . He suffered from pneumonia with marked improvement on sulfamethoxazole-Trimethoprim . On his second admission, he developed diarrhea and was found to be infected with Giardia lambia . In addition, cytomegalo-viral infection damaged his eye sight . He died of pneumonia and meningitis shortly there after . Autopsy proved a cytomegalo-viral infection in the lung and colon, old lesions possibly caused by PCP in the lungs, and suppurative meningitis in the meninx . These experiences confirm that AIDS patients can be exposed to several opportunistic infections at the same time in the multiple organs . Furthermore, it is suggested that homosexual patients with AIDS may have unique opportunistic infections such as amebic dysentery or Giardia lamblia unlike other AIDS patients related to hemophilia.

Acta Neurol (Napoli), 1990 Feb, 12(1), 82 - 4
Cryptococcal meningitis and toxoplasma encephalitis in an AIDS patient; Catania S et al.; A black heterosexually HIV-infected woman, initially presented with cryptococcal meningitis (satisfactorily responding to fluconazole treatment), which was soon followed by lethal cerebral toxoplasmosis.

J Urol, 1990 Feb, 143(2), 365 - 6
Granulomatous prostatitis induced by capsule-deficient cryptococcal infection; Milchgrub S et al.; A 59-year-old man with prostatism, in otherwise good health, was treated with transurethral prostatectomy and ketoconazole . At microscopic examination of the prostatic tissue he had acute and chronic prostatitis with granulomatous lesions, in the center of which capsular-deficient cryptococcal organisms were demonstrated . The patient was well without evidence of systemic or local infection at 22 months . The differential diagnosis of granulomatous prostatitis is discussed.

Nippon Hifuka Gakkai Zasshi, 1990 Feb, 100(2), 205 - 9
{A case of cutaneous localized cryptococcosis}; Yamada Y et al.; A 65-year-old Japanese male with cutaneous localized cryptococcosis, which was developed as an erythematous infiltrated plaque on the right side of the face, was reported . The biopsy specimen taken from the lesion showed a granulomatous change with many spores in the dermis . Culture of the biopsy specimen gave Cryptococcus neoformans serotype D . There were no cryptococcal infections in the other organs . The skin lesion was improved by a systemic administration of miconazole . This patient was unusual since the cryptococcal lesion was limited to the skin, nevertheless he was under a severe cellular immunity deficiency . The reason for this may be that the infected C . neoformans strain belonged to serotype D.

Mycoses, 1990 Feb, 33(2), 61 - 9
Detection of circulating galactomannan by Pastorex Aspergillus in experimental invasive aspergillosis; Van Cutsem J et al.; The performance of Pastorex Aspergillus, a new latex agglutination test for the detection of circulating galactomannan in the serum of patients with invasive aspergillosis, was evaluated in a blind trial in standardized guinea-pig models of invasive aspergillosis and other invasive mycoses . In these animal models, the invasive nature of the fungal infection was confirmed by re-isolation of the etiologic agent from the organs of every animal . Ninety-two plasma samples from 42 animals with invasive aspergillosis were submitted to the test . In 41 of these animals, at least one plasma sample was positive with the latex test (sensitivity 97.6%), titers ranging from 1/1 to 1/512 . In general, antigen titers increased as a function of time, reaching the highest values shortly before death . Guinea-pigs infected with Penicillium marneffei also yielded positive agglutination reactions but antigen titers were lower (maximal titer 1/8) . Plasma samples from animals with invasive candidosis (23), disseminated trichophytosis (11) and cryptococcosis (23) were all negative with the latex test . In 80 guinea-pigs without fungal infection, 3 false positive results (titers 1/1) were observed, which means a specificity of 96.2% in this control group.

Acta Odontol Scand, 1990 Feb, 48(1), 77 - 84
Oral yeast infections in immunocompromised and seriously diseased patients; Heimdahl A et al.; The number of immunocompromised patients has increased during recent years . Most fungal infections in these patients are caused by Candida, Aspergillus, Mucor, and Cryptococcus species . Patients with low granulocyte count are at the highest risk of invasive candidal infection . The commonest type of granulocytopenia is observed in connection with malignant diseases of the hematopoietic system . Cytotoxic treatment and radiotherapy of large-body areas tend to produce a significant decrease in circulating granulocytes . Early diagnosis and adequate treatment of fungal infections are mandatory for a successful outcome . In the oral cavity it is important to differentiate between colonization and invasive infection . The optimal approach to diagnosis is a combination of histology and cultivation of specimens obtained from the same site of suspected infection . Prophylaxis of oral fungal infection in immunocompromised patients is generally aimed at preventing colonization.

Am J Dermatopathol, 1990 Feb, 12(1), 63 - 6
Cutaneous mixed infections in AIDS; Pierard GE et al.; We report a new case of mixed infection occurring at the same site of the skin in a human immune deficiency virus-positive patient . Hyperkeratotic and crusted erosions contained fusospirochetal organisms, Cryptococcus neoformans, and another unidentified fungus.

J Clin Microbiol, 1990 Feb, 28(2), 249 - 53
Collaborative evaluation of antigen detection by a commercial latex agglutination test and enzyme immunoassay in the diagnosis of invasive candidiasis; Lemieux C et al.; The Cand-Tec Candida detection system and enzyme immunoassay for serum mannan were retrospectively compared in a controlled collaborative evaluation of antigen detection in 32 patients with candidiasis proven by biopsy or culture from a normally sterile site and with sera drawn within 7 days of inclusion . With a threshold titer of 1/8, which excluded false-positive results in 17 hospitalized patients without candidiasis, sensitivities for all 32 patients with candidiasis were 44% for the Cand-Tec assay and 17% for the enzyme immunoassay . Both assays provided greater sensitivity when sera were drawn within 24 h of inclusion in the study and in the category of patients with invasive candidiasis (57% by Cand-Tec and 33% by enzyme immunoassay) . The Cand-Tec assay gave false-positive results (titer, greater than or equal to 1/8) in 4 of 6 patients with transient candidemia, in 1 of 20 otherwise healthy patients with rheumatoid factor, and in 1 patient with a positive cryptococcal latex agglutination test . Three serum specimens from 3 of 32 patients with candidiasis contained rheumatoid factor and gave titers of greater than or equal to 1/8 by the Cand-Tec assay . Detection of serum mannan by enzyme immunoassay was less sensitive but more specific than the Cand-Tec Candida detection system for the diagnosis of invasive candidiasis.

Infect Immun, 1990 Feb, 58(2), 393 - 8
Characterization of a cell population which amplifies the anticryptococcal delayed-type hypersensitivity response; Fidel PL Jr et al.; Cell-mediated immunity to Cryptococcus neoformans can be detected by delayed-type hypersensitivity (DTH) to a culture filtrate antigen of C . neoformans . Recently, we have identified a population of cells in spleens of mice immunized with cryptococcal antigen that, when transferred to recipient mice at the time of immunization, amplifies the anticryptococcal DTH response . If the cell donor mice are treated with cyclosporin A during induction of the anticryptococcal DTH response, the amplifier cells are not induced, whereas the cells which transfer DTH (TDH cells) are induced . The purpose of this study was to characterize the amplifier cells with respect to their surface and functional properties and, in so doing, determine whether or not the amplifier cells are analogous to long-lived memory cells . We demonstrated that the amplifier cells were nylon-wool-nonadherent, antigen-specific, CD4 (L3T4+ Lyt-2-) T lymphocytes which appear in the spleens of mice 5 days postimmunization with cryptococcal culture filtrate antigen in complete Freund adjuvant . The amplifier T (Tamp) cells are not considered to be memory cells because they are relatively short-lived, being present 14 but not 18 days after the stimulating immunization . Moreover, the amplified anticryptococcal DTH response does not fulfill the criteria of the typical secondary immune (anamnestic) response in that the amplified response does not appear early relative to the appearance of the primary anticryptococcal DTH response, and it does not persist longer than the primary DTH response . We speculate that Tamp cells are not long-lived memory cells but rather act in a T-helper cell capacity to amplify the anticryptococcal DTH response.

Pharmacotherapy, 1990, 10(4), 305 - 7
Pharmacokinetics of fluconazole in serum and cerebrospinal fluid in a patient with AIDS and cryptococcal meningitis; Chin T et al.; The detailed pharmacokinetics of fluconazole in serum and cerebrospinal fluid (CSF) were studied in a patient with acquired immunodeficiency syndrome and cryptococcal meningitis, after an intravenous dose of 400 mg . Fluconazole exhibited a serum elimination half-life of 34.2 hours, distribution volume of 0.56 L/kg, and clearance of 0.19 ml/min/kg . Peak CSF concentration occurred at 4 hours after the dose . Overall penetration of fluconazole based on the ratio of areas under the curve of CSF to serum was 70% . The drug exhibited an excellent pharmacokinetic profile for treatment of central nervous system fungal infections.

J Acquir Immune Defic Syndr, 1990, 3(9), 921 - 4
Impact of AIDS on mortality in San Francisco, 1979-1986; Saunders LD et al.; We used death certificate data for San Francisco residents from 1979 to 1986 to calculate the number of deaths and years of potential life lost before age 65 (YPLL) for leading causes of death . Acquired immune deficiency syndrome (AIDS)-related deaths were defined as including cytomegalovirus infection (ICD-9 078.5); cryptococcal infection (ICD-9 117.5); Pneumocystis carinii pneumonia (ICD-9 136.3); other malignant neoplasms of the skin, site unspecified (ICD-9 173.9); deficiency of cell-mediated immunity (ICD-9 279.1); and unspecified immunity deficiency (ICD-9 279.3) . These deaths increased from 5 (0.1% of all deaths) in 1979 to 534 (6.6%) in 1986 . Of the 1,225 deaths caused by AIDS-related diseases during this period, 1,032 (84%) occurred in men aged 20-49 years . AIDS-related deaths increased between 1979 and 1986 from 0 to 44 (25% of all deaths), 0 to 257 (44%), and 0 to 150 (35%) in men aged 20-29 years, 30-39 years, and 40-49 years, respectively . In 1986, AIDS-related diseases were the third leading cause of deaths and the leading cause of YPLL among male San Francisco residents.

J Clin Lab Anal, 1990, 4(3), 199 - 207
Evaluation of an ELISA for the detection of anti-Histoplasma ribosomal and antihistoplasmin antibodies in histoplasmosis; Raman C et al.; We have developed an indirect sandwich enzyme-lined immunosorbent assay (ELISA) for the detection of antibodies to Histoplasma ribosomes and histoplasmin; we used this test for demonstration of these antibodies in sera from proven cases of histoplasmosis and other infections . Serum dilutions from five negative controls used in each experiment were normalized against 50 normal sera, and a factor of the mean absorbance was used to establish a positive reaction . Antiribosomal antibodies were detected in 97% of the known histoplasmosis patients with ELISA titers ranging from 1:100 to over 1:12,800 . In contrast, antibodies to histoplasmin were detected in only 75% of these sera; titers ranged from 1:100 to 1:12,800 . Cross-reactions with sera from other fungal infections (blastomycosis, coccidioidomycosis, paracoccidioidomycosis, cryptococcosis, candidiasis, and aspergillosis) were seen in 46% of the cases with ribosomes and 37% with histoplasmin . Fifty percent of the sera from tuberculosis patients gave positive reactions with ribosomes and 29% with histoplasmin . These results warrant further studies on the significance of antibodies to ribosomes and histoplasmin in immunity to histoplasmosis.

J Med Assoc Thai, 1990 Jan, 73(1), 12 - 5
Evaluation of latex cryptococcal agglutination test in cryptococcal meningitis; Niemhom S et al.; There is a growing demand for laboratory diagnosis of cryptococcal meningitis, which is partly due to the increasing incidence of AIDS in Thailand . Presently, latex cryptococcal agglutination test (LCAT) is the most sensitive and specific test for laboratory cryptococcal meningitis . However, the test is very expensive and not readily available . LCAT must be developed locally to meet the need in Thailand . Rabbit antibody to C . neoformans was raised and used to sensitize latex particles used in LCAT . The developed LCAT was compared with a reference LCAT . The locally made LCAT was almost identical to the reference LCAT in sensitivity and specificity . It was extensively compared with the culture and India ink examination, in 73 cerebrospinal fluid specimens from cryptococcal meningitis and 155 specimens from other diseases . LCAT was found specific and more sensitive than fungal culture and India ink examination . LCAT is now extensively used in Thailand and recommended by Thai experts for use in all general hospitals . It is a simple, sensitive, specific, rapid and inexpensive tool for both diagnosis, prognosis and follow-up of cryptococcal meningitis.

Retina, 1990, 10(1), 27 - 32
Cryptococcal choroiditis; Carney MD et al.; Two patients with acquired immune deficiency syndrome presented with headaches and fevers . A diagnosis of cryptococcal meningitis was made by lumbar puncture and elevated cryptococcal antigens . Complaints of decreased vision in both patients led to the diagnosis of optic disc edema and cryptococcal choroiditis with yellow-white choroidal infiltrates noted in both eyes of the two patients . Systemic treatment with amphotericin B and 5' flucytosine led to resolution of the choroidal infiltrates . Late visual acuity loss was believed to be secondary to optic atrophy.

J Acquir Immune Defic Syndr, 1990, 3(5), 480 - 4
Cryptococcus neoformans pulmonary infection in HIV-1-infected patients; Clark RA et al.; Cryptococcus neoformans (Cn) is a frequent pathogen in patients infected with the human immunodeficiency virus (HIV-1) . We review the initial presentation and clinical course of 18 HIV-1-infected (HIV+) patients with a Cn pulmonary infection . Simultaneous positive cerebrospinal fluid (CSF) cultures were found in 10 (63%) of 16 examined . The most frequent presenting symptoms were fever (87%) and pulmonary complaints (60%) . Although the most common chest radiographic finding was bilateral diffuse interstitial infiltrates, nodules and cavitary lesions were also seen . Nine (50%) of the 18 patients died within 6 weeks of diagnosis . Of six patients with an isolated Cn pulmonary infection, five have subsequently died . Three of these five patients did not receive maintenance therapy and had confirmed or probable relapse . Patients initially presenting with an isolated Cn pulmonary infection may later show disseminated disease, suggesting that such patients should receive both acute and maintenance therapy.

Rev Neurol (Paris), 1990, 146(2), 153 - 4
{A case of hemiballismus during cryptococcal meningitis}; Namer IJ et al.; We present a case of hemiballismus related to cryptococcal meningitis . A 23 year-old man was hospitalized because of involuntary movements of his left side, confusion, hyperpyrexia, neck stiffness, bilateral papilledema, right hemiparesis and bilateral pyramidal signs . Diagnosis was made by CSF examination demonstrating cryptococci by india ink . CT with contrast showed hyperdense lesions in the head of the right caudate nucleus, in the left internal capsule and in the frontal and occipital lobes . After treatment with amphotericin B, 5-fluorocytosine and haloperidol, he experienced rapid recovery with disappearance of hemiballismus . To our knowledge, this is the first report of hemiballismus caused by cryptococcal meningitis.

Rontgenblatter, 1990 Jan, 43(1), 30 - 3
{Pulmonary cryptococcosis--a rare differential diagnosis of intrapulmonary coin lesions}; Gaa J et al.; In connection with a case of pulmonary cryptococcosis, the clinical manifestations, radiological findings and therapeutic possibilities are discussed . Although pulmonary cryptococcosis is relatively uncommon, the diagnosis should be considered in any immunologically compromised patient with an abnormal chest roentgenogram.

J Med Microbiol, 1990 Jan, 31(1), 21 - 6
Rapid diagnosis of bacterial meningitis by the detection of a fatty acid marker in CSF with gas chromatography-mass spectrometry and selected ion monitoring; French GL et al.; A chemical marker of bacterial meningitis was sought by comparing derivatives of sterile cerebrospinal fluid (CSF) with cultures of organisms in spinal fluid and artificial media . The technique of gas chromatography-mass spectrometry with selected ion monitoring (GC-MS-SIM) was used, optimised for the analysis of fatty acids . Twenty candidate ions were screened, and an ion of mass: charge ratio (m/e) 268 was chosen for detection in clinical specimens . The origin of this marker is unknown, but it is probably the molecular ion of a C16:1 fatty acid . In 135 clinical specimens of CSF examined, the m/e 268 ion was found to be a useful marker for the common organisms that cause bacterial meningitis, giving a sensitivity of 88% and a specificity of 98% . The method was more rapid and more sensitive than conventional microscopy and culture, but CSF containing coagulase-negative staphylococci, Mycobacterium tuberculosis, Cryptococcus neoformans and some other uncommon pathogens gave inconsistent results . Many organisms produced characteristic ion profiles with multiple-ion monitoring, and this method of chemical analysis holds promise for the rapid diagnosis of bacterial infections to genus or species level.

Am J Clin Pathol, 1990 Jan, 93(1), 141 - 4
Disseminated coccidioidomycosis detected by percutaneous liver biopsy in a liver transplant recipient; Dodd LG et al.; The authors report the first case, to their knowledge, of disseminated coccidioidomycosis occurring in a liver transplant recipient . The case is also interesting in that the diagnosis of disseminated coccidioidomycosis was made fortuitously, only after finding the characteristic endosporulating spherules on a percutaneous liver biopsy . In addition, the authors reviewed the literature on post-transplant infection with particular emphasis on fungal pathogens . All studies concurred that Candida species was the most prevalent infecting fungal organism when both localized and disseminated forms of infection are included . Aspergillus was the second most common offender, and disseminated infection was associated with a very grave prognosis for the transplant recipient . Rare infections with Mucor and Cryptococcus neoformans are described in the literature.

Bull Soc Pathol Exot, 1990, 83(4), 425 - 36
{Seroprevalence of HIV infection in a population of neurological patients in the Central African Republic}; Di Costanzo B et al.; In order to evaluate the predictivity of neurological signs and symptoms in african patients, in Bangui's National Hospital Center (Central African Republic), 79 inpatients (aged 15-65 years) presenting with neurological manifestations (vascular attack, proved metabolic coma, or neuro-paludism excluded), and 64 age and sex matched controls in the same ward, without neurological or AIDS-related symptoms, were tested for the presence of HIV1-antibodies . 51/79 (65%) patients with neurological manifestations were HIV1-seropositive, and 10 (16%) of 64 controls (P less than 0.001) . The positive predictive value (PPV) for HIV1 was 100% for patients with cutaneous zona (9 cases), Bell's palsy (4 cases) or cryptococcal meningitis (8 cases) . The PPV for HIV1 was less important for the other neurological disorders: 43% for purulent meningitis (21 cases), 62% for major involvements of the central nervous system, without diagnosed etiology (32 cases; in which 13 were meningo-encephalitis, 16 focal deficits and 3 possible meningeal tuberculosis) . In central Africa, the predictivity of neurological manifestations is high for HIV1 infection that emphasises the need for including neurological signs in clinical case definitions of AIDS in Africa.

Rev Inst Med Trop Sao Paulo, 1990 Jan-Feb, 32(1), 46 - 50
{Fluorescent method (fluorescein diacetate and ethidium bromide) to study the viability of Cryptococcus neoformans in liquor}; Correa B et al.; The utilization of the fluorescent method (fluorescein diacetate DF and ethidium bromide BE), to verify the viability of fungal cells, was studied in 40 samples of liquor, from patients with neurocryptococcosis . For removing leukocytes and red blood cells, which produce interfering fluorescence, good results were obtained with 0.3% saponin solution . After processing of liquor, 0.1 ml aliquots of resulting suspension were mixed to equal volumes of fresh DF-BE solution . The best incubation period for staining was 30 minutes, resulting in good differentiation between viable (green fluorescence) and non viable (red fluorescence) cells.

Ann Pathol, 1990, 10(4), 247 - 57
{Cardiac lesions in acquired immunodeficiency syndrome (AIDS) . Apropos of an autopsy series of 25 cases}; Hofman P et al.; The pathologic study of the cardiac lesions in 25 persons who died of AIDS were studied from autopsies . Most of these patients were intravenous drug abusers (14 cases) . Heart failure was symptomatic and lead to death in 4 cases . This study showed histological abnormalities in 76% of the cases . We observed 12 myocarditis . In 6 cases, pathogenes were found: Toxoplasma gondii (2), Cryptococcus neoformans (2), Candida (1), Aspergillus (1) . A lymphocytic myocarditis was observed in 6 hearts . By immunohistochemical technique, we could distinguish 2 toxoplasmic myocarditis, and in 4 cases, solitary cysts in the myocardium without inflammation . The remaining lesions comprised respectively: 3 lymphocytic pericarditis, 2 marastic endocarditis and 1 dilated myocardiopathy.

J Med Vet Mycol, 1990, 28(3), 197 - 207
Electron cytochemical studies of Cryptococcus neoformans grown on uric acid and related sources of nitrogen; Fiskin AM et al.; Cells of Cryptococcus neoformans grown on xanthine or urate as the sole sources of nitrogen produced numerous, single membrane-bound organelles, deemed to be microbodies . Electron images of these structures showed positive cytochemical staining for catalase and alpha-hydroxy acid oxidase, known marker enzyme activities for microbodies . Microbodies in xanthine and urate-grown cells were cytochemically reactive for the presence of the hydrogen peroxide-producing xanthine and urate oxidases . Molybdenum and phosphorus (elements associated with the cofactor common to nitrogen scavenging enzymes) were detected in the substrate-induced microbodies by X-ray dispersive microanalysis . The single limiting membrane of the substrate-induced microbody was stained by a modified Gomori reaction for the presence of alkaline phosphatase, thereby suggesting the participation of this enzymic activity in the events associated with microbody chemistry.

Bull Soc Pathol Exot, 1990, 83(2), 159 - 69
{Cryptococcosis in Bujumbura, Burundi . Apropos of 80 observed cases in 42 months}; Laroche R et al.; Cryptococcosis is a systemic fungal disease and meningeal or meningoencephalitis involvement is the most serious complication . This is a retrospective analysis of 80 patients admitted from December 1983 to October 1985 (30 cases) and June 1987 to December 1988 (50 cases) in hospital of Bujumbura, Burundi, Central Africa . All patients have an AIDS . Clinically, the meningeal and meningoencephalitis attack prevails in 87% cases . The diagnosis in our study is essentially based on the examination of the CRL . Before the new antifungals, the treatment involved the association of amphotericin B and 5-fluorocytosine, during 6 to 8 weeks . This treatment was badly tolerated and the second falls, when the therapy was stopped, were frequent . Presently, the fluconazole is the best treatment of this affection (ailment?): it enables maintenance therapy for a disease in which the risks of recurrence and reinfection by the environment are not negligible in Africa.

Trans R Soc Trop Med Hyg, 1990, 84 Suppl 1, 14 - 6
Septicaemia in patients with AIDS; Shanson DC; During a 5 year period at St Stephen's hospital, London, septicaemia was detected in 66 patients with the acquired immune deficiency syndrome (AIDS) and in 13 other patients with non-AIDS-associated HIV infections . The most frequent pathogens in patients with AIDS were Mycobacterium avium-intracellulare, Streptococcus pneumoniae, Pseudomonas aeruginosa, Cryptococcus neoformans and staphylococci . A series of HIV-associated septicaemias reported from other centres in different countries has shown great variation in the pattern of aetiological agents observed, which may partly reflect differences in the local socio-economic condition, ethnic backgrounds, other predisposing factors, and blood culture techniques . Salmonella species were a prominent cause of septicaemia in several reports . Most centres have also reported an increasing problem with septicaemias associated with intravenous lines in patients receiving antiviral or other parenteral drug therapy.

Trans R Soc Trop Med Hyg, 1990, 84 Suppl 1, 1 - 6
Opportunistic infections in AIDS in developed and developing countries; Fleming AF; The acquired immune deficiency syndrome (AIDS) is fundamentally the same disease in all parts of the world, but the prevalence of microorganisms in an environment governs the patterns of disease arising from reactivated latent infections, invading pathogens and opportunistic infections . AIDS in Africa has certain characteristic presentations . Enteropathic AIDS is most common: Cryptosporidium and Isospora belli are identified in up to 60% of patients, but it is uncertain whether they are the causes of diarrhoea . Pneumocystis carinii pneumonia is rare . Tuberculosis, both pulmonary and extrapulmonary, is the supreme complicating infection . Herpes zoster is frequently the first clinical presentation, and has a 95% positive predictive value for HIV positivity . Measles may be more frequent in infants born to HIV-infected mothers, and appears to be worse in HIV-infected children . There is accelerated progress of both diseases in patients infected by HIV and Mycobacterium leprae . Salmonellosis is frequent . There is no direct interaction between malaria and HIV, but, by being a potent cause of anaemia, malaria enhances transmission of HIV to children through blood transfusion . HIV-positive subjects are liable to new or reactivated visceral leishmaniasis with dissemination to unusual sites . Cerebral toxoplasmosis is common . There are no apparent interactions between HIV and helminths, although there is one report of hyperinfection with Strongyloides stercoralis . Cryptococcal meningitis has high frequency . Infections with Histoplasma encapsulatum are common in tropical America, but there has been no increase of frequency of H . duboisii in Africa since the advent of AIDS.

Rev Neurol (Paris), 1990, 146(5), 372 - 4
{Fulminating cryptococcal meningoencephalitis . An anatomo-clinical case}; Vermersch P et al.; We report a case of cryptococcal meningoencephalitis in a 52 year-old man . The patient had complained of headache and drowsiness for a few hours before he became comatose with a bilateral sixth cranial nerve palsy . The cerebrospinal fluid contained less than one lymphocyte per cubic millimeter, a low glucose level (0.20 g/l) and numerous Cryptococcus neoformans encapsulated yeasts . A neuropathological study showed that the cortex and midbrain were involved . To our knowledge, such an acute case with death within the first 20 hours has not yet been reported.

Ann Pathol, 1990, 10(2), 99 - 108
{Mycotic infection in immunosuppressed patients . An anatomopathologic study}; Brocheriou C et al.; Mycotic infections are a frequent and often severe complication in the immunosuppressed patient . A review of autopsy findings in 54 cases with gross, histologic and mycologic studies was undertaken among immunocompromised patients after chemotherapy or allogenic bone marrow transplantation: fungal infections were either localized especially in lungs and gastrointestinal tract, or disseminated . Fungi were various: principally Candida and Aspergillus, but also Fusarium, Torulopsis and Trichosporon . In acquired immunodeficiency syndrome (11 autopsy cases), mycotic infections appeared different . Oral and esophageal candidiasis could be found, but cryptococcosis and histoplasmosis were the major generalized mycosis . This study suggests that fungal infections are not the same in patients treated by chemotherapy or bone marrow transplantation, and in acquired immunodeficiency syndrome.

Res Immunol, 1990 Jan, 141(1), 33 - 42
An anti-Cryptococcus neoformans monoclonal antibody directed against galactoxylomannan; van de Moer A et al.; Six monoclonal antibodies (mAb) were produced by immunizing mice with a Cryptococcus neoformans serotype A spheroplast lysate (CNSL) . Two mAb were of the IgG1 isotype; the others were IgM . The results obtained with one IgM mAb (CN6) are reported herein . This mAb recognized the four serotypes of C . neoformans and no cross-reactions were observed with extracts from Cryptococcus melibiosum, Candida albicans, Saccharomyces cerevisiae, Torulopsis glabrata or Trichosporon beigelii . Fractionation of the CNSL by gel filtration revealed that mAb CN6 recognized high molecular weight substances as well as a range of smaller molecules . Indirect ELISA inhibition studies showed that this mAb recognized substances in a cryptococcal culture filtrate . Inhibition studies and agglutination tests using latex beads sensitized with purified CN6 showed that CN6 strongly reacted with the C . neoformans serotype A cell envelope galactoxylomannan-mannoprotein complex (GAlXM-MP) and only weakly with the glucuronoxylomannan (GXM) component . These tests also showed that purified galactoxylomannan (GalXM) from C . neoformans serotype A was more reactive than purified mannoprotein (MP) . An anti-GalXM mAb might be a useful tool for monitoring the clinical course of cryptococcal infections.

Int J Dermatol, 1990 Jan-Feb, 29(1), 41 - 4
Cryptococcal cellulitis in congenital lymphedema; Krywonis N et al.; A 27-year-old woman with intestinal lymphangiectasia and congenital lymphedema developed cryptococcal cellulitis as a result of her underlying depressed cell-mediated immune responsiveness . Prompt therapy with amphotericin B and 5-fluorocytosine resulted in an excellent outcome . The authors believe that the increasing population of patients with depression of cell-mediated immune response will lead to an increase in the frequency with which cryptococcal cellulitis is seen and emphasize that proper evaluation of a patient with presumptive cellulitis includes consideration of fungal, as well as bacterial, etiology.

Haematol Blood Transfus, 1990, 33, 546 - 50
Management of fungal infection in neutropenic patients with fluconazole; Brammer KW; Fluconazole is a new orally absorbed antifungal azole which is effective in the treatment of mucosal and systemic infections caused by Candida, cryptococci and other fungi . In view of its favourable efficacy, safety and pharmacokinetic profile it was considered appropriate to evaluate its use prophylactically in patients undergoing a period of neutropenia . Two hundred and forty-eight patients receiving chemotherapy and/or bone marrow transplantation for the treatment of acute leukaemia, lymphoma or aplastic anaemia, and expected to be rendered temporarily neutropenic, have been entered into an ongoing multicentre comparative clinical study to compare the prophylactic efficacy of 50 mg daily oral fluconazole with that of widely used regimens of oral polyenes . The incidence of suspected fungal infection was less in the fluconazole group (27%) than in the polyene group (45%), the difference being statistically significant (P less than 0.05) . Only one of the suspected infections in the fluconazole group was confirmed mycologically compared with 17 in the polyene group . Fluconazole prophylaxis was well tolerated and it therefore offers a promising new approach to the management of fungal infection in the neutropenic patient . Further studies are warranted to define the optimum dosage for use in this situation.

Ann Med Interne (Paris), 1990, 141(5), 459 - 63
{Hepatic involvement in AIDS . A retrospective clinical study in 71 patients}; Astagneau P et al.; In order to determine the extent of liver abnormalities occurring during acquired immunodeficiency syndrome, the available histological analyses of liver samples (32 biopsies, 52 autopsies) from 71 AIDS patients, for the period 1982-1986, were studied retrospectively . Hepatomegaly was the most common clinical symptom (23 patients, 32.4%), while jaundice was rare, being seen in only 5 cases (7%) . Progressive anicteric cholestasis was the most frequently observed biological anomaly (29/52, 55.7%) . Ten patients had liver infections: 2 Mycobacterium tuberculosis, 8 Mycobacterium avium intracellulare . Cytomegalovirus was present in 3 patients and 1 individual was infected with Cryptococcus neoformans . Granulomatous hepatitis was associated with these infectious agents in 11 patients, but remained unexplained in 11 others . Three patients had cholangitis (2 with CMV inclusions, 1 unexplained) . Among the 32 biopsies, 5 elucidated the origin of unexplained fever . Kaposi's sarcoma of the liver was found in 10/52 autopsy samples (19%) and hepatic lymphoma in 2 cases . Non-specific histological lesions were common: inflammation of the portal spaces (48 cases, 67.6%), steatosis (32 patients, 45%), peliosis hepatis (9 cases, 12.6%) and sinusoidal dilations (39 cases, 54.9%).

J Med Vet Mycol, 1990, 28(1), 77 - 90
Comparative morphological and biological studies on the itraconazole- and ketoconazole-resistant mutants of Cryptococcus neoformans; Iwata K et al.; Studies were carried out on the resistance in vitro of Cryptococcus neoformans to the oral antifungal drugs itraconazole and ketoconazole . None of the six sensitive strains tested developed resistance to itraconazole or ketoconazole by serial transfer on Sabouraud's glucose agar plates containing increasing concentrations of either drug . One mutant resistant to itraconazole, and one mutant resistant to ketoconazole, were isolated from the progenies of yeast cells surviving after treatment with a mutagenic substance, N-methyl-N'-nitro-N-nitroso-guanidine . These mutants were capable of growing in the presence of high concentrations of the drugs to which they were resistant . The itraconazole- and ketoconazole-resistant mutants obtained by mutagenesis were compared morphologically and biologically . The itraconazole-resistant mutant was characterized by the formation of very rough colonies which varied in size and shape, production of a large number of cell clusters, complete loss of capsule formation, and major degenerative changes in the cells, while in the ketoconazole-resistant mutant these changes were less pronounced and no cell clusters were formed . The acquisition of resistance was more stable in the itraconazole-resistant mutant than in the ketoconazole-resistant mutant . Both mutants showed partial cross-resistance and complete loss of virulence for mice.

Pharmacotherapy, 1990, 10(2), 146 - 53
The triazole antifungal agents: a review of itraconazole and fluconazole; Bailey EM et al.; Fluconazole and itraconazole are two investigational triazole antifungal agents that are currently undergoing clinical trials in the United States . Both are active orally, have favorable pharmacokinetics (i.e., good bioavailability, long half-life, low plasma protein binding), and possess activity against several systemic fungal pathogens . In addition, preliminary information suggests that these agents are substantially less toxic than currently available azole compounds . Fluconazole and, to a lesser degree, itraconazole have been shown to be highly effective for the treatment of cryptococcal meningitis . The potential for drug interactions is much lower with these agents compared to drugs such as ketoconazole.

J Med Vet Mycol, 1990, 28(4), 289 - 301
Side group addition by xylosyltransferase and glucuronyltransferase in biosynthesis of capsular polysaccharide in Cryptococcus neoformans; White CW et al.; The capsular polysaccharide of Cryptococcus neoformans consists of an O-acetylated mannan backbone with xylosyl and glucuronyl substituents . We have studied two enzymes in the biosynthetic pathway of this polysaccharide . A particulate enzyme preparation contained xylosyltransferase and glucuronyltransferase activities with pH optima of 7.5 and less than 6.5, and optimum incubation temperatures of 25 degrees and 37 degrees C respectively . O-acetylated mannan served as an acceptor for glucuronyl residues but xylomannan did not . Glucuronomannan served as an acceptor for xylosyl residues but acetylated mannan did not . These observations suggest that glucuronate is added before xylose and after acetate . This hypothesis was supported by studies of lipid-linked sugars in which a microsomal preparation was incubated with various combinations of nucleotide sugars . With GDP-mannose, UDP-glucuronate and UDP-{14C}xylose; GDP-mannose, UDP-{14C}glucuronate and UDP-xylose; or GDP-mannose and UDP-{14C}glucuronate, no evidence for a lipid-linked monosaccharide was obtained . However, lipid-linked xylose was detected only if GDP-mannose and UDP-{14C}xylose were provided, a finding consistent with a pool of lipid-linked xylose which is only transferred following glucuronylation . The order of addition inferred is mannosyl, acetyl, glucuronyl and xylosyl.

Acta Haematol, 1990, 84(2), 101 - 3
Rhinophyma-like cryptococcal infection as an early manifestation of AIDS in a hemophilia B patient; Mares M et al.; A hemophilia B patient, seropositive for HIV antibodies since 1984, came to us in March 1989 with a severe necrotizing lesion of the nose . It was an erythematous lesion and looked like rhinophyma . Microbiological examination of the skin biopsy showed the presence of Cryptococcus neoformans . At the time of the study, the patient was in partial remission after 2 weeks of therapy with fluconazole per os 400 mg/day . He will be treated with the same therapy at maintenance dose (200 mg/day) for a long period.

AJNR Am J Neuroradiol, 1990 Jan-Feb, 11(1), 139 - 42
CT of intracranial cryptococcosis; Popovich MJ et al.; CT scans of 35 patients with intracranial cryptococcal infection were reviewed retrospectively . Studies were normal in 43% of the patients . Positive findings in others included diffuse atrophy in 34%, mass lesions (cryptococcoma) in 11%, hydrocephalus in 9%, and diffuse cerebral edema in 3% . Two unusual types of cryptococcoma were encountered, namely gelatinous pseudocysts and an intraventricular cryptococcal cyst . All findings were nonspecific for CNS cryptococcosis . The results suggest that CNS cryptococcosis should be considered in all patients at risk for the disease who have these abnormal CT findings, no matter what their initial clinical presentation . In addition, MR demonstration of gelatinous pseudocysts in one patient indicates that this technique may be helpful in locating cryptococcal mass lesions not visualized on CT.

Prog AIDS Pathol, 1990, 2, 51 - 60
Bone marrow findings in HIV infection: a pathological study; Marche C et al.; The histopathologic changes of bone marrow during infection with the human immunodeficiency virus type 1 (HIV-1) are described . Bone marrow biopsies from 73 patients at different stages of HIV-1 infection were studied . Indications for biopsy included peripheral blood abnormalities, suspicion of lymphoma, or search for specific pathogens . Common histopathological features, suggestive of HIV-1 infection but nonpathognomonic were hypercellularity (67%), myelodysplasia (86.1%), plasmacytosis (98.6%), lymphocytic infiltration (31.1%) and histiocytic infiltration with or without granulomata (13.7%) . Increases in reticulin fibers (54.7%), and stainable iron deposits, vascular congestion and serous atrophy of fat were frequent features . Opportunistic infections and neoplastic complications were detected in 7 cases: pathogens were demonstrated in 4 cases (Mycobacterium avium intracellulare (MAI), Cryptococcus neoformans, Toxoplasma gondii and Leishmania) and lymphoma in 3 cases (1 Burkitt lymphoma and 2 Hodgkin's disease) . Bone marrow hypoplasia is usually a terminal event in AIDS and may be iatrogenic.

Mycoses, 1990, 33 Suppl 1, 55 - 64
{Cryptococcosis in AIDS: therapeutic concepts}; Ruf B; Cryptococcosis is the most common life-threatening mycosis with AIDS . The combination therapy based on amphotericin B and flucytosine is furthermore the therapy of first choice, even after introduction of fluconazole . With a therapy maintained over a period of 6 weeks the combination is nearly always successful; a shorter treatment period leads to minor treatment success . Since no elimination of the pathogen is possible in cryptococcosis with AIDS a permanent relapse prevention is necessary . In this prevention strategy fluconazole is highly effective and at present the drug of first choice; it is as effective as amphotericin B . An additional advantage is the possibility of oral application.

Mycoses, 1990, 33 Suppl 1, 14 - 8
{Collection of cases in relation to clinical trials of fluconazole in Germany}; Krisch H et al.; Fluconazole is a new antifungal agent from the class of triazoles for systemic treatment of fungal infections caused by Candida or Cryptococcus . From September 1988 to June 1990, fluconazole has been made available free of charge in a clinical trial for the treatment of patients who failed to respond to conventional therapy or in whom conventional therapy was limited due to side effects etc . (compassionate usage program) . Overall, 1,188 patients were entered including 79 with cryptococcal meningitis, 665 with life-threatening and 444 with non-life-threatening candidosis . The following results were found in an interim evaluation of 254 cases: The therapeutic success (cure and improvement) was 43% in patients with cryptococcal meningitis, 54% in life-threatening candidosis and 67% in non-life-threatening candidosis.

Rev Soc Bras Med Trop, 1990 Jan-Mar, 23(1), 19 - 25
{Cryptococcus meningitis: clinical course, development and histopathologic aspects depending on the predisposing factors}; Fiorillo AM et al.; Seventeen consecutive cases of cryptococcal meningitis diagnosed at Hospital das Clinicas of Ribeirao Preto Medical School (Sao Paulo State Brazil) between 1969 and 1985 were reviewed . For analysis the patients were separated in 3 groups: I . three patients without immunodeficiency; II . six patients with associated disease: cancer (3), diabetes (2) and alcoholism (1); III . Eight renal transplant recipients that developed cryptococcosis after 18 to 67 months of immunosupression with steroids and azathioprine . The median interval between onset of symptoms and diagnosis of infection was greater in Group II (53 days) than in Groups I (25 days) or III (28 days) . Neck stiffness, cranial nerve involvement and papilledema were more frequent in Group I than in Group II or III, but fever and focal neurological signs were observed only in patients of two last groups . Cerebrospinal fluid examination showed a mild lymphocytic pleocytosis in most patients, but transplant cases had polymorphonuclear cells more frequently . Late mortality was higher in patients with underlying disease and the prognosis was better for transplant patients that received effective antifungal therapy . Besides cryptococci, autopsy findings in 8 cases revealed granuloma formation in tissues, except in patients of Group II (2 cases) . The differences between the groups suggest that clinical characteristics, evolution and postmortem findings of the cryptococcal meningitis are changed according to type of immunodeficiency presented by the patient.

Drugs Exp Clin Res, 1990, 16(7), 327 - 32
Treatment of cryptococcal meningitis with five anti-fungal drugs: the role of amphotericin B; Shindo K; Experiments are described of the treatment of two patients with cryptococcal meningitis using antifungal drugs and amphotericin B . The first patient was a 56-year-old man with a slight azotaemia caused by hypertensive nephrosclerosis . Lumbar puncture revealed a positive India ink stain and a positive culture for Cryptococcus neoformans; serum titre for cryptococcal antigen was elevated . Amphotericin B was not administered because of the patient's slight azotaemia . After admission, the patient received oral and intravenous fluconazole (400 mg per day), for a total dose of 40 g of fluconazole over 103 days from October 1 while simultaneously receiving treatment with oral itraconazole (200 mg per day) from October 1 to December 5 . In addition, he was given intravenous miconazole (600-1000 mg per day, total 74.4 g) and intrathecal miconazole (5-20 mg per day, total 375 mg) from December 1 to March 4 1990 . Concomitantly, oral flucytosine (6 g per day) was given from December 5 to March 1 1990 . Lumbar puncture performed at the completion of these treatments indicated the India ink stain still was positive and the serum titre for cryptococcal antigen high . Finally, amphotericin B alone was administered to the patient intravenously and intrathecally from March 4 to May 1, with an initial dose of 5 mg i.v . gradually increasing by 5 mg increments up to 50 mg per day . The patient's clinical symptoms immediately improved; the India ink stain became negative for the first time after admission and the serum titre for cryptococcal antigen also gradually decreased . On May 1, the patient was completely cured of cryptococcal meningitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Microbiol Immunol, 1990, 34(10), 825 - 40
Reassessment of antigenic determinant of Saccharomyces cerevisiae serotype Ia; Nishikawa A et al.; We examined the immunochemical structure of the antigenic determinant of S . cerevisiae serotype Ia . The specific factor serum for S . cerevisiae serotype Ia was obtained either from factor 18 serum by adsorption with heat-killed cells of Candida glabrata, or from anti-S . cerevisiae Ia (M 6001) serum by adsorption with heat-killed cells of S . cerevisiae Ib (IFO 0751) . We designated this adsorbed serum as factor 18a . Acetolysis of S . cerevisiae cell wall D-mannan gave five oligosaccharides . Signals of 1H-nuclear magnetic resonance spectra of mannooligosaccharides derived from S . cerevisiae mannan were assigned for their linkages by the aid of those of alpha-1,3'-linked mannooligosaccharides derived from glucuronoxylomannan of capsule of Cryptococcus neoformans serotype A-D . Agglutination-inhibition experiments revealed that the mannopentaose from S . cerevisiae mannan was the most effective inhibitor . Moreover, inhibitory activities of alpha-1,3'-linked mannotriose, mannotetraose, and mannopentaose which were derived from glucuronoxylomannan of C . neoformans were shown to be higher than those of mannotetraose with one terminal alpha-(1-3) linkage from homologous S . cerevisiae mannan . These results indicate that mannopentaose with terminal two alpha-(1-3) linkages is responsible for the specificity of S . cerevisiae Ia.

Ann Trop Paediatr, 1990, 10(3), 323 - 6
Cryptococcal meningitis in a child with systemic lupus erythematosus; al-Rasheed SA et al.; This is a case report of fatal cryptococcal meningitis in a child with systemic lupus erythematosus being treated with prednisolone and azathioprine . It is believed to be the first case of cryptococcal meningitis recorded in a child in Saudi Arabia.

Oncology (Huntingt), 1989 Dec, 3(12), 15 - 22; discussion 23
Optimal use of the Ommaya reservoir in clinical oncology; Sundaresan N et al.; A major obstacle to the effective systemic therapy of intracranial malignancies and infections, the bloodbrain barrier was overcome by the development of the Ommaya reservoir in 1963 . Initially used in treating cryptococcal meningitis, this closed system for continued access to the ventricular spaces has a variety of applications . They include treatment of cancer pain, chronic or recurrent CNS infection, prophylaxis of CNS involvement in acute lymphoblastic leukemia, and treatment of leptomeningeal malignancy . The authors outline the rationale, latest indications, surgical technique, and potential complications arising from the use of the Ommaya reservoir and other such subcutaneous reservoirs.

South Med J, 1989 Dec, 82(12), 1555 - 6
Cryptococcal pyarthrosis complicating gouty arthritis; Sinnott JT 4th et al.; Cryptococcal arthritis remains a rare entity . Crystalline arthropathy has been described in association with bacterial infection, but no similar association has been described for crystalline joint disease and fungal infection . We have described a renal transplant patient with concurrent gout and cryptococcal arthritis that responded favorably to treatment . Joints with crystalline arthropathy should be cultured for both bacteria and fungi.

J Bacteriol, 1989 Dec, 171(12), 6850 - 2
Localization of mannoprotein in Cryptococcus neoformans; Vartivarian SE et al.; Cell wall mannoprotein of nonpathogenic yeasts is surface exposed, since the cells are agglutinated by concanavalin A and antimannoprotein antibodies . However, nonencapsulated cells of Cryptococcus neoformans were agglutinated neither by concanavalin A nor by antimannoprotein antibodies . Immunogold electron microscopy located most mannoprotein in the inner cell wall . Chemical analysis of purified cell walls showed the lack of mannose, xylose, and galactose residues . These data indicate that cryptococcal mannoprotein recovered from the cultural supernatant is a nonstructural element of the cell wall.

Arch Neurol, 1989 Dec, 46(12), 1312 - 6
Cryptococcal meningitis . False-negative antigen test results and cultures in nonimmunosuppressed patients; Berlin L et al.; All cases of cryptococcal meningitis at Yale-New Haven (Conn) Hospital seen during a 4 1/2-year period were reviewed to calculate the rate of false-negative antigen test results and cultures preceding diagnosis . Of 13 patients, 9 were immunosuppressed and were diagnosed following the initial lumbar puncture, with both antigen test results and cultures positive in all cases . Among 4 nonimmunosuppressed patients, the rate of false-negative antigen test results was 77%, and of cultures, 89% . The diagnosis was consequently delayed in 3, 2 of whom died despite treatment . Cryptococcal meningitis may be underdiagnosed and undertreated to a significant degree in nonimmunosuppressed patients.

J Leukoc Biol, 1989 Dec, 46(6), 521 - 8
Phagocytosis and killing of Cryptococcus neoformans by rat alveolar macrophages in the absence of serum; Bolanos B et al.; The in vitro interaction between yeast cells of Cryptococcus neoformans and Lewis rat alveolar macrophages (AM phi) was studied in the absence of serum . AM phi were harvested by lung lavage, and monolayers of adherent cells were established in wells of microtiter plates . Radiolabeled yeast cells were added to fresh AM phi monolayers, the plates were incubated at 37 degrees C under 5% CO2, nonadherent yeasts were removed, and phagocytosis (i.e., attachment or ingestion) was determined by measuring adherent radioactivity . AM phi were able to bind or ingest, and kill, encapsulated strains of C . neoformans in the absence of serum . Serum-free phagocytosis was suboptimal by comparison with phagocytosis in the presence of serum . The mechanism of serum-free phagocytosis involves a receptor on the AM phi with affinity for mannose-rich determinants present on the yeast cell walls and unrelated to the capsular polysaccharide . Opsonin-independent phagocytosis was only detected with nonencapsulated, small, and medium encapsulated strains of C . neoformans . Large encapsulated strains were not taken up without serum . Serum-free phagocytosis could be of critical importance in the alveolar spaces, where only marginal concentrations of serum opsonins are initially present.

Infect Immun, 1989 Dec, 57(12), 3882 - 7
Characterization of Cryptococcus neoformans capsular glucuronoxylomannan polysaccharide with monoclonal antibodies; Todaro-Luck F et al.; Mice were immunized with Cryptococcus neoformans serotype A capsular glucuronoxylomannan (GXM) conjugated to bovine serum albumin-adipic dihydrazide . Two splenocyte fusions yielded two monoclonal antibodies (MAbs) that were highly reactive in dot enzyme immunoassay, immunofluorescence, and sandwich enzyme immunoassay . The first MAb, BD-1 {immunoglobulin G1 (kappa) {IgG1(kappa)}}, was GXM-A and GXM-D specific, whereas the second MAb, BA-4 (IgM), reacted with GXM-A and GXM-B . A third MAb, CD-6 {IgG1(kappa)}, originated from mice immunized with O-deacetylated GXM-C-bovine serum albumin and reacted with GXMs of all four serotypes . Two of the MAbs (CD-6 and BD-1) were further characterized with chemically modified GXMs . Removal of glucuronosyl residues completely inhibited the binding of both MAbs, implicating (1----2)-beta-glucuronic acid as a key component of the epitope . Removal of (1----2)-beta-xylosyl residues decreased reactivity to an intermediate extent . O deacetylation led to a measurable decrease but had the least inhibitory effect of the three GXM derivatives tested . The combining site for these two MAbs appears to be a complex antigenic determinant involving more than one glycosidic residue.

Infect Immun, 1989 Dec, 57(12), 3751 - 6
Strain variation in antiphagocytic activity of capsular polysaccharides from Cryptococcus neoformans serotype A; Small JM et al.; Strains of Cryptococcus neoformans vary in resistance to phagocytosis in vitro . The binding of isolated capsular polysaccharide (CPS) to a capsule-free mutant of C . neoformans confers resistance to phagocytosis . The importance of capsule composition to differences among strains in susceptibility to phagocytosis was evaluated . CPSs from five strains of C . neoformans serotype A, designated 6, 15, 98, 110, and 145, which had previously been isolated and characterized as to molecular size, composition, and binding properties, were evaluated for relative antiphagocytic potencies . In the presence of 5% normal isologous serum, murine thioglycolate-elicited peritoneal macrophages phagocytized (i.e., attached to or engulfed) 80% of 51Cr-labeled cells of C . neoformans 602, a capsule-free mutant . Added CPS inhibited the uptake of these yeast cells . CPS from strain 110 was most potent, followed in decreasing order of inhibitory activity by CPSs from strains 6, 145, 98, and 15 . The presence of 100 micrograms of strain 110 CPS per ml reduced uptake of cells of strain 602 from 80 to 50% . CPS had no effect on the uptake of 51Cr-labeled Saccharomyces cerevisiae . Cells of strain 602 that were preincubated with CPS and then washed were more resistant to phagocytosis than nonpretreated control cells, indicating the importance of bound, not free, CPS . Added CPS did not affect the uptake of wild-type, encapsulated cells of C . neoformans . Addition of endotoxin had no effect on phagocytosis . CPSs from strains of C . neoformans serotype A varied widely in their abilities to inhibit the uptake of capsule-free cells . The antiphagocytic activity of CPS did not correlate with the ability to bind to capsule-free mutant but was somewhat related to the capsule size of the strain from which the CPS was isolated.

Arq Neuropsiquiatr, 1989 Dec, 47(4), 385 - 91
{Acquired immunodeficiency syndrome: analysis of neurologic complications in 44 cases}; Puccioni M et al.; We studied the clinical records of 280 patients admitted to our Hospital between 1985 and 1988, with a positive Elisa test for HIV-related antibodies: 15.71% (44) of these patients exhibited clinical abnormalities related to disease of the CNS . In 6 (13.6%) patients the neurological complication was the first manifestation of HIV-infection . Patients were mainly male homosexuals, in the 30-39 age range . Frequent chief complaints included hemiparesis, headache and behavior disturbances . Cerebral toxoplasmosis was diagnosed in 18 instances . It should be considered the first diagnostic possibility in patients presenting with mass lesions . Meningeal infections were present in 19 cases (cryptococcal in 13, tuberculous in 4, HIV-related in 2) . CSF findings in these patients were non specific, except for demonstration of Cryptococcus neoformans on direct examination of CSF or culture studies . CT scans frequently displayed unique or multiple hypodense lesions . The lesions exhibited ring-enhancement in 7 instances, and were non-enhancing in 8 others . Cortical and subcortical atrophy with hydrocephalus ex-vacuum were occasionally found, and the CT scans were normal in 8 instances . Time from appearance of the various neurological complications to death or clinical resolution was almost always shorter than 6 months . Death was the most frequent outcome, usually occurring within 6 months . Survival in the most of these patients never reached the end of the first year.

Nihon Kyobu Shikkan Gakkai Zasshi, 1989 Dec, 27(12), 1534 - 9
{Primary pulmonary cryptococcosis treated with transbronchial injection of amphotericin B}; Kaneko T et al.; A 76-year-old man was admitted because of multiple nodular opacities in both lungs on chest X-ray . Cryptococcus was identified in the specimens obtained from bronchial brushing and bronchial washing . Primary pulmonary cryptococcosis was diagnosed as he had no underlying diseases and no foci in any other organs except the lung . Transbronchial injection (TBI) of amphotericin B was administered to the largest focus, in addition to the intravenous administration of miconazole . The chest tomogram 25 days after the first TBI showed marked decrease in the size of the largest focus, but no improvements were observed in other foci . TBI can be performed easily and safely, and perhaps more effectively than administration of amphotericin B with aerosol . This procedure may be of value in the treatment of pulmonary cryptococcosis.

Rinsho Shinkeigaku, 1989 Dec, 29(12), 1546 - 9
{Neuropathology of AIDS: Montefiore experience}; Hirano A; From September 1982 to December 1988 113 cases of AIDS have been autopsied and the brains examined at Montefiore Medical Center . Findings in four areas were presented; 1 . Opportunistic infections In approximately one third of cases there were opportunistic infections which were often the cause of death . Cryptococcus, cytomegalovirus and toxoplasma were the three most common infections followed by papovavirus (progressive multifocal leukoencephalopathy) and herpes zoster . Tuberculosis, aspergillosis, histoplasmosis and infection with mycobacterium avium-intracellulare infection were found in only one case each . 2 . Malignant lymphoma Both primary and metastatic lymphomas were seen in almost 10% of the cases . 3 . HIV encephalitis This conclusion is regarded as the pathological substrate of "AIDS dementia complex" described by the neurologists . In general, it was characterized by cerebral atrophy and diffuse pallor of the white matter with gliosis . The basal ganglia and other areas of the CNS were also often involved . Histologically, there was perivascular infiltration of lymphocytes, macrophages and multinucleated giant cells . Microglial nodules were commonly seen . Electron microscopic and other techniques demonstrates the HIV virus within macrophages and multinucleated cells . 4 . Cerebrovascular lesions These lesions are known in AIDS but their high frequency is not generally appreciated unless a careful search for microinfarcts is made . Microinfarcts were found in approximately 1/3 of our cases.

Nippon Kyobu Geka Gakkai Zasshi, 1989 Dec, 37(12), 2502 - 6
{Surgical treatment of mycotic lung diseases}; Shirakura T et al.; Eighteen cases of mycotic lung disease, which included 17 pulmonary aspergillosis and one cryptococcosis, were treated surgically . Lobectomy was performed in 4, segmentectomy in 1, partial resection of lung in 4, cavernostomy in 2, open window thoracotomy in 4 and exploratory thoracotomy in 1 . The authors would like to emphasize following points; 1) Of eighteen, cases, there were five patients over 70 years old and results of surgery in those were uneventful . 2) Two cases developed the postoperative empyema which was caused by the remnant lesion invaded with aspergillus fumigotus . From this experience it was considered that in the invasive aspergillosis the limited resection of the lesion was not recommended because of its local recurrence . 3) Omentopexy was effective for the treatment of mycotic empyema.

J Antibiot (Tokyo), 1989 Dec, 42(12), 1756 - 62
Cispentacin, a new antifungal antibiotic . II . In vitro and in vivo antifungal activities; Oki T et al.; Cispentacin {-)-(1R,2S)-2-aminocyclopentane-1-carboxylic acid) is a new antifungal antibiotic possessing potent anti-Candida activity . The 50% inhibitory concentration (IC50) and IC100 values of cispentacin against clinical isolates of Candida albicans were in the ranges 6.3 approximately 12.5 and 6.3 approximately 50 micrograms/ml, respectively, by turbidimetric measurement in yeast nitrogen base glucose medium . No significant activity was seen against any yeasts and molds when tested by the agar dilution method using three different agar media: KNOPP's agar, yeast extract-glucose-peptone agar and Sabouraud dextrose agar . This antibiotic demonstrated good therapeutic efficacy against a systemic Candida infection in mice by both parenteral and po administrations . The 50% protection dose (PD50) values after single iv and po administrations were 10 and 30 mg/kg, respectively . It was also effective in a systemic infection with Cryptococcus neoformans and in both lung and vaginal infections with C . albicans in mice . Cispentacin did not induce acute lethal toxicity at 1,000 mg/kg by iv injection and 1,500 mg/kg by ip and po administrations in mice.

Antimicrob Agents Chemother, 1989 Dec, 33(12), 2118 - 25
In vitro and in vivo activities of piritetrate (M-732), a new antidermatophytic thiocarbamate; Iwata K et al.; Piritetrate (M-732), a new topical antifungal agent belonging chemically to the thiocarbamates, was demonstrated to possess a potent selective antidermatophytic activity . In terms of its MICs in susceptibility testing, mainly done by using Sabouraud dextrose agar plates, piritetrate exhibited several- to 10-fold-stronger antidermatophytic activity than tolnaftate, a reference thiocarbamate . Furthermore, piritetrate was found to show a broader antifungal spectrum than tolnaftate; relatively many species and strains of dematiaceous fungi, dimorphic fungi, and some other filamentous fungi as well as a few strains of Cryptococcus neoformans were fairly susceptible to piritetrate, while almost all the tested species and strains were resistant to tolnaftate . All the tested species of the genus Candida were, however, resistant to both compounds . Variables which can influence antimicrobial activity caused few changes in the MICs of either compound against Trichophyton mentagrophytes; however, an increase in the inoculum size resulted in a significant increase in the MICs . The antidermatophytic activities of piritetrate and tolnaftate were fungistatic but not fungicidal . Piritetrate also exhibited a more potent in vitro anti-T . mentagrophytes activity than clotrimazole or tolciclate . Piritetrate and tolnaftate had no antibacterial activity . The in vivo activity of topically administered piritetrate against experimental dermal infection of guinea pigs with T . mentagrophytes was more effective than that of tolnaftate both mycologically and clinically . Piritetrate manifested no acute toxicity in laboratory animals when administered even in large quantities by the oral, intraperitoneal, and topical routes.

Clin Exp Immunol, 1989 Dec, 78(3), 412 - 7
Role of IgG and complement component C5 in the initial course of experimental cryptococcosis; Dromer F et al.; Although cellular immunity has a crucial role during cryptococcosis, several in vitro studies have pointed out the importance of IgG anti-Cryptococcus neoformans antibodies and complement components during phagocytosis of the yeast by polymorphonuclear leucocytes and monocytes . We investigated the role of complement and specific antibodies in host defences against experimental cryptococcosis, using a monoclonal IgG1 antibody (E1) specific for cryptococcal capsular polysaccharide, and mice congenitally sufficient or deficient in the fifth component of complement (C5) . During in vitro experiments, E1 and the normal mouse serum from C5-sufficient and -deficient mice were unable to inhibit the growth of C.neoformans . However, E1 was an efficient opsonin for the ingestion of C . neoformans by mouse peritoneal macrophages, acting in synergy with normal mouse serum . In vivo, E1 was protective in heavily infected C5-deficient mice (DBA/2) dying from an early acute pneumonia, but not in C5-sufficient mice (BALB/c) and in DBA/2 mice infected with a smaller inoculum dying from a late progressive meningo-encephalitis . Although protection against pneumonia is attributed to a local recruitment of phagocytes in C5-sufficient mice, this was not observed in C5-deficient mice protected with E1 . In this case, IgG anti-C . neoformans antibodies seem to be an alternative for an efficient opsonization of the yeasts . Altogether, these data suggest that two main mechanisms may protect infected mice from an early fatal pneumonia: the efficient opsonization of the yeast by complement and the recruitment of phagocytes in infected tissues.

Am J Dermatopathol, 1989 Dec, 11(6), 560 - 2
Formation of palisading granulomas in a patient with chronic cutaneous cryptococcosis; Leidel GD et al.; We describe a unique case of a 57-year-old man who developed a chronic cryptococcal infection with cutaneous lesions that showed palisading granulomas . To our knowledge, this is the first report of this entity in the skin . We also discuss the differential diagnosis of palisading granulomas.

J Gen Microbiol, 1989 Dec, 135 ( Pt 12), 3353 - 62
Restriction fragment polymorphism in mitochondrial DNA of Cryptococcus neoformans; Varma A et al.; The restriction patterns of mitochondrial DNA from 20 isolates of the two varieties of Cryptococcus neoformans were compared . The patterns exhibited extensive heterogeneity among the isolates regardless of their serotype or varietal status . Hybridizations with cloned fragments of the conserved cytochrome oxidase gene from Saccharomyces cerevisiae exhibited at least seven patterns among the 20 isolates . There were, however, similarities in the restriction patterns among isolates within the same serotype that were not shared by isolates of other serotypes . Intra-varietal similarities were observed in the restriction patterns among the isolates of C . neoformans var . neoformans which were not present in the restriction patterns among the isolates of C . neoformans var . gattii . Hybridization of some cloned mitochondrial DNA fragments to total DNA digests of various isolates revealed polymorphic as well as variety-specific patterns of homology . These findings agree with the antigenic heterogeneity among the isolates and support the current taxonomic classification of C . neoformans into two varieties.

J Pak Med Assoc, 1989 Dec, 39(12), 312 - 6
Neurological disorders in AIDS: a study of 18 cases; Sonawalla AB et al.; Neurological disorders were studied in 18 patients diagnosed to have AIDS and their findings are analysed . Amongst the problems seen were toxoplasmosis (9), cryptococcal meningitis (5), tuberculous meningitis (1), AIDS dementia complex (3), peripheral neuropathy (2), vertebrobasilar stroke, and a possible AIDS myelopathy in one case each . Their findings are discussed, and literature on the neurological disorders in AIDS reviewed.

Mol Cell Probes, 1989 Dec, 3(4), 345 - 61
Immunoelectronmicroscopic characterization of monoclonal antibodies (MAbs) against Cryptococcus neoformans; Todaro-Luck F et al.; Three monoclonal antibodies (MAbs) (BA4, BD1, CD6) reacted with Cryptococcus neoformans capsular glucuronoxylomannan (GXM) polysaccharide showing distinctive patterns against four serotypes as revealed by enzyme immunoassay (EIA), dot EIA, and immunofluorescence . Immunoelectron microscopy (IEM) was used to characterize binding sites for the MAbs on the C . neoformans capsule . All three MAbs bound to the capsule of serotype A strains 9104 and 9759 . Differences in the intensity of binding to the two serotype A strains could not be explained by capsule diameter . The MAb BA-4 IgM bound well to 9759 (large capsule) and poorly to 9104 (small capsule), whereas MAb BD-1 (IgG-1) bound well to strain 9104 and poorly to strain 9759 . Spurr's embedment inactivated the BA-4-binding epitopes in the C . neoformans 9759 capsule, but did not inactivate the ones that bound to BD-1 . The epitopes recognized by BA-4 were different than the BD-1-binding determinants . The MAb CD-6 bound to a cytoplasmic precursor of capsular GXM . CD-6 (IgG) stained the capsule, cell wall, and cytoplasm of both C . neoformans tester strains . Competitive binding experiments were conducted . Single immunogold labelling showed that BD-1 inhibited the binding of BA-4, but not vice versa . The interaction between CD-6 and BA-4 resulted in a reciprocal inhibition . Double-labelling experiments showed reciprocal inhibition between BA-4 and each of the IgG MAbs . These MAbs are directed against capsular polysaccharide or its intracellular precursor . None of the MAbs stained C . neoformans cap 67, an acapsular mutant that does not contain GXM.

Ugeskr Laeger, 1989 Nov 6, 151(45), 2974 - 5
{Occurrence of the yeast, Cryptococcus (Cr) neoformans, in pigeon droppings}; Stenderup J et al.; Pigeon droppings were collected in Copenhagen and Odense . In samples from pigeon lofts, cryptococci were found in 33% from Copenhagen and in 16% from Odense . All of the species of cryptococci found were Cr . neoformans . These findings are compared with the previous Danish investigations . The frequent occurrence of cryptococci in AIDS patients is mentioned.

Biochim Biophys Acta, 1989 Nov 3, 985(3), 307 - 12
Concentration dependent dual effect of the monolauryl ester of sucrose on the antifungal activity and absorption spectra of amphotericin B (Fungizone); Brajtburg J et al.; A mild detergent, the monolauryl ester of sucrose (LS), at concentrations which ranged from 0.008 to 0.03%, enhanced amphotericin B (AmB) toxicity against Saccharomyces cerevisiae and Cryptococcus neoformans cells . At higher concentrations, 0.06 to 2.5%, LS inhibited AmB effects on these two fungi . We analyzed changes in the absorption spectrum of AmB induced by LS at these two concentration ranges by comparing ratios (R values) of AmB absorbance at 409 nm, the wavelength characteristic of non-aggregated (monomeric) AmB, to absorbance at 328 nm, the wavelength characteristic of aggregated AmB . Low concentrations of LS caused a decrease in R, whereas the higher LS concentrations increased R . Therefore, LS had concentration-dependent dual effects on the antifungal activity of AmB which correlated with shifts in the physical states of AmB . The concentration range of LS required to inhibit the antifungal effects of AmB was about 1000-fold greater than the previously reported concentrations required to inhibit AmB toxicity to mammalian cells (Gruda, I., Gauthier, E., Elberg, S., Brajtburg, J . and Medoff, G . (1988) Biochem . Biophys . Res . Commun . 154, 954-958) . This suggests that LS may be a useful agent to decrease AmB toxicity to host cells without affecting the antifungal effects . Moreover, increase in AmB toxicity induced by low concentrations of LS suggests the possibility that synergistic interaction between fatty acid esters and polyene antibiotics may have therapeutic value.

Angiology, 1989 Nov, 40(11), 970 - 6
Treatment of AIDS-associated heart disease; Kinney EL et al.; Although the diagnosis of AIDS-associated heart disease is becoming routine, its treatment has not been reported except in anecdote . Also, it has been unclear whether the odds of successful treatment are altered because of the presence of cardiac involvement per se . This communication reports the authors' treatment of 18 patients with AIDS-associated heart disease . Their results are combined with the treatment results of all patients reported in the literature to date with AIDS-associated heart disease . Treatment success, defined as eradication of the organism and no relapse, was achieved in their patients with M . tuberculosis (M . tb), cardiac cryptococcosis, and Salmonella typhimurium . M . tb required emergency pericardiectomy (well tolerated in all patients), then administration of rifampin, isoniazid, and ethambutol . Cryptococcosis was treated acutely with amphotericin B and flucytosine, then with maintenance amphotericin B . The response, which included resolution of congestive heart failure, occurred within a week . Salmonella endocarditis was cured with administration of ampicillin and netilmicin for one month . When the patients' data were combined with those of patients from the literature, the authors found that the odds of successful treatment for tuberculous pericarditis were somewhat lower than if the tuberculosis was extracardiac (50% vs 67%) . With cryptococcal heart disease, the odds of successful treatment were actually significantly better than when only extracardiac disease was present . The authors conclude that infectious forms of AIDS-associated heart disease are often treatable . Although some cardiac infections are less likely to respond to treatment if there is cardiac involvement, mostly the response to treatment is similar to the response with only extracardiac involvement.

Nihon Kyobu Shikkan Gakkai Zasshi, 1989 Nov, 27(11), 1330 - 4
{A case of multiple cavities on chest film with high titer of serum cryptococcal antigen}; Maeda J et al.; A 26-year-old man admitted to Nishinomiya Municipal Hospital for further evaluation for abnormal shadows on the chest film in a mass examination . He had no subjective complaints; for example, cough, sputum or dyspnea . His past history and physical examinations yielded no significant findings . The chest film revealed the multiple cavities accompanied with a little infiltration throughout several lobes bilaterally . The inflammatory reactions; such as, CRP and ESR, were all intact, but the titer of the serum cryptococcal antigen was high . He was not immunocompromised . Although bronchoscopy and transbronchial lung biopsy were performed twice during admission, they revealed no pathogenic findings both bacteriologically and histologically . The elevation of the serum cryptococcal antigen titer suggested that this disease is the primary pulmonary cryptococcosis . The titer decreased with spontaneous disappearance of the abnormal shadows on the chest film . This test has a sensitivity of 90% for cryptococcal infection, but in rheumatoid arthritis, a small percentage of false positive results have been reported . Therefore, if the rheumatoid factor is eliminated, the test is more specific for cryptococcal infection . On the other hand, some authors have reported the false positive results in Trichosporon beigelii infection by this method . But this disease is negligible for its frequency in clinical features in our country . We emphasized that this non-invasive test is more useful for the diagnosis of the primary pulmonary cryptococcosis.

Rev Infect Dis, 1989 Nov-Dec, 11(6), 970 - 4
Profound muscle weakness as the presenting feature of disseminated cryptococcal infection; Hurd DD et al.; A patient with chronic lymphocytic leukemia who was treated with immunosuppressive therapy for a prolonged period presented with profound muscle weakness secondary to disseminated cryptococcosis . The infection developed despite 3 months of continuous ketoconazole therapy and was not responsive to amphotericin B or flucytosine . At autopsy, Cryptococcus neoformans was present in all sampled skeletal muscles, myocardium, and muscularis propria of the gastrointestinal tract but was not identified in either the central nervous system or the lungs . A review of the English-language literature failed to identify a similar case with such profound myotropism due to Cryptococcus . This case demonstrates that cryptococcosis should be considered in the differential diagnosis of an immunocompromised host presenting with muscle weakness.

J Infect Dis, 1989 Nov, 160(5), 882 - 6
Prophylaxis of Pneumocystis carinii pneumonia: an update; Kovacs JA et al.; Note from Dr . Merle A . Sande--We have recently come to appreciate the fact that successful chemotherapy of opportunistic infections in patients with AIDS is akin to treatment of certain malignancies: In both instances, induction, followed by maintenance, therapy is required . Although control of initial infections is usually successful with current regimens, relapse is common if lifelong prophylactic or suppressive therapy is not used . This is true in human immunodeficiency virus (HIV)-infected individuals with Pneumocystis carinii pneumonia, cryptococcosis, histoplasmosis, toxoplasmosis, and cytomegaloviral infection . Because Drs . Joseph A . Kovacs and Henry Masur of the National Institutes of Health have been instrumental in developing strategies for the management of P . carinii pneumonia, they were asked to discuss their current approach to chemoprophylaxis of this infection in this AIDS Commentary.

Taiwan Yi Xue Hui Za Zhi, 1989 Nov-Dec, 88(11-12), 1160 - 2
Large mass-like pulmonary cryptococcosis: report of 2 cases; Hsu WH et al.; Pulmonary cryptococcosis, a less common fungal infection, frequently reveals nodular lesions (single or multiple) and patchy infiltrations (alveolar or interstitial) on chest X rays . A large mass-like pattern is less common . Here we report 2 cases of pulmonary cryptococcosis with negative bronchoscopic findings . One patient received a right lower lobectomy under the impression of malignancy; the other received a transthoracic needle aspiration, and numerous cryptococci were found by India ink preparation . Thus, pulmonary cryptococcosis should be included in the differential diagnosis of a mass lesion . A brief review of the literature is also included about diagnostic approach and management of pulmonary cryptococcosis.

Mycopathologia, 1989 Nov, 108(2), 81 - 8
Comparative study of four antifungal drugs in an experimental model of murine cryptococcosis; Bava AJ et al.; A comparative study among amphotericin B, 5-fluorocytosine, itraconazole and fluconazole in the treatment of experimental cryptococcosis in mice, was carried out . Seventy male Balb C mice were inoculated intraperitoneally with 10(7) cells of Cryptococcus neoformans var . neoformans . They were divided in 7 groups of 10 animals each one: 1) treated with fluconazole by gavage at a daily dose of 16 mg/kg; 2) treated with itraconazole by gavage at a daily dose of 16 mg/kg; 3) treated with 5-fluorocytosine by gavage at a daily dose of 300 mg/kg; 4) treated with amphotericin B intraperitoneally at a dose of 6 mg/kg every other day; 5) control animals receiving polietilenglicol 200 by gavage; 6) control animals receiving distilled water by gavage and 7) control animals receiving sterile distilled water by intraperitoneal route . All the treatments started 5 days after the challenge inoculation and they were given for 2 weeks . The following parameters were taken into account: survival time, macroscopic aspect of the organ after the complete autopsy, microscopic investigation of yeasts in brain, lungs, spleen and liver, histopathology studies of these organs, the colony forming units per gram and massive seeding of brain and lungs . The survival index of the different groups was the most efficient method to measure the antifungal compounds activity . Amphotericin B increased significantly the animals survival and modified the histopathologic response in the studied organs . The colony forming units and the massive seeding in brain and lung showed that this antifungal agent is unable of producing the biological cure of this experimental model.(ABSTRACT TRUNCATED AT 250 WORDS)

Gastroenterol Clin Biol, 1989 Nov, 13(11), 942 - 3
{Cryptococcus neoformans meningitis and cirrhosis . Value of fluconazole}; Levesque H et al.; We report the case of a 80-old-year woman with cryptococcal meningitis and cirrhosis . The diagnosis of this rare infectious complication is probably underestimated in patients with cirrhosis . Of diagnostic value is the detection of cryptococcal antigen in cerebral fluid . Fluconazole could improve an otherwise poor prognostic.

J Antimicrob Chemother, 1989 Nov, 24(5), 747 - 63
In-vitro effects of cilofungin (LY121019), amphotericin B and amphotericin B-deoxycholate on human polymorphonuclear leucocytes; Van der Auwera P et al.; The in-vitro influence of cilofungin (LY121019) and amphotericin B on human polymorphonuclear leucocytes (PMNs) was studied by a multifunctional approach . Cilofungin at high concentration (greater than or equal to 20 mg/l) increased adherence to plastic and ingestion of Staphylococcus aureus by PMNs in suspension and Candida albicans by adherent PMNs, and slightly decreased MTT reduction and superoxide generation . Amphotericin B and amphotericin B-deoxycholate decreased adherence to plastic (IC50: 5.1 and 8.2 mg/l respectively) and superoxide generation induced by PMA and opsonized zymosan (IC50 1.1 mg/l for amphotericin B-deoxycholate) . Variable results were observed for intra-cellular killing and ingestion . The functional assessment was made with four clinical isolates of yeasts (Can . albicans, Can . tropicalis, Can . Torulopsis) (glabrata, Cryptococcus neoformans) . The inoculum was preincubated with the antifungals (PRE) or they were added during (PER) or after ingestion (POST) using PMNs in suspension (PRE and PER), or adhering to plastic (PRE, PER and POST) . With the scheme PRE, killing was usually increased with amphotericin B-deoxycholate and cilofungin . With Crypt . neoformans, ingestion was also increased by the antifungals and sodium-deoxycholate, probably by altering the capsule . The results of the scheme POST showed that amphotericin B-deoxycholate, but not cilofungin, increased intracellular killing of Can . albicans, Can . tropicalis and Can . glabrata.

Rev Infect Dis, 1989 Nov-Dec, 11 Suppl 7, S1591 - 9
Problems in management of opportunistic fungal diseases; Armstrong D; Opportunistic fungal infections are now common and will become more common as a consequence of the use of various regimens of immunosuppressive therapy for a variety of diseases and because of AIDS . These infections can be broadly divided into those that take advantage of a neutrophil defect (e.g., candidiasis, aspergillosis, and mucormycosis) and those that take advantage of a T cell mononuclear phagocyte defect (e.g., cryptococcosis, histoplasmosis, and coccidioidomycosis) . Problems in diagnosis have been apparent since these infections were first recognized . The usual clinical specimens are often not revealing, and attempts to develop special serologic and biochemical tests have been made for years, but progress has been slow . Problems in treatment stem first from a lack of an early diagnosis and second from a lack of drugs that are effective and relatively nontoxic . It is difficult to evaluate new drugs if we cannot make accurate diagnoses; this difficulty is compounded by the low rate of autopsies in the academic hospitals where such studies are conducted.

J Am Vet Med Assoc, 1989 Oct 1, 195(7), 954 - 6
Ketoconazole therapy in a dog with systemic cryptococcosis; Mason GD et al.; A 2-year-old dog had bilateral chorioretinitis and a cough . Systemic cryptococcosis was diagnosed by evaluating a trans-tracheal aspirate and a cryptococcal latex-particle agglutination antigen titer . Clinical remission was achieved with ketoconazole administration, an imidazole antifungal agent . Serial antigen titers were used to monitor treatment, which was continued for 12 months . Ketoconazole therapy was well tolerated by the dog.

Infect Immun, 1989 Oct, 57(10), 2931 - 7
Characterization of the macrophage subset affected and its response to a T suppressor factor (TsFmp) found in cryptococcosis; Blackstock R et al.; Previous reports from our laboratory described the detection of a suppressor factor which inhibited the phagocytic activity of a macrophage subset in murine cryptococcosis and in classical models of immune tolerance . The suppressor factor was originally named PIL (phagocytosis-inhibiting lymphokine) but has recently been renamed TsFmp (T suppressor factor for macrophage phagocytosis) because it was found to resemble the antigen-specific I-J-restricted suppressor factors described by others . The current investigation revealed that TsFmp acted rapidly upon the macrophage (15 min or less) to exert its effect of inhibiting the phagocytic process . The time for the macrophage to recover from the effects of TsFmp was likewise very rapid . The ability of TsFmp to inhibit phagocytosis was limited to engulfment of particles by Fc and mannan receptors and did not extent to phagocytosis via complement receptors or by nonspecific mechanisms . The macrophage subset that responded to TsFmp was determined to be in the I-A+ and I-J-IM+ subset.

Mycopathologia, 1989 Oct, 108(1), 65 - 7
Clinical and environmental isolates of Cryptococcus neoformans in Bangkok (Thailand); Imwidthaya P et al.; Cryptococcus neoformans was isolated from 13 patients (7 females and 6 males) suffering from systemic cryptococcosis . Eight patients were suffering from central nervous system cryptococcosis and 5 were suffering from disseminated cryptococcosis . Systemic lupus erythematosus was found to be the common underlying disease in 3 patients . The results of treatment depended on the underlying diseases (7 improved, 6 died) . Also, 13 isolates of C . neoformans were obtained from feces of 30 pet birds . All 26 isolates of C . neoformans were cultured in glycine cycloheximide medium and were found to be of serotypes A and D.

Kansenshogaku Zasshi, 1989 Oct, 63(10), 1206 - 11
{A case of sepsis and meningitis due to capsule-deficient Cryptococcus neoformans with SIADH}; Mukae H et al.; Capsule-deficient Cryptococcus neoformans (CN-CD) infection is very rare . The authors recently experienced the case of CN-CD infection with the complication of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) in a 83 year old woman . She was admitted to our hospital with the complaints of fever and general fatigue on June 10, 1987 . At the time of admission, there were no abnormal findings except a mildly lowered consciousness level on physical examination, there were no abnormal neurological finding nor meningeal signs . Laboratory data revealed a mild leukocytosis and hyponatremia . Chest X-P showed a few small nodular shadows scattered in both lungs . Antibiotics therapy was of no help and hyponatremia became worse . Then with the suspicion of SIADH, Demeclocycline was administered and limitation of water intake was decreased and hyponatremia improvement was used . Yeast-like fungi was detected in the venous blood culture and in the cerebrospinal fluid (cell count: 252/3) CN-CD by India-ink preparation and bacteriological nature were determined . We made a diagnosis of sepsis and meningitis by CN-CD accompanied with SIADH . In spite of Miconazole administration intravenously and intrathecally, she died 2 months after admission . The minimal inhibitory concentration (micrograms/ml) of antibiotics against the isolated CN-CD was as follows: Amphotericin B: 0.78, 5-PC: 1.56, Miconazole less than or equal to 0.05, Nystatin: 25, Ketoconazole: 0.78.

Mycoses, 1989 Oct, 32(10), 516 - 23
Aspergillus findings in AIDS patients suffering from cryptococcosis; Staib F et al.; Because of the known pathogenicity of Cryptococcus neoformans and of aspergilli depending on defined but different immunodeficiencies of the host, the evaluation of their simultaneous cultural detection in specimens of the respiratory tract of AIDS patients is of epidemiological, diagnostic, pathogenetic and therapeutic interest . In 10 out of 15 AIDS patients the following species of the genus Aspergillus could be isolated either once or repeatedly during the course of Cr . neoformans infections in specimens from the respiratory tract: A . fumigatus, A . flavus, A . nidulans, A . niger and A . glaucus . From the 10 different case reports the conclusion can be drawn that the cultural findings of aspergilli in specimens from the respiratory tract during the course of cryptococcosis were of no pathogenic significance . Rather, they should be interpreted as inhaled and not yet germinated conidia still capable of growth lacking primary pathogenicity for the AIDS patient . The significance of serodiagnosis for the evaluation of the simultaneous occurrence of Cr . neoformans and Aspergillus spp . is demonstrated and discussed.

Childs Nerv Syst, 1989 Oct, 5(5), 281 - 7
Acquired immune deficiency syndrome in childhood . Neurological aspects; Iannetti P et al.; Central nervous system (CNS) involvement is very frequently observed in pediatric AIDS . Clinical manifestations include encephalopathy, cognitive deficits, acquired microcephaly, neurological signs, myelopathy, and peripheral neuropathy . Neurological complications can be related to opportunistic viral infections such as encephalitis, atypical aseptic meningitis, progressive multifocal leukoencephalopathy, and myelitis . Nonviral syndromes include: toxoplasmosis, cryptococcal meningitis, candidiasis, Mycobacterium tuberculosis meningitis, and Mycobacterium avium subacute encephalitis . Bacterial infections, tumors, cerebrovascular complications, and peripheral neuropathies are not frequently observed in pediatric AIDS . The most severe complications of HIV infection is encephalopathy resulting from HIV infection of brain tissue . Direct HIV invasion of the CNS has been demonstrated . Clinical features of HIV encephalopathy are classified into three categories: (1) normal neurological findings; (2) static encephalopathy; and (3) progressive encephalopathy . AIDS dementia complex can be differentiated from the predominance of behavioral and cognitive disabilities.

J Bacteriol, 1989 Oct, 171(10), 5596 - 600
Cloning of 18S and 25S rDNAs from the pathogenic fungus Cryptococcus neoformans; Restrepo BI et al.; Cryptococcus neoformans is an important pathogenic fungus that has been classified as a basidiomycete . Little is known of the molecular genetics of this fungal pathogen . To begin such studies, we devised a procedure for extraction of DNA from cryptococci; this method involved the use of the cell wall-active enzyme NovoZym 234 . Using cloned rDNA of Saccharomyces cerevisiae as a probe, we identified homologous restriction fragments in a Southern blot of digested C . neoformans DNA . An 8.6-kilobase HindIII fragment that hybridized with the yeast rDNA probe was ligated with the vector pBR322 and cloned into Escherichia coli . When the fragment was used as a probe, it hybridized to the 18S and 25S rRNAs of C . neoformans in Northern (RNA) blots of native and denatured RNA . It bound at high stringency only weakly to the rRNAs of the ascomycete S . cerevisiae . The locations of the genes for 5/5.8S, 18S, and 25S subunits in the cloned fragment were identified with labeled rRNA of these different types.

Zhonghua Shen Jing Jing Shen Ke Za Zhi, 1989 Oct, 22(5), 294 - 6, 319
{CSF examination in cryptococcus meningitis}; Chen Y; CSF studies of 14 cases of cryptococcus meningitis revealed: 1 . Direct discerning of yeast cells in the blood cell counting chamber, by Indian ink stain, and by cytological examination based on Sayk's technic, all were highly positive in repeated examinations . 2 . Morphology of cryptococcus and inflammatory cellular reactions in CSF were investigated, and were quite characteristic . 3 . Suppression and destruction of yeast cells were attainable only when doses of amphotericin B were sufficient.

Mycopathologia, 1989 Oct, 108(1), 5 - 10
Immunosuppression in experimental cryptococcosis in rats . Induction of thymic suppressor cells; Sotomayor CE et al.; The presence of the microorganism, cortical hyperplasia and germinal centers was detected in the thymus of rats infected with 10(7) viable Cryptococcus neoformans cells and immunized at 7 days afterwards with 2.5 mg (0.1 ml) of human serum albumin (HSA) incorporated to complete Freund's adjuvant (CFA) (Group 2) . There was no modification of the glandular structure in the thymus of the animals only immunized with HSA-CFA (Group 1) . The weight of the thymus of group 2, animals infected and immunized, was increased compared with the weight of the thymus of group 1 animals, this became evident by the increase of the thymic index (TI) (p less than 0.005) . This rate was obtained calculating the thymus weight/total body weight ratio x 1000 . Thymic cells (10(7) cells in 1 ml) obtained from both groups of animals were transferred to normal syngeneic rats of the same sex . The recipient rats were immunized with HSA-CFA 24 h later and 14 days after the transference, the response of delayed-type hypersensitivity (DTH) was studied in them . It could be observed that the thymic cells coming from group 2 animals were capable of suppressing significatively the afferent pathway of the DTH response to HSA when compared with the response of the animals that received cells coming from group 1 rats (p less than 0.0001).

Antimicrob Agents Chemother, 1989 Oct, 33(10), 1735 - 40
Treatment of experimental cryptococcal meningitis and disseminated candidiasis with SCH39304; Perfect JR et al.; We studied the pharmacokinetics and in vivo antifungal action of SCH39304, a new antifungal azole compound, in rabbits . It crossed the blood-cerebrospinal fluid barrier in the presence or absence of meningeal inflammation, reaching approximately 60% of the simultaneous concentrations in serum . In the treatment of experimental cryptococcal meningitis, SCH39304 was as effective as fluconazole in reducing yeast counts in the subarachnoid space . SCH39304 and fluconazole both were highly effective against candida endophthalmitis, sterilizing the vitreous humor and the choroid and retina . SCH39304 suppressed candida endocarditis and reduced yeast counts in the kidney at all doses tested . SCH39304 was effective in the treatment of experimental cryptococcal meningitis and disseminated candidiasis . Further investigations in humans are warranted.

Mycoses, 1989 Oct, 32(10), 527 - 30
Antifungal activity of diethyldithiocarbamate; Allerberger F et al.; Sodium diethyldithiocarbamate (DTC) was evaluated for its ability to combat four different species of fungi in vitro . Using a microtiter-broth-dilution method we were able to demonstrate an antifungal activity against Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus and Mucor mucedo in doses achievable by intravenous administration in man.

Arch Intern Med, 1989 Oct, 149(10), 2301 - 8
Itraconazole therapy for cryptococcal meningitis and cryptococcosis; Denning DW et al.; We studied the efficacy of itraconazole, a new oral triazole, in 33 patients (32 were immunocompromised) with cryptococcosis . Diagnoses included cryptococcal meningitis (24 patients), cryptococcemia (19 patients), cryptococcuria (4 patients), osteomyelitis (1 patient), pulmonary cryptococcosis (1 patient), and soft-tissue cryptococcosis (2 patients) . Twenty-six patients had the acquired immunodeficiency syndrome, and 4 were transplant recipients . Therapy (200 mg two times per day) was monitored by clinical response, culture, and cryptococcal antigen testing . Cryptococcemia was abolished in 10 (100%) of 10 assessable patients; clinical abnormalities also cleared . Thirteen (65%) of 20 assessable patients with cryptococcal meningitis had complete responses (clinical resolution and negative cultures), 5 (25%) had partial responses, and therapy failed in 2 (10%) . Ten (71%) of 14 patients with the acquired immunodeficiency syndrome who had meningitis and were treated with itraconazole as their sole therapy had complete responses, 3 (21%) had partial responses, and therapy failed in 1 (7%) . Partial responses or failures were all associated with the failure of previous therapy, severe disease, low serum itraconazole concentrations, or a resistant organism . Noncompliance was associated with relapse (4 patients) . Meningitis recrudesced in 3 (20%) of 15 patients who responded to therapy . All 4 patients with pulmonary cryptococcosis, soft-tissue cryptococcosis, or osteomyelitis responded to therapy (100%) . Cryptococcuria was abolished in 3 (60%) of 5 assessable patients . The median survival of the 20 patients with the acquired immunodeficiency syndrome who had meningitis exceeded 10.5 months at this writing . Overall results compare favorably with amphotericin B therapy with or without flucytosine . Forty of 44 isolates of Cryptococcus neoformans were susceptible in vitro to itraconazole (minimum inhibitory concentration less than or equal to 3.13 mg/L), 3 were borderline (minimum inhibitory concentration, 6.25 mg/L), and 1 was resistant (minimum inhibitory concentration, 12.5 mg/L) . As itraconazole does not penetrate cerebrospinal fluid, the meningitis results are noteworthy and suggest that meningeal and parenchymal penetration is critical . Itraconazole is promising for the treatment of cryptococcosis in patients with and without the acquired immunodeficiency syndrome.

Infect Immun, 1989 Oct, 57(10), 3240 - 2
Antigenic variation within serotypes of Cryptococcus neoformans detected by monoclonal antibodies specific for the capsular polysaccharide; Spiropulu C et al.; The serotype-specific polysaccharide was isolated from four to seven strains of each of the four major serotypes of Cryptococcus neoformans . Reactivities of polysaccharides with seven monoclonal antibodies raised against polysaccharides of serotypes A, B, C, and D were assessed by an enzyme-linked immunosorbent assay and double immunodiffusion . The results indicated that there is heterogeneity within all four serotypes in the expression of epitopes reactive with monoclonal antibodies.

N Engl J Med, 1989 Sep 21, 321(12), 794 - 9
Infections with Cryptococcus neoformans in the acquired immunodeficiency syndrome; Chuck SL et al.; We reviewed the records of 106 patients with cryptococcal infections and the acquired immunodeficiency syndrome (AIDS) treated at San Francisco General Hospital . We examined four issues: the efficacy of treatment with amphotericin plus flucytosine as compared with amphotericin alone, the efficacy of suppressive therapy, the prognostic clinical characteristics, and the course of nonmeningeal cryptococcosis . In 48 of the 106 patients (45 percent), cryptococcosis was the first manifestation of AIDS . Among the 89 patients with cryptococcal meningitis confirmed by culture, survival did not differ significantly between those treated with amphotericin plus flucytosine (n = 49) and those treated with amphotericin alone (n = 40) . Flucytosine had to be discontinued in over half the patients because of cytopenia . Long-term suppressive therapy with either ketoconazole or amphotericin was associated with improved survival, as compared with survival in the absence of suppressive therapy (median survival, greater than or equal to 238 vs . 141 days; P less than 0.004) . The only clinical features independently associated with a shorter cumulative survival were hyponatremia and a positive culture for cryptococcus from an extrameningeal source . The 14 patients with nonmeningeal cryptococcosis had a median survival (187 days) and rate of relapse (20 percent) similar to those in the patients with meningitis (165 days and 17 percent, respectively) . From this retrospective study of cryptococcal infections in patients with AIDS we conclude that the addition of flucytosine to amphotericin neither enhances survival nor prevents relapse, but long-term suppressive therapy appears to benefit these patients.

Rev Prat, 1989 Sep 1, 39(19), 1663 - 8
{Cryptococcosis}; Dupont B; Cryptococcus neoformans is a ubiquitous encapsulated yeast present in soil . The usual contamination is by the respiratory route with ensuing dissemination in predisposed patients . Acquired immunodeficiency syndrome is the leading predisposing factor and illustrates the role of cellular immunity . Corticosteroid therapy and diseases of the reticulo-endothelial system can also encourage the disease . The most common visceral localization is the central nervous system, with meningo-encephalitis . In AIDS and severely immunocompromised patients multivisceral dissemination may occur . The organism is detected by culture, smear and/or biopsy . The serological test with detection of the cryptococcal polysaccharide capsular antigen is of great help for the diagnosis . The discovery of four serotypes of C . neoformans and of biochemical differences between serotypes has increased our knowledge of the ecology and epidemiology of the organism . Serotype A strains are the most common in both natural and clinical isolates, serotypes B and C are more prevalent in clinical isolates in tropical countries; their ecological site in nature is unknown . The disease bears a poor prognosis, especially in the most immunocompromised patients . The standard treatment is a combination of amphotericin B and flucytosine, but it can be toxic to the bone marrow . Considerable interest has arisen in new potential anticryptococcal agents currently under experimental study, such as itraconazole and fluconazole.

Rev Prat, 1989 Sep 1, 39(19), 1651 - 6
{Current role of deep mycoses in infectious pathology}; Drouhet E; Deep mycoses present new aspects characterized by deep, visceral mycotic localisations and septicemia, particularly in immunocompromised conditions . In immunodepressed patients (leukaemia, transplantation), the granulopenia descending to 500 elements/ml leads not only to invasive aspergillosis and candidosis but also to infections due to opportunistic fungi exceptionally or never seen formerly . AIDS favours opportunistic fungi related to defective cellular immunity as Cryptococcus neoformans, responsible of severe meningoencephalitis and septicemia, as Candida albicans responsible of thrush and oesophagitis, but also true pathogenic fungi (Histoplasma capsulatum) becoming opportunistic in such conditions . C . albicans provokes in heroin addicts a new septicemic syndrome with cutaneous, ocular and osteoarticular lesions and in leukaemic patients hepatic micro-abscesses soon after the neutropenic phase induced by chemotherapy . New methods for immunologic diagnosis (research of circulating fungal antigen), for clinical diagnosis (scanning, magnetic resonance) . New strategy of antifungal chemotherapy (itraconazole, fluconazole) allow to a better knowledge and control of this new infectious pathology.

DICP, 1989 Sep, 23(9), 672 - 4
Granulocytopenia and thrombocytopenia associated with combination therapy of amphotericin B and low-dose flucytosine in a patient with cryptococcal meningitis; Shindo K et al.; A patient was admitted complaining of fever and headache . He was suspected of meningitis due to nuchal rigidity, and a lumbar puncture was performed . The patient was diagnosed as having cryptococcal meningitis, as Cryptococcus neoformans was found in an India ink preparation of the cerebrospinal fluid . Both amphotericin B and low-dose flucytosine (50 mg/kg/d) were concomitantly administered to the patient and his clinical symptoms improved . However, the combination therapy induced granulocytopenia and thrombocytopenia, which resolved after discontinuance of the drugs . Amphotericin B alone failed to cause granulocytopenia or thrombocytopenia . These results suggest that the mechanisms of granulocytopenia and thrombocytopenia may be toxic reactions to flucytosine in the azotemic state caused by amphotericin B . Our report emphasizes the need for clinicians to monitor for granulocytopenia and thrombocytopenia in patients receiving treatment with both amphotericin B and flucytosine, even when flucytosine is administered in a low dose.

Kyobu Geka, 1989 Sep, 42(10), 853 - 6
{A case of primary pulmonary cryptococcosis}; Hatakeyama J et al.; A 53-year-old male was admitted because of an abnormal chest roentgenogram showing a solitary tumor shadow in the right upper lung field . Laboratory data was normal . Although examination with the bronchoscope and sputum cytology showed no abnormal findings, a partial resection of the right upper lobe was performed . Microscopic examination of the lesion was cryptococcosis . As another focus was not found by systemic examination, the lesion was disclosed primary pulmonary cryptococcosis . Cryptococcosis is rare but we must think of it when we meet a solitary tumor shadow on the chest roentgenogram.

J Ophthalmic Nurs Technol, 1989 Sep-Oct, 8(5), 189 - 92
Acquired immunodeficiency syndrome and ophthalmology; Fong AC; 1 . Ocular manifestations of AIDS are, for the most part, due to the opportunistic infections and neoplasias seen in the syndrome . 2 . Ocular infections seen in AIDS patients include cytomegalovirus, Toxoplasma gondii, Candida sp, Cryptococcus sp, herpes simplex or zoster, Mycobacterium sp, and ocular syphilis . 3 . Handwashing and disinfection of instruments are recommended to prevent transmission of infection in the ophthalmic practice.

J Comput Assist Tomogr, 1989 Sep-Oct, 13(5), 756 - 62
Dilated Virchow-Robin spaces in cryptococcal meningitis associated with AIDS: CT and MR findings; Wehn SM et al.; We present two patients with AIDS complicated by cryptococcal meningitis who displayed focal hypodense nonenhancing lesions in CT in the basal ganglia with corresponding areas of increased T2 and decreased T1 signal on magnetic resonance (MR) . These lesions corresponded precisely to the distribution of the perforating arteries . Review of pathological specimens showed these lesions to be small cystic collections of cryptococcal organisms in the perivascular spaces of the arteries with minimal or no inflammatory reaction . The cryptococcal organisms spread from the basal cisterns through the Virchow-Robin spaces, dilating these spaces, to ultimately propagate in the basal ganglia, internal capsule, thalamus, and brain stem . Such lesions have been described as characteristic for cryptococcosis in the pathology literature before the AIDS epidemic, but the radiological manifestations have not been reported previously . The changes appear characteristic for cryptococcosis, which generally incites no host response in the form of perifocal edema or enhancement . These findings in a young adult, with otherwise normal CT or MR scans, may be the first indication that the patient has AIDS . The T2-weighted image sequences are more sensitive in the detection of these lesions when compared to CT or T1-weighted MR images.

Hum Pathol, 1989 Sep, 20(9), 920 - 1
Cryptococcosis of the placenta in a woman with acquired immunodeficiency syndrome; Kida M et al.; Multiple microscopic colonies of encapsulated budding yeasts morphologically consistent with Cryptococcus sp were found in the maternal (intervillous) space of the placenta from a woman with AIDS . The patient contracted acquired immunodeficiency syndrome from her affected husband, who had died of the disease 3 years previously . The woman, who was in her sixth pregnancy at term, became symptomatic 1 month before delivery with malaise, oral thrush, and cervical lymphadenopathy . Tests for human immunodeficiency virus and serum hepatitis were negative . Cryptococcus neoformans was cultured in the blood and herpes simplex virus type II was isolated from the cervix . On the second postpartum day, the patient had difficulty breathing and died suddenly . Post-mortem examination disclosed a massive pulmonary embolus and disseminated infection with Cryptococcus organisms.

Med J Malaysia, 1989 Sep, 44(3), 194 - 8
5-Fluorocytosine resistance in clinical isolates of Cryptococcus neoformans; Chin CS et al.; Thirty six clinical isolates of Cryptococcus neoformans were tested for their susceptibility to 5-fluorocytosine and amphotericin B by the determination of minimum inhibitory concentrations and minimum fungicidal concentrations . 22.2% of the isolates were resistant to 5-fluorocytosine and 36.1% indicated 5-fluorocytosine tolerance . All strains were sensitive to amphotericin B.

Mycoses, 1989 Sep, 32(9), 448 - 54
Staib agar supplemented with a triple antibiotic combination for the detection of Cryptococcus neoformans in clinical specimens; Staib F et al.; It was demonstrated that the in vitro growth of a mucoid Escherichia coli strain from the urine of an AIDS patient could disturb the concurrent growth of Cryptococcus neoformans and the development of its brown colour effect (BCE) on Staib agar (syn . Guizotia abyssinica creatinine agar, bird seed agar, niger seed agar etc.) supplemented with penicillin + streptomycin . Owing to the supplementation with the triple antibiotic combination of penicillin + streptomycin + gentamicin and the resulting inhibition of E . coli growth, the formation of an intense BCE of the Cr . neoformans colonies after 3 d at 26 degrees C could be observed . On the same medium supplemented with this triple antibiotic combination 40 Cr . neoformans strains tested showed growth with an intense BCE after 3 d at 26 degrees C; but on Emmons' neutral Sabouraud's dextrose agar (NSDA) supplemented with the same triple antibiotic combination, inhibition of growth was found . For the examination of clinical specimens for Cr . neoformans contaminated with gram-negative rod-like bacteria, Staib agar supplemented with this triple antibiotic combination is proposed . Various antibiotic supplements to primary recovery media for fungi are discussed and ecological interrelations of bacteria and fungi are emphasized.

Rev Prat, 1989 Sep 1, 39(19), 1657 - 62
{Deep Candida and related yeast infections}; Borderon JC; Yeast-like fungi that are commonly found on the skin and in the digestive tract of healthy people may be responsible for deep infections as well as for cutaneous and mucosal diseases . Such deep infections have long been known in the case of Candida spp.; they are facilitated by immunosuppression or by factors that enable this opportunistic organism to proliferate in the gut, skin or mucosae and to penetrate into deep tissues . In addition to such well-known clinical manifestations as septicaemia and endocarditis and to pulmonary, neuromeningeal, osteo-articular and ophthalmic lesions (to be systematically searched for), and apart from the special case of chronic granulomatosis, new syndromes have been described in heroin-addicts, including syndromes with deep cranial nodules and folliculitis . The difficult diagnosis often justifies and empirical treatment in neutropenic patients . In patients with AIDS, buccal and oesophageal candidiasis is common and sometimes reveals the syndrome, but other localizations are rarely encountered . Deep manifestations in the newborn are very seldom due to contamination by the mother; they are usually iatrogenic, so that their transmission can be prevented . More recently, deep mycoses caused by other fungi beside cryptococci have been described in fragile patients . Torulopsis glabrata, Trichosporon cutaneum or even Rhodotorula spp . may penetrate through catheters or drains and cause fungaemia and septicaemia . Malassezia furfur has been found in contaminated catheters and drains and causes pulmonary infections almost exclusively in premature infants under prolonged parenteral lipid diet.

J Antimicrob Chemother, 1989 Sep, 24(3), 333 - 7
Effects of ascorbic acid on the antifungal action of amphotericin B; Brajtburg J et al.; Ascorbic acid enhanced the lethal but not the permeabilizing effects of amphotericin B on Candida albicans and Cryptococcus neoformans cells . Two other ene-diol acids, D-erythorbate and dihydroxyfumarate, also enhanced the lethal action of amphotericin B on Can . albicans . Maleic acid and gulanolactone, compounds structurally related to ascorbic acid but not containing the ene-diol group, had no such effect . It is assumed that ascorbic acid and the two other ene-diol acids acting as pro-oxidants augmented the oxidation-dependent killing of fungal cells induced by amphotericin B.

J Antimicrob Chemother, 1989 Sep, 24(3), 325 - 31
In-vitro activity of cilofungin (LY121019) in comparison with amphotericin B; Meunier F et al.; The in-vitro activity of cilofungin, a derivative of echinocandin B, was compared with that of amphotericin B in Sabouraud dextrose and Antibiotic Medium No . 3 against 100 clinical isolates of yeasts . Cilofungin appeared to be as effective, as amphotericin B against Candida albicans and yet more effective against Can . tropicalis as far as growth inhibition was concerned . Cilofungin was less active than amphotericin B against Can . (Torulopsis) glabrata and other species of Candida . It was not active against Cryptococcus neoformans . Minimum fungicidal concentrations (MFCs) of cilofungin were highly dependent on the medium, especially with Can . albicans . Low MFCs were observed in Antibiotic Medium 3 and very high MFCs were measured in Sabouraud's medium . Using a killing curve method, the initial rate of killing of amphotericin B was proportional to concentration with Can . albicans, Can . tropicalis, and Can . glabrata . With cilofungin the rate of killing was proportional to concentration only for Can . tropicalis.

Infect Immun, 1989 Sep, 57(9), 2624 - 7
Separation of chromosomes of Cryptococcus neoformans by pulsed field gel electrophoresis; Perfect JR et al.; Chromosomes from Cryptococcus neoformans, an encapsulated yeast pathogen, were separated by contour-clamped homogeneous field gel electrophoresis . Seven strains representing all four serotypes were studied . It was found that each strain had a unique, reproducible pattern of chromosome bands which could potentially be used for strain polymorphism studies . There were between 10 and 12 chromosomes in the strains studied, with an approximate genomic size of 15,000 to 17,000 kilobases . Chromosome separation also could be used to assign locations for cloned genes, and the ribosomal DNA genes were found on one of the larger C . neoformans chromosomes . The technique of electrophoretic karyotyping should be helpful for genetic and molecular investigations into the biology of C . neoformans.

Arq Neuropsiquiatr, 1989 Sep, 47(3), 326 - 31
{Cerebrospinal fluid abnormalities in 170 cases of AIDS}; Livramento JA et al.; Cerebrospinal fluid (CSF) was analysed in 170 AIDS patients . All of them showed HIV positive serological tests . All of them showed neurologic syndromes related to AIDS . The time period of the investigation was July 1984-April 1989 . In 8 cases (4.7%) CSF composition was normal . Lymphoma cells were observed in three cases . Aseptic meningities occurred in 34 cases (20.1%) . Aetiological diagnosis of associated infection was established in 88 cases: cryptococcosis in 28 (35.9%); toxoplasmosis in 20 (25.6%); syphilis in 10; candidiasis in 3; Chagas disease in 2; tuberculosis in 1; nocardiosis in 1; schistosomiasis in 1 . Antibodies for other virus were detected in 7 . Bacteria were isolated in 5 cases . Anti-HIV antibodies were tested in CSF samples of 55 cases: they were found in 48 (87.3%) . Two or more associated infections were observed in 15 cases . Changes of CSF composition in AIDS are discussed taking into account changes reported.

Nippon Kyobu Geka Gakkai Zasshi, 1989 Sep, 37(9), 1893 - 900
{A study on clinical findings and surgical treatment of pulmonary mycosis}; Yamanaka A et al.; Between 1974 and 1987, 14 patients (10 male and 4 female) underwent thoracotomy for treatment of pulmonary mycosis . They were studied on their clinical findings and surgical treatment . The median age was 48 years (range 19 to 71 years) . Fourteen cases consisted of 9 aspergillosis and 5 cryptococcosis . None of them was either debilitated or immunosuppressed before falling ill . Five of the 14 patients had other pulmonary disease and 11 had symptoms; i.e . hemoptysis or bloody sputum in 4 cases, chest pain in 3, fever in 3, cough and sputum in 2 . Nine aspergillosis consisted of 4 aspergilloma, 3 aspergillus pneumonia and 2 aspergillus empyema . Three cases of aspergillosis occurred in preexisting cavity . Five cryptococcosis consisted of 3 pseudotumorous, 1 disseminated small nodular, and 1 infiltrative types . Preoperative diagnosis was as follows; pulmonary mycosis 5, pulmonary tuberculosis 4, lung cancer 3, empyema 1 and hydropneumothorax 1 . Four patients underwent partial resection, 8 lobectomy, 1 pneumonectomy, 1 muscle prombage and thoracoplasty . The prognosis is satisfactory . All patients are alive and has no recurrence . On histopathological examination, in aspergilloma cases, invasion of aspergillus to surrounding lung tissue was not seen . In addition to well-known fact that blood-borne dissemination hardly occurred in aspergilloma in contrast to cryptococcosis . These findings suggest that aspergilloma and solitary lesion of cryptococcosis should be resected, and adjuvant chemotherapy should be accompanied for cryptococcosis.

Rev Inst Med Trop Sao Paulo, 1989 Sep-Oct, 31(5), 346 - 50
{In vitro susceptibility of Cryptococcus strains to 5 antifungal drugs}; Bava AJ et al.; A comparative study of the "in vitro" susceptibility of 24 Cryptococcus strains to 5 antifungal drugs (amphotericin B, 5 fluorocytosine, miconazole, itraconazole and ketoconazole), was carried out . These strains were grouped according to species, varieties and isolation's origins . The minimum inhibitory concentration (M.I.C.) was determined by the agar dilution technique in yeast nitrogen base agar with dextrose . The mean geometrical of the M.I.C . values of each group was compared with the others . The results obtained were homogeneous with the only exception of the "non neoformans" strains, in which, higher M.I.C . to 5 fluorocytosine values were detected.

Rev Prat, 1989 Sep 1, 39(19), 1688 - 94
{Treatment of mycoses and new antifungal agents}; Dupont B; The multiplication of iatrogenic factors, nosocomial diseases and acquired immunodeficiency syndrome is responsible for an ever increasing number of deep opportunistic mycoses, namely candidiasis, aspergillosis and cryptococcosis . The advent of a wide variety of rare opportunistic fungi is a fairly recent and worrying phenomenon . To combat these infections, often very serious, our therapeutic armentarium is rather scanty . Moreover, the prescription of the available drugs is limited by their toxicity, their spectrum and their route of administration or by the emergence under treatment of resistant mutants . Beside old products, such as amphotericin B and 5-fluorocytosine, miconazole and, mainly ketoconazole (both azole derivatives) were the first steps towards oral administration and low toxicity . Fluconazole is a triazole antifungal compound with a very original distribution to the meninges and urinary tract; it is mainly used in candidiasis and cryptococcosis . Another triazole compound, itraconazole, presents the particularity of being active against Aspergillus spp., Cryptococcus spp . and some agents of exotic mycoses . These two products are well tolerated and should soon be available for use in deep visceral mycoses . Other azole derivatives are under study . Among compounds issued from new chemical families, terbinafine (allylamine) is particularly active against dermatophytes, and cilofungine (a polypeptide) against fungi . These drugs are in the experimental stage . Research should be pursued aimed at developing, probably in new chemical families, and agent that is fungicidal in vivo.

Kansenshogaku Zasshi, 1989 Sep, 63(9), 1047 - 52
{A case of adult T-cell leukemia with pulmonary cryptococcosis, cryptococcal meningitis and Pneumocystis carinii pneumonia}; Shigeno H et al.; A 66-year-old woman was admitted to the Medical College Hospital of Oita on February 23, 1988, because of headache and fever . Chest X-P and chest CT findings showed a coin lesion in r-S4 . Cryptococcus neoformans was isolated from the CSF . Abnormal lymphocytes with lobulated nuclei were found in 0-5% of peripheral leukocytes . The ATLA-antibody was positive and bone marrow smear showed normal myelogram . According to these data, we diagnosed the patient as smouldering adult T-cell leukemia accompanied with pulmonary cryptococcosis and cryptococcal meningitis . C . neoformans disappeared from the CSF and cryptococcal antigen was not detectable after Amphotericin B and Flucytosine treatment . On April 1, the patient complained of a dry cough, high fever and dyspnea . A chest X-ray showed bilateral patchy infiltrations . By the methenamine silver staining, cysts of Pneumocystis carinii were found in the specimens of transbronchial lung biopsy and bronchoalveolar lavage fluid . The abnormal shadow on chest X-ray disappeared after TMP-SMX and aerosolised pentamidine treatment.

Kansenshogaku Zasshi, 1989 Sep, 63(9), 1033 - 7
{An autopsied case of disseminated cryptococcosis with marked lymphadenopathy}; Sasayama K et al.; A 75 year old woman who was admitted to Higashisaga National Hospital due to chronic bronchitis showed a high fever (39.2 degrees C) and marked lymphadenopathy of the bilateral inguinal lymph-nodes . Chest X-ray showed diffuse infiltration . Cryptococcus was detected in biopsied lymph-nodes . Although 5-fluorocytosine, miconazole, amphotericin-B were administered for six weeks, she died and an autopsy was performed . Disseminated cryptococcosis was observed in the lung, liver, spleen, kidney, bone marrow, and lymph-nodes of the lung hilum, paratrachea, retroperitoneum, gall bladder and groin . She was a human T cell leukemia type I (HTLV-I) carrier, and this could be related to disseminated cryptococcosis.

Ann Ig, 1989 Sep-Oct, 1(5), 1057 - 66
{AIDS in Africa}; Sansone R et al.; PIP: In regard to AIDS, attention has focused on Africa for the following reasons: 1) Solid evidence indicates that antibodies against HIV were present in African sera collected in the early 1960s . 2) Up to 1986, AIDS epidemiology was hampered by inconsistent demographic data, inadequate public health services, and scanty laboratory evidence . 3) Prevalent infection routes in Africa are not entirely overlapping with Western countries . 4) Clinical aspects of AIDS progression in Africa appear linked to the different opportunistic agents and to the prevailing hygienic and social conditions . In 1983, in Rwanda and Zaire, the annual incidence of HIV infection ranged from 17 to 800/million and 170/ million, respectively . In the first five months of 1985, the range of annual incidence in Africa was 50-1000/million . In Zaire, the male-female infection ratio was 1:1.2 and the average age of infected people was 33.6 years . Seropositivity ranged from 1% to 15% . The distribution of African AIDS is characterized by heterosexual transmission, transmission via contaminated syringes, blood transfusion, and maternal-fetal transmission . Lack of condom use among prostitutes and multiple partners are the main routes of heterosexual transmission . Other routes are high risk sexual practices as well as traditional and tribal rituals (clitoridectomy/female genital mutilation) . Perinatal infection results from maternal-fetal transmission but also from blood transfusion and the use of unsterilized syringes . In 1986, in Zaire, among 2384 hospital workers, significantly more seropositivity occurred in a group who had had injections in the previous three years . A 1986 study also hinted at the possible role of insects in HIV infection . The major symptoms of AIDS in an African context, in addition to the usual depletion of CD4 lymphocytes, include diarrhea and weight loss, candida, cryptococcus, cytomegalovirus, cryptosporidium, and herpes simplex . Only 14% of AIDS patients in Africa have pneumonia carinii as compared with 63% of AIDS patients in Europe . The concomitant infection with both HIV and tuberculosis is particularly high in Africa .

Wien Med Wochenschr, 1989 Aug 31, 139(15-16), 370 - 4
{Interaction studies with fluconazole, a new triazole antifungal drug}; Rieth H et al.; Fluconazole is a new systemic antifungal agent from the class of triazoles . Its efficacy was documented in clinical studies of patients with candidosis and cryptococcosis . Due to the influence on human cytochrome-P-450-dependent enzymes, special attention should be paid, in the development of new antifungal agents, to the inhibition of the metabolization of other simultaneously given substances and to the inhibition of steroid hormone synthesis in the gonads and adrenal glands . The interaction studies carried out with frequently administered drugs such as oral contraceptives, cimetidine, warfarin, tolbutamide, and cyclosporin (transplantation patients) allow the concomitant intake of these substances with fluconazole . Concomitant anti-coagulant treatment requires a precautionary monitoring of prothrombin time; it may be necessary in individual cases to reduce the anticoagulant dosage . The intake of oral hypoglycemics of the tolbutamide type requires monitoring of blood glucose, although blood glucose lowering effects were not found . One interaction study carried out with phenazone showed the low metabolization tendency of fluconazole . Approximately 80% of the administered fluconazole dose appeared in the urine unchanged . Studies in male and female subjects with multiple doses of fluconazole (4 weeks) did not show any significant effects on the endocrinology and steroid synthesis in man.

Scott Med J, 1989 Aug, 34(4), 494 - 6
Fungal peritonitis in children on continuous ambulatory peritoneal dialysis; Mocan H et al.; Between 1979 and 1985, six of 26 patients undergoing continuous ambulatory peritoneal dialysis developed fungal peritonitis . All had received antibacterial therapy with cefamandole and/or netilmicin prior to the diagnosis . The causal organisms were Candida albicans (three), Candida glabrata (one), Cryptococcus laurentii (one) and Saccharomyces cerevisiae (one) . Treatment comprised catheter removal preceded by antifungal drugs (flucytosine and/or amphotericin B) in four patients and catheter removal alone in two . All patients were transferred to haemodialysis and five of the six developed extensive intra-abdominal adhesions . The most prudent management of fungal peritonitis in children would seem to be early cannula removal.

Arch Intern Med, 1989 Aug, 149(8), 1875 - 7
HIV-2-associated AIDS in the United States . The first case; Kloser PC et al.; A 41-year-old woman from the Cape Verde Islands, Africa, who had been residing in the United States for 11 months was found to have human immunodeficiency virus type 2 (HIV-2)-associated acquired immunodeficiency syndrome (AIDS) . Antibody to HIV-2 was found by enzyme immunoassay and was verified by radioimmunoprecipitation . The patient was being treated for pulmonary tuberculosis at the time of her admission to our institution . Further laboratory and clinical evaluation at our facility revealed depressed CD4 lymphocytes, oral candidiasis, and cryptococcal meningitis with indeterminate results on serologic testing for HIV type 1 (HIV-1) . The biopsy specimen of a lesion in the right occipital lobe of the brain documented Toxoplasma gondii, indicating a clinical diagnosis of AIDS . To our knowledge, our study presents the first known patient with HIV-2-associated AIDS in the United States . Our patient provides further evidence that HIV-2 causes severe immunodeficiency and opportunistic infection . The condition should be suspected in the face of normal or repeatedly equivocal HIV-1 antibody test results in the presence of clinically documented AIDS.

Chest, 1989 Aug, 96(2), 440 - 1
Pleural effusion as the initial manifestation of disseminated cryptococcosis in acquired immune deficiency syndrome . Diagnosis by pleural biopsy; Katz AS et al.; Pleural effusion is an unusual presentation of cryptococcal infection in the acquired immune deficiency syndrome . Previous investigators have established the diagnosis of cryptococcal pleural disease by culturing pleural fluid, bronchial washings, and extrapulmonary sources . We report the first case of cryptococcal pleural effusion proved by closed pleural biopsy . Pleural biopsy may be an effective and rapid method of determining the etiology of pleural effusion in the acquired immune deficiency syndrome.

Acta Stomatol Belg, 1989 Aug, 86(2), 87 - 140
{General review of mycoses affecting the maxillofacial area}; Piette EM; It is interesting and useful to review the different mycoses which can affect oral and maxillofacial tissues . In this review, all mycoses which can involve these tissues are described, based on a simple classification into superficial and deep mycoses . The superficial mycoses described are the dermatophytoses, Tinea, the piedra, but also the candidiasis, which are superficial opportunistic infections . The deep mycoses are subdivided into subcutaneous, systemic, and opportunistic mycoses . Subcutaneous fungal infections are sporotrichosis, lobomycosis, rhinosporidiosis, entomophthoromycosis, and chromomycosis . Systemic fungal infections are paracoccidioidomycosis, blastomycosis, cryptococcosis, histoplasmosis, histoplasmosis duboisii, and coccidioidomycosis . Opportunistic mycoses are aspergillosis, mucormycosis, geotrichosis, torulopsosis (considered nowadays as a candidiasis), basidiomycosis, cephalosporiomycosis, alternariosis, cercosporomycosis, paecilomycosis, and fusariomycosis . Eumycotic mycetomas are also cited.

J Cardiovasc Nurs, 1989 Aug, 3(4), 65 - 76
AIDS-related heart disease: a review of the literature; Nyamathi A; Heart disease related to the acquired immunodeficiency syndrome (AIDS) encompasses a number of pathologic findings that may or may not be associated with specific cardiac signs and symptoms . A review of 30 reports revealed that cardiac disorders were apparent in 424 (74%) of 574 AIDS patients . Neoplasms and opportunistic infections each were reported in 46 (8%) patients . The area of the heart most commonly affected was the myocardium . Pericardial disease as a single disorder was apparent in 14 patients, the etiologic bases of which were Mycobacterium tuberculosis . Cryptococcus neoformans infection, and unspecified fibrinous pericarditis . Endocardial disease was histologically evident in 18 patients with nonbacterial thrombotic endocarditis, and one patient was found to have Nocardia asteroides endocarditis . Although cardiac symptoms (dyspnea and chest pains); signs (pulsus paradoxus and murmurs); or ECG, roentgenogram, or echocardiographic manifestations of AIDS may be significant, they are not generally helpful in establishing a clinical diagnosis . Echocardiograms and a heightened degree of clinical suspicion have proven useful in detecting cardiac dysfunction and life-threatening cardiac tamponade.

Zhonghua Wai Ke Za Zhi, 1989 Aug, 27(8), 472 - 3, 509
{Cryptococcal granuloma of the brain . Report of 7 cases}; Li ND; 7 cases of cryptococcal granuloma of the brain are reported . All were confirmed pathologically by autopsy or operation . The granuloma involved not only cerebral hemisphere but also the basal ganglion, hypothalamus, cerebellum and brain stem . It's clinical character and CSF examination are closely similar to the findings of tuberculous meningitis, and the larger toruloma is easy to be mistaken as brain tumor . The authors introduced several valuable methods of diagnosis of these patients . The indications of operation as well as medication are discussed also.

Acta Stomatol Belg, 1989 Aug, 86(2), 87 - 140
{General review of maxillofacial mycoses}; Piette EM; It is interesting and useful to review the different mycoses which can affect oral and maxillofacial tissues . In this review, all mycoses which can involve these tissues are described, based on a simple classification into superficial and deep mycoses . The superficial mycoses described are the dermatophytoses, the Tineas, the piedras, but also the candidoses, which are superficial opportunistic infections . The deep mycoses are subdivided into subcutaneous, systemic, and opportunistic mycoses . Subcutaneous fungal infections are sporotrichosis, lobomycosis, rhinosporidiosis, entomophtoromycoses, and chromomycoses . Systemic fungal infections are paracoccidioidomycosis, blastomycosis, cryptococcosis, histoplasmosis, histoplasmosis duboisii, and coccidioidomycosis . Opportunistic mycoses are aspergillosis, mucormycosis, geotrichosis, torulopsosis (considered nowadays as a candidosis), basidiomycosis, cephalosporiomycosis, alternariosis, cercosporomycosis, paecilomycosis, and fusariomycosis . Eumycotic mycetomas are also cited.

Antimicrob Agents Chemother, 1989 Aug, 33(8), 1242 - 6
Efficacy of SCH39304 in murine cryptococcosis; Restrepo BI et al.; Cryptococcal meningitis is increasing in frequency, in large part because of the advent of acquired immune deficiency syndrome . Using the murine cryptococcosis model, a new oral triazole, SCH39304, has been compared with two drugs in clinical use, fluconazole and amphotericin B . BALB/c mice (nu/nu and nu/+) were challenged intracerebrally or intranasally . Oral treatment was given daily with SCH39304 at doses of 1 to 60 mg/kg of body weight or fluconazole at doses of 1 or 5 mg/kg of body weight . Amphotericin B was given intraperitoneally three times weekly, at doses of 3 or 6 mg/kg . After intracerebral challenge, SCH39304 prolonged survival in doses as low as 1 mg/kg, a dose at which fluconazole was ineffective . At equal doses, SCH39304 consistently increased survival more than did fluconazole but not longer than did amphotericin B . SCH39304 significantly lowered colony counts in brains more than did fluconazole but no more than did amphotericin B . SCH39304 was also superior to fluconazole after intranasal challenge at equal doses . SCH39304 appears to be superior to fluconazole in mice when the drugs are given at equal doses . Clinical trials are warranted.

Ann Intern Med, 1989 Aug 1, 111(3), 223 - 31
CD4 counts as predictors of opportunistic pneumonias in human immunodeficiency virus (HIV) infection; Masur H et al.; STUDY OBJECTIVE: To determine if circulating CD4+ lymphocyte counts are predictive of specific infectious or neoplastic processes causing pulmonary dysfunction . DESIGN: Retrospective, consecutive sample study . SETTING: Referral-based clinic and wards . PATIENTS: We studied 100 patients infected with human immunodeficiency virus (HIV) who had had 119 episodes of pulmonary dysfunction within 60 days after CD4 lymphocyte determinations . MEASUREMENTS AND MAIN RESULTS: Circulating CD4 counts were less than 0.200 X 10(9) cells/L (200 cells/mm3) before 46 of 49 episodes of pneumocystis pneumonia, 8 of 8 episodes of cytomegalovirus pneumonia, and 7 of 7 episodes and 19 of 21 episodes of infection with Cryptococcus neoformans and Mycobacterium avium-intracellulare, respectively . In contrast, circulating CD4 counts before episodes of nonspecific interstitial pneumonia were quite variable: Of 41 episodes, 11 occurred when CD4 counts were greater than 0.200 X 10(9) cells/L . The percent of circulating lymphocytes that were CD4+ had a predictive value equal to that of CD4 counts . Serum p24 antigen levels had no predictive value . CONCLUSIONS: Pneumocystis pneumonia, cytomegalovirus pneumonia, and pulmonary infection caused by C . neoformans or M . avium-intracellulare are unlikely to occur in HIV-infected patients who have had a CD4 count above 0.200 to 0.250 X 10(9) cells/L (200 to 250 cells/mm3) or a CD4 percent above 20% to 25% in the 60 days before pulmonary evaluation . Patients infected with HIV who have a CD4 count below 0.200 X 10(9) cells/L (or less than 20% CD4 cells) are especially likely to benefit from antipneumocystis prophylaxis.

Zhonghua Min Guo Wei Sheng Wu Ji Mian Yi Xue Za Zhi, 1989 Aug, 22(3), 173 - 80
Detection of mycobacterial antigens in cerebrospinal fluid by enzyme-linked immunosorbent assay utilizing anti-mycobacterial saline extract antibodies; Wu CH et al.; Using anti-mycobacterial saline extract antibodies, Mycobacterium tuberculosis antigens can be detected in cerebrospinal fluid by a highly specific and sensitive double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) . The ELISA was dose-dependent and capable of detecting as little as 6.0 ng of antigens . Specificity was demonstrated by negative results (0.063 +/- 0.008) with other bacterial and cryptococcal antigens (n = 9), and maximum cross-reactivity with other mycobacteria was less than 2.0% . Absorbance for six patients with confirmed tuberculous meningitis gave results ranging from 0.168 to 0.898 with a mean value of 0.393 +/- 0.248 . For 172 nonmeningitis and nontuberculosis control patients and 6 treated tuberculous meningitis patients, optical densities were 0.064 +/- 0.001 and 0.057 +/- 0.007, respectively . Significant statistical difference (p less than 0.001) was found between the tuberculous meningitis and control groups.

J Med Assoc Thai, 1989 Aug, 72(8), 436 - 40
Diagnosis of systemic candidosis by immunodiffusion test with locally prepared antigen; Srimuang S et al.; Locally-made C . albicans, C . tropicalis, C . krusei antigens and antisera were made and compared with reference C . albicans and C . krusei antigens and antisera from the Center for Disease Control (CDC), Atlanta, Georgia, U.S.A., and the Provincial Laboratory of Public Health, University of Alberta, Edmonton, Alberta, Canada, respectively . The local antigens and antisera showed 3 precipitin bands when reacted with locally-made and reference antisera . When tested with human sera from 171 normal persons (aged 17-24 years), 30 Candida vaginitis, 30 Candida balanitis, 30 mucocutaneous candidosis, 30 pityriasis versicolor and 10 aspergillosis patients revealed no precipitin band . When tested with cryptococcosis, 2 out of 6 sera showed a precipitin band but only at 1:1 dilution . Four candidosis sera offered by CDC showed precipitin bands at dilutions up to 1:4 . Three Thai candidosis sera also showed precipitin bands at dilutions up to 1:2 . Therefore, we judged the baseline titer for Thai population to be 1:2.

Parassitologia, 1989 Aug-Dec, 31(2-3), 207 - 12
{Presence of pathogenic yeasts in the feces of the semi-domesticated pigeon (Columba livia, Gmelin 1789, urban type) from the city of Turin}; Gallo MG et al.; The results of a survey on the presence of pathogenic yeasts in pigeon droppings collected in Turin, are shown . The study was carried out in 8 densely populated areas, where human-animal contact is highest . A total of 427 pigeon dropping samples, most of which fresh, were collected . 550 yeast colonies, clinically interesting or at least pathologically significant, were isolated by the identification routine methods . The yeasts belong to the following species: Candida albicans, C . humicola, C . krusei, C . guillermondii, C . lypolitica, C . lambica, C . parapsilosis, C . tropicalis, C . rugosa, C . zeylanoides, Cryptococcus albidus, C . laurentii, C . neoformans, Hansenula anomala, Geotrichum sp., Kloekera apiculata, Rhodotorula glutinis, R . rubra, Saccharomyces cerevisiae, Torulopsis candida, T . glabrata, Trichosporon beigelii, T . capitatum, T . cutaneum, T . pullulans.

Ann Intern Med, 1989 Jul 15, 111(2), 125 - 8
Persistent Cryptococcus neoformans infection of the prostate after successful treatment of meningitis . California Collaborative Treatment Group; Larsen RA et al.; STUDY OBJECTIVE: To assess the frequency of persistent Cryptococcus neoformans infection in patients with the acquired immunodeficiency syndrome (AIDS) after receiving apparently adequate treatment for meningitis . DESIGN: Blood, urine, and cerebrospinal fluid were cultured at the conclusion of primary therapy to assess the adequacy of treatment . SETTING: Outpatient clinics at three medical centers . PATIENTS: Patients had C . neoformans grown in culture from cerebrospinal fluid . Primary therapy consisted of either 2.0 g of amphotericin B alone; 6 weeks of combination therapy with flucytosine; or, if flucytosine was poorly tolerated, an adjusted minimum total amphotericin B dose . To meet criteria for adequate treatment of meningitis all patients had two sequential cerebrospinal fluid samples which were culture negative . MEASUREMENTS AND MAIN RESULTS: Nine of forty-one patients grew C . neoformans from urine after completion of primary treatment, but none had urinary symptoms . Fungi were visualized in expressed prostatic secretions in 4 of these patients . One patient refused further treatment and developed cryptococcemia within 5 weeks . Three patients received additional amphotericin B; all had persistent funguria without systemic relapse . Six patients received fluconazole; 4 became urine culture negative, and 2 had systemic relapse . CONCLUSION: The persistence of urinary C . neoformans after adequate therapy for meningitis suggests that the urinary tract (probably the prostate) is a sequestered reservoir of infection from which systemic relapse may occur.

Nihon Kyobu Shikkan Gakkai Zasshi, 1989 Jul, 27(7), 825 - 8
{A case of primary pulmonary cryptococcosis showing spontaneous recovery}; Homma S et al.; A 37-year-old woman was admitted with fever and cough . The chest roentgenogram revealed a solitary large round mass in the right lower lung field . Diagnosis was made by transbronchial lung biopsy . There was no evidence of abnormal cell-mediated immunity . The patient made an uneventful recovery and the chest X-ray showed progressive clearing without specific therapy . After 6 months, the mass lesion disappeared . This case suggests that specific therapy may not be necessary for all cases of primary pulmonary cryptococcosis.

FEMS Microbiol Lett, 1989 Jul 1, 51(1), 107 - 11
An NADH:Fe(III)EDTA oxidoreductase from Cryptococcus albidus: an enzyme involved in ethylene production in vivo?
Fukuda H, Takahashi M, Fujii T, Tazaki M, Ogawa T.
An ethylene-forming enzyme which forms ethylene from 2-oxo-4-methylthiobutyric acid (KMBA) was purified to an electrophoretically homogeneous state from a cell-free extract of Cryptococcus albidus IFP 0939 . The presence of KMBA, NADH, Fe(III) chelated to EDTA and oxygen were essential for the formation of ethylene . When ferric ions, as Fe(III)EDTA, in the reaction mixture were replaced by Fe(II)EDTA under aerobic conditions, the non-enzymatic formation of ethylene was observed . Under anaerobic conditions in the presence of Fe(III)EDTA and NADH, the enzyme reduced 2 mol of Fe(III) with 1 mol of NADH to give 2 mol of Fe(II) and 1 mol NAD+, indicating that the ethylene-forming enzyme is an NADH-Fe(III)EDTA oxidoreductase . The role of NADH:Fe(III)EDTA oxidoreductase activity in the formation in vivo ethylene from KMBA is discussed.

Neurosurgery, 1989 Jul, 25(1), 44 - 7; discussion 47-8
Neurosurgical aspects of cerebral cryptococcosis; Chan KH et al.; Eleven patients with raised intracranial pressure caused by cerebral cryptococcosis developed complications requiring neurosurgical operations . Two patients were fully conscious on admission, and 9 had impaired consciousness, four of whom were comatose . Seven patients were found to have hydrocephalus only . Two patients had cerebral edema initially, and 2 had cystic lesions . One of the latter developed subdural effusion . All patients eventually developed progressive hydrocephalus requiring placement of a ventriculoperitoneal shunt . Four patients were initially treated by external ventricular drainage . When external ventricular drainage was used initially, there were no associated complications; however, there was a high incidence of complications (4 of 7 patients) when a ventriculoperitoneal shunt was placed as the initial treatment . Of the 11 patients, 10 (91%) survived; of these 9 (82%) made an excellent recovery and 7 (64%) returned to their original work . The patient who died had been receiving steroid therapy for hypopituitarism.

Diagn Microbiol Infect Dis, 1989 Jul-Aug, 12(4 Suppl), 221S - 228S
Fungal infections in the immunocompromised host; Stein DK et al.; With the increased number of immunocompromised patients there has been a concomitant increase in patient morbidity and mortality due to fungi . The etiologic microorganisms vary depending upon the type of immune dysfunction . Patients with malignancies and chemotherapy-induced neutropenia commonly are infected with Candida and Aspergillus . Other ubiquitous fungi such as Rhizopus, Fusarium, and Trichosporon are more frequently implicated as agents of disease in these patients . Patients with cell-mediated immune dysfunction such as acquired immune deficiency syndrome (AIDS) are susceptible to mucocutaneous candidiasis and pulmonary and disseminated cryptococcosis . Histoplasmosis and coccidioidomycosis have been particularly lethal infections in AIDS patients . Contributing factors such as broad-spectrum antibiotic use, intravenous catheterization, malnutrition, hyperalimentation, multiple surgical procedures and/or trauma, and steroids used either singly or in combination may also predispose patients to invasive fungal disease . Definitive diagnosis is often difficult to establish and usually requires invasive biopsy . Delay of culture results due to the time required to process specimens and to allow the fungus to grow also contributes to the poor results of therapy . Biopsy of skin lesions represents a useful technique for making a diagnosis . Recent advances in antifungal therapeutics promise to change the current approach to treatment for several of the mycoses . The availability of new oral azoles with spectra of activity that include aspergillosis and cryptococcosis, which currently require treatment with parenteral amphotericin B, may prove practical for prolonged oral therapy of otherwise lethal mycoses.

J Med Microbiol, 1989 Jul, 29(3), 189 - 94
Coagglutination (COA) test for the rapid diagnosis of cryptococcal meningitis; Koshi G et al.; Cryptococcus coagglutination (COA) test reagent was prepared locally and showed no cross reactions with different species of bacteria or yeasts or with 75 control sera including 25 that gave positive results for RA factor . We used the COA test to detect cryptococcus antigen in the CSF and we could confirm the diagnosis of 11 out of 115 suspected cases of fungal meningitis; the titre varied from 4 to 128 . A four-fold rise in titre confirmed the diagnostic value and a steady fall in titre in three patients on therapy indicated the prognostic value of the test . The earliest confirmation was in a renal transplant patient on the eighth day after onset of symptoms . The COA test was negative with the CSF of 118 patients with chronic meningitis . Cryptococcal colony forming units (cfu) in CSF varied from 100 to greater than 100,000/ml and correlated well with microscopy and with the COA antigen titre in CSF . Four out of the 11 patients who had cryptococcaemia, had 50,000-100,000 cfu/ml in the CSF . Cryptococcus antigen was detected by COA in the serum of all 11 patients, even in those with only 100 cfu/ml in CSF . In the three post-renal transplant patients, who were being monitored regularly, the diagnosis was made early and all three recovered on antifungal therapy with no relapse to date (1-2 years) . All the others, including the two primary CNS infections, succumbed to the disease because they presented late for diagnosis and therapy . The cryptococcus COA test is a simple and specific test that can be used as a rapid test to confirm early diagnosis and permit prompt therapy, which should improve the prognosis in CNS and other forms of systemic cryptococcosis . Moreover, it is reproducible and cost-effective, particularly in countries where the latex and other expensive test reagents are not generally available.

Infect Immun, 1989 Jul, 57(7), 1990 - 7
Murine natural killer cell interactions with a fungal target, Cryptococcus neoformans; Hidore MR et al.; Earlier investigations have shown that murine natural killer (NK) cells bind to and inhibit the growth of the fungal pathogen Cryptococcus neoformans in vitro and in vivo . To define the stages of NK cell-mediated inhibition of C . neoformans growth and the requirements for the completion of these stages, the events which lead to cryptococcal growth inhibition were compared with those previously elucidated for NK cell-mediated tumor cell lysis . Our data indicate that NK cell-cryptococci binding is a distinct event that precedes inhibition; is temperature independent, although it is slowed at 4 degrees C; and is Mg2+ dependent . In contrast to binding, NK cell-mediated cryptococcal growth inhibition is temperature, Mg2+, and Ca2+ dependent . The removal of Ca2+ by EDTA addition within 3 h after maximal NK cell-cryptococci binding significantly reduced cryptococcal growth inhibition, indicating that Ca2+ is required either late in the NK cell trigger stage or early in the inhibitory stage . These stages and requirements are similar to those previously demonstrated for the model of NK cell-mediated tumor cell lysis; however, the NK cell-cryptococci interactions are somewhat slower than the interactions which culminate in the lysis of the YAC-1 tumor cell targets . These results suggest that C . neoformans cells, although structurally distinct from the standard tumor cell targets, are capable of similar cell-to-cell interactions with NK effector cells as the tumor cell targets.

Diagn Microbiol Infect Dis, 1989 Jul-Aug, 12(4 Suppl), 239S - 247S
A clinical study of fluconazole for the treatment of deep mycoses; Ikemoto H; A multicenter clinical study of fluconazole was conducted at 41 hospital sites in Japan . Fluconazole was administered orally or intravenously at daily doses of 50 to 400 mg to 199 patients with deep-seated mycoses . Clinical efficacy was evaluable in 125 of these patients . Most cases were complicated with serious underlying diseases such as cancer, leukemia, or AIDS . Clinical cures were achieved in 56 (87.5%) of 64 cases of candidiasis, in 11 (68.8%) of 16 cases of cryptococcosis, in 19 (44.2%) of 43 cases of aspergillosis, and in one case each (100%) of mucormycosis and fungemia due to an unspecified yeast . Eradication rates of causative fungi were 87.9% in Candida spp., 62.5% in Cryptococcus neoformans, and 52.2% in Aspergillus spp . Side effects were observed in 13 cases, with an incidence rate of 6.5% . In most cases fluconazole was well tolerated . Changes in laboratory test values due to the drug were reported in 35 patients with an incidence rate of 17.6% . The changes were minor and transient; primarily increases in liver enzyme . Fluconazole is a useful antifungal agent for the treatment of systemic deep-seated mycoses.

Diagn Microbiol Infect Dis, 1989 Jul-Aug, 12(4 Suppl), 235S - 238S
Efficacy of fluconazole in cryptococcal meningitis; Jones PD et al.; In this clinical trial, oral fluconazole was used to treat cryptococcal meningitis in 32 patients with Acquired Immune Deficiency Syndrome (AIDS) . In 11 patients who received 200 to 400 mg/day of fluconazole as primary therapy, a favorable clinical response was obtained in 67% of all evaluable patients . A negative cerebrospinal fluid (CSF) culture was also reported for 86% of these cases . Fluconazole was used as second-line therapy in an additional 15 patients who were not responsive to therapy with amphotericin B or amphotericin B combined with flucytosine . Positive clinical and mycologic responses were then obtained in more than 60% of these cases . Following successful treatment with fluconazole as either the primary or secondary antifungal agent, 26 patients were evaluated during maintenance therapy with 100 to 200 mg daily of fluconazole to prevent recurrence of disease . The relapse rate was 3.2 cases of cryptococcal meningitis per 1000 patient weeks, with a mean duration of 22 weeks for maintenance therapy . An additional six patients who were also treated with either amphotericin B alone or in combination with flucytosine but were asymptomatic or CSF culture negative when treatment with fluconazole was initiated were evaluated for the safety and efficacy of maintenance therapy . Thus, treatment of fluconazole appears to be efficacious as well as safe . The incidence of superimposed infections associated in these AIDS patients make it difficult to accurately assess any adverse effects.

Diagn Microbiol Infect Dis, 1989 Jul-Aug, 12(4 Suppl), 229S - 233S
Review of fluconazole: a new triazole antifungal agent; Washton H; Fluconazole is a new triazole antifungal agent with unique pharmacokinetic properties . It can be administered orally or parenterally and achieves rapid distribution by either route, and its absorption is not affected by the presence of food . It has a plasma half-life of approximately 25-30 hr and approximately 70% of dose is excreted in the urine unchanged . There is linearity of fluconazole plasma concentrations over the dose range and the elimination rate is independent of dose . No effect has been seen on basal or ACTH-stimulated cortisol or on testosterone, estrogen, progesterone, or other steroid hormones, and there is no interaction with an oral contraceptive . No interaction with concomitantly administered cyclosporine has been documented, and there are no clinically significant differences in absorption when fluconazole is given in the presence or absence of cimetidine or food . Patients who are concomitantly receiving coumarin anticoagulants should be monitored because there is an interaction between fluconazole and such anticoagulants . Patients taking oral hypoglycemics and fluconazole should be monitored, because fluconazole has been shown to inhibit the metabolism of tolbutamide . Fluconazole has been successfully used to treat a variety of fungal infections in a variety of contexts including vaginal candidiasis; oropharyngeal candidiasis in immunocompromised patients, those with malignancies, transplant recipients, and patients with systemic sclerosis; patients with cryptococcal meningitis; and patients with fungal infections who were also treated with chemotherapy or radiation therapy . In the treatment of all of these infections with doses ranging from 50 mg to 400 mg a day of fluconazole, there has been a very low incidence of side effects (9.3%) reported, and only 1.1% of all patients were withdrawn from therapy.

Ophthalmology, 1989 Jul, 96(7), 1092 - 9
Ocular manifestations of acquired immune deficiency syndrome; Jabs DA et al.; The ocular complications of acquired immune deficiency syndrome (AIDS) include: (1) a noninfectious microangiopathy, most often seen in the retina, consisting of cotton-wool spots with or without intraretinal hemorrhages and other microvascular abnormalities; (2) opportunistic ocular infections, primarily cytomegalovirus (CMV) retinitis; (3) conjunctival, eyelid, or orbital involvement by those neoplasms seen in patients with AIDS (i.e., Kaposi's sarcoma and lymphoma); and (4) neuro-ophthalmic lesions . In a series of 200 AIDS patients evaluated clinically, AIDS retinopathy was present in 66.5% . Sixty-four percent had cotton-wool spots, and 12% had intraretinal hemorrhages . Cytomegalovirus retinitis was diagnosed in 28% of AIDS patients . Neuro-ophthalmic lesions were found in 8% of all AIDS patients and were present in 33% of those patients with cryptococcal meningitis . Acquired immune deficiency syndrome retinopathy was present in 40% of 35 patients with the AIDS-related complex (ARC) and in 1.3% of 232 patients with asymptomatic human immunodeficiency virus (HIV) infection, evaluated photographically . These results suggest that the prevalence of AIDS retinopathy increases with increasing severity of HIV infection, and that CMV retinitis presents a significant vision-threatening problem in AIDS patients.

Infect Immun, 1989 Jul, 57(7), 1922 - 7
Activation and binding of opsonic fragments of C3 on encapsulated Cryptococcus neoformans by using an alternative complement pathway reconstituted from six isolated proteins; Kozel TR et al.; Encapsulated Cryptococcus neoformans yeast cells are potent activators of the complement system . We examined the interaction of the yeast cells with an alternative complement pathway reconstituted from isolated factor D, factor B, factor H, factor I, C3, and properdin . Incubation of encapsulated cryptococci with the reconstituted pathway led to activation and binding of C3 fragments to the yeast cells that was quantitatively and qualitatively identical to that observed with normal human serum . Incubation with either normal serum or a mixture of isolated proteins led to binding of 4 x 10(7) to 5 x 10(7) C3 molecules to the yeast cells . The kinetics for activation and binding of C3 were identical, with maximum binding observed after a 20-min incubation . Immunoglobulin G was not needed for optimal activation kinetics . C3 fragments eluted from the yeast cells by treatment with hydroxylamine and subsequent analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated the presence primarily of iC3b on yeast cells incubated with either normal serum or the reconstituted pathway . Ultrastructural examination of the opsonized yeast cells showed that the cryptococcal capsule was the site for binding of C3 activated from normal serum or the reconstituted pathway, with a dense accumulation of C3 at the periphery of the capsule . Thus, incubation of encapsulated cryptococci in the reconstituted pathway led to deposition of opsonic complement fragments at a site that was appropriate for interaction with phagocyte receptors . Cryptococci opsonized with the reconstituted pathway showed a markedly enhanced interaction with cultured human monocytes compared with unopsonized yeast cells, indicating that the alternative pathway alone is opsonic for yeast cells . However, the results indicate that additional serum factors are needed for optimal opsonization of yeast cells because a 35% reduction in the number of cryptococci bound to macrophages was observed with cryptococci opsonized with the reconstituted pathway compared with that observed when yeast cells were opsonized with normal serum.

Klin Monatsbl Augenheilkd, 1989 Jul, 195(1), 28 - 31
{Acute keratitis and contamination of contact lens care systems with Bacillus cereus}; van Setten GB et al.; Two patients, both contact lens wearers, were treated for acute keratitis in both eyes . Routine microbiologic tests done for all four eyes confirmed merely the presence of Staphylococcus epidermidis in the conjunctival flora; neither fungi nor any viruses were detected on the patients' corneas . However, the contact lens soaking solutions were contaminated with a large number of microorganisms, including above all--or solely--Bacillus cereus . Two of the contact lenses used were also colonized by fungi of the genus Rhodotorula, Cryptococcus albicans and Wangiella dermatidis . The acute inflammation was treated quickly and effectively in all cases by specific antimicrobial therapy . Bacterial contamination of lens care systems is well known as a potential cause of keratitis in contact lens wearers . Although the clinical importance of Bacillus cereus in ocular surface pathology is still unknown, the cases reported here indicate that this microorganism may be of pathological significance in lens care systems . The authors therefore recommend including the lens care systems in routine bacteriologic tests in all cases of corneal infection where the patient wears contact lenses.

Infect Immun, 1989 Jul, 57(7), 1946 - 52
Clearance of Cryptococcus neoformans from immunologically suppressed mice; Murphy JW; To assess the effects of cryptococcal antigen-induced immunosuppression on a Cryptococcus neoformans infection, CBA/J mice were injected intravenously with saline or suppressive doses of cryptococcal antigen (CneF) at weekly intervals and were then infected with viable C . neoformans cells . By the second week after infection, the cryptococcal antigen-injected mice had suppressed anticryptococcal delayed-type hypersensitivity (DTH) responses compared with the responses of the saline-treated, infected control mice . In addition, the immunosuppressed mice had higher numbers of cryptococcal CFU cultured from their lungs, livers, spleens, lymph nodes, and brains than did the control animals . A direct correlation of suppression of the anticryptococcal DTH response and reduced clearance of cryptococci from tissues was also observed after mice were given a single intravenous injection of CneF and infected . To determine whether or not the cryptococcal antigen was specifically reducing the clearance of C . neoformans or had a more generalized effect, mice were injected with saline or suppressive doses of CneF, infected with Listeria monocytogenes, and then followed daily for 7 days for the clearance of L . monocytogenes from spleens and on day 7 for DTH reactivity to Listeria antigen . There were no differences between the saline- and CneF-treated mice with respect to anti-Listeria DTH responses or clearance of L . monocytogenes from spleens, indicating that CneF was not altering natural resistance mechanisms responsible for early clearance of L . monocytogenes, nor was the CneF influencing the induction of the acquired immune response which was responsible for the late clearance of the bacteria . Together, these data indicate that the specific suppression of this cell-mediated immune response induced by cryptococcal antigen reduces the ability of the animals to eliminate the homologous organism (C . neoformans) but not a heterologous infectious agent, such as L . monocytogenes.

Radiol Med (Torino), 1989 Jun, 77(6), 602 - 12
{Neuro-AIDS: a multicenter neuroradiological study}; Cecchini A et al.; The results are described of a retrospective multicentric CT/MR study of 141 neuro-AIDS patients (IV group CDC classification); 114 patients were drug addicted, 13 homosexual, 8 polytransfused, and 6 had other risk factors . The mean age was 29.6 years . The pathologic agent was identified in 47 cases by c.s . fluid examination, biopsy, autopsy or specific treatment response: it was HIV in 20 cases, toxoplasmosis in 11, cryptococcosis in 9, leishmaniasis, salmonella and papovavirus in single cases . In the follow up of 2 cases, a Kaposi's sarcoma and a primitive CNS lymphoma occurred . The main clinical features were AIDS-dementia complex (45% of cases) and focal neurologic manifestations (36%) . The neuroradiological protocol consisted of 238 CT exams (97 controls), most of them with DDD (delayed double dose) technique, 7 MR exams (0.15 T) and 2 angiographies . CT findings were divided into 3 groups: negative (16%), atrophic (47%) and focal lesions (37%) . In the first and second group, HIV and cryptococcal infections were the main pathologic agents . In the third group toxoplasma infections were discovered, and TB granulomas and other pathologic conditions, with ring-like or nodular enhancement, in cortical/cortico-medullary location . In follow-up patients a high tendency of evolution towards focal lesions was observed, even in negative cases . The DDD enhancement technique allowed in most cases both the demonstration of very small lesions and their grading . According to the literature CT, though a highly sensitive method, is inferior to MR imaging; however our experience in this field is currently insufficient . The specific diagnosis of pathologic agents of neuro-AIDS is difficult, due to the high number of opportunistic AIDS-related infections and neoplasms, with overlapping features: differential diagnostic criteria can be assessed only by comparing the clinical, microbiological, topographic, CT and MR findings . CT and MR exams are necessary to guide and monitor therapy and to plan stereotaxis biopsy.

Chest, 1989 Jun, 95(6), 1180 - 4
Serious infectious complications of corticosteroid therapy for COPD; Wiest PM et al.; We report seven elderly patients with COPD who developed serious infectious complications during prolonged treatment with high doses of corticosteroids . Infections included invasive pulmonary aspergillosis, Herpes simplex stomatitis and esophagitis, cytomegalovirus pneumonia, bacterial sepsis, fungemia and meningitis due to Cryptococcus neoformans . Each of the three patients who developed invasive aspergillus pneumonia died . The efficacy of prolonged therapy with high doses of corticosteroids in patients with COPD is not proven . These cases illustrate the potential for serious infections in patients with COPD treated with corticosteroids.

Mycopathologia, 1989 Jun, 106(3), 167 - 70
Isolation of saprophytic Cryptococcus neoformans from Puerto Rico: distribution and variety; Ruiz A et al.; Until the present decade, no studies had been conducted in Puerto Rico on the saprophytic distribution and variety of Cryptococcus neoformans . Samples (522) of pigeon droppings from 14 western towns were tested for the presence of C . neoformans . The yeast was recovered from 24.7% (129 isolates) of the samples, representing 10 of the 14 towns studied . All environmental isolates were identified as C . neoformans var . neoformans using canavanine-glycine-bromthymol blue (CGB) agar . The yeast was isolated from 79.4% of the samples in one town, Isabela . The average number of yeast cells isolated from sites within this municipality was 5.1 x 10(5) per gram of pigeon droppings . This was 2.6 times the average number of yeast cells of C . neoformans isolated from sites in other towns . In addition, the yeast was isolated from four patients with the acquired immune deficiency syndrome (AIDS), each of whom died of cryptococcal meningitis . Each of these poorly encapsulated isolates was identified as C . neoformans var . neoformans using CGB agar . The results of this investigation demonstrate that C . neoformans var . neoformans is prevalent in Puerto Rico.

Mycopathologia, 1989 Jun, 106(3), 163 - 6
Virulence and antifungal susceptibility of environmental and clinical isolates of Cryptococcus neoformans from Puerto Rico; Fromtling RA et al.; Studies on the distribution, epidemiology and pathogenesis of Cryptococcus neoformans on the island of Puerto Rico are few . We have studied mouse virulence and in vitro antifungal susceptibility of 133 isolates of C . neoformans: 121 environmental and 12 clinical (9 from AIDS patients), that were isolated in Puerto Rico . In experimental CD-1 mice infected intravenously, the mean lethal dose 50% values (28 days) were greater than 5.2 x 10(6) and 1.1 x 10(5) cells/mouse for environmental and clinical isolates, respectively . Using an agar dilution assay, the minimum inhibitory concentrations of amphotericin B, ketoconazole and 5-fluorocytosine were comparable for environmental and clinical isolates in both yeast nitrogen dextrose base agar and Kimming's agar . These data suggest a difference in lethality for mice, but no difference in antifungal susceptibility of environmental and clinical isolates of C . neoformans obtained in Puerto Rico.

Infect Immun, 1989 Jun, 57(6), 1773 - 9
Characterization of a suppressor factor that regulates phagocytosis by macrophages in murine cryptococcosis; Blackstock R et al.; A T-suppressor factor which inhibits the phagocytic activity of a macrophage subset has been further characterized . This suppressor factor was first described for a murine model of cryptococcosis but was later found to be common to models of immunologic unresponsiveness . The suppressor factor was produced when suppressor cells were cultured in the presence of specific cryptococcal antigen . It could not be extracted from spleen cells and was not induced by antigen in cultures of lymph node cells . The suppressor factor was filtered through Amicon filters of 100-kilodalton (kDa) exclusion limit but was retained by filters excluding molecules of less than 50 kDa . By Sephadex G-100 chromatography, the factor eluted just ahead of bovine serum albumin (68 kDa) . The activity of the suppressor factor could not be inhibited by anticryptococcal antibody, but it was inhibited by anti-I-J alloantiserum of the same genotype as the lymphocyte which produced the factor . Absorption with an encapsulated strain of Cryptococcus neoformans removed the suppressor factor from culture supernatants, while absorption with a nonencapsulated mutant or an unrelated yeast cell had not effect . On the basis of these observations, it was apparent that the suppressor factor was idiotypic in nature and that I-J and/or the I-J-interactive molecule played a role in the function of the suppressor factor . The requirement for antigenic stimulation for the production of suppressor factor in vitro distinguished it from the T-suppressor factor 3 described by others which regulates delayed-type hypersensitivity in cryptococcosis.

Kansenshogaku Zasshi, 1989 Jun, 63(6), 649 - 53
{A case of cryptococcal meningitis successfully treated with miconazole and CSF drainage}; Fukui K et al.; Cryptococcal meningitis is the most frequent fungal infection of the central nervous system, known readily to complicate with immuno-compromised patients . There are only a few cases of primary infection in healthy non-immuno-compromised patients . Amphotericin-B (AMPH-B) and 5-Fluorocytosine (5-FC) are effective agents against Cryptococcal meningitis, although, their toxicity and drug resistance are limiting factors . However, in recent years Miconazole has been widely used against fungal infections and it's effectiveness has been reported . This is a 68 y.o . male who was admitted to Toyohashi Municipal Hospital on March 15, 1987 because of headache, vomiting, diplopia and gait disturbance . Continuous lumbar drainage was performed since lumbar puncture revealed surprisingly high cerebrospinal fluid (CSF) pressure and presence of many Cryptococcus neoformans, i.v . AMPH-B and p.o . 5-FC was also administrated . A 7 day course of i.v . AMPH-B and p.o . 5-FC showed no improvement with side effects of macrohematuria and anorexia . Then Miconazole was administrated i.v . and intrathecal (i.t.) . The clinical signs and CSF laboratory data improved after a 90 day course of Miconazole therapy and the patient was discharged on August 24 . But the patient was readmitted from March 10 to April 30, 1988, because of a slight increase of C . neoformans in CSF (17/mm3) and improved by i.v . and i.t . Miconazole . The total Miconazole dosage was 90.6 g (i.t.: 505 mg) at the first admission and 36 g (i.t.: 50 mg) at the second admission, but no side effect was seen . The reduction of elevated CSF pressure with continuous CSF drainage was also important for the treatment of such cases with increased intracranial pressure.

Boll Soc Ital Biol Sper, 1989 Jun, 65(6), 501 - 8
{Various sensitivities of yeasts to lycorine}; Garuccio I et al.; Lycorine, an Amaryllidaceae alkaloid, is a powerful inhibitor of growth in higher plants and algae . Thirty-one strains of yeasts, belonging to different genera and species, were screened to study the effect of lycorine on their growth . The strains were incubated at 25 degrees C in a 2% glucose medium with different concentrations of lycorine (10, 50 and 100 microM), and their growth after 72 hours was evaluated . Most of the strains showed no sensitivity to lycorine . However, in Schizosaccharomyces pombe (IMAT-V Pbx) and Aureobasidium pullulans (DBV A77) lycorine significantly inhibited growth (59-73%), while, on the contrary, in Saccharomycopsis fibuligera (DBV 3812) and Cryptococcus terreus (CBS 1895) it was clearly stimulated (76-140%) . The fact that lycorine inhibits growth in some yeasts while it stimulates it in others means that neither of the two previously formulated interpretations on the molecular mechanism of action of alkaloid can explain all cases . In other words, it does not seem that lycorine just inhibits protein synthesis, as claimed by Kukhanova et al . (1983), nor, on the other hand, do the data presented here prove that lycorine specifically inhibits ascorbic acid biosynthesis (Arrigoni et al., 1975) . We must now check the ability of yeasts to split lycorine and study whether yeasts do actually have an ascorbic acid system.

Hua Xi Yi Ke Da Xue Xue Bao, 1989 Jun, 20(2), 211 - 3
{Surgical treatment of primary pulmonary cryptococcal granuloma--report of 4 cases}; Zhao YF et al.; Primary pulmonary cryptococcal granuloma is not common in Sichuan . The diagnosis of this disease is difficult to make because the patient has no characteristic symptoms and the chest X-ray findings of the mass are not easily differentiated from carcinoma of the lung . The incidence of this disease is apparently increasing . Pulmonary cryptococcosis may be disseminated hematogenously to the meninges and cryptococcal meningitis is very difficult to treat . If the pulmonary lesion is localized, the patient's general condition is good with no evidence of systemic lupus erythematosis, diabetes, leukemia or lymphoma, partial resection of the lung is indicated . But, if the patient has a history of recent cryptococcal meningitis, surgery must be deferred . Four cases of primary pulmonary cryptococcal granuloma have been treated surgically supplemented with medical therapy in the First Affiliated Hospital from 1986 to 1987 . Follow-up of more than one year showed good results in each case.

Zhonghua Bing Li Xue Za Zhi, 1989 Jun, 18(2), 86 - 8
{Pathologic changes of infections in patients after receiving immunosuppressive therapy in renal allografts}; Huang SF; 30 cases of autopsies of patients who died after human renal allografts were studied . The incidence of infection was 60% and the lethal infectious complications amounted to 43% . The most common infectious agents were bacteria, including mycobacterium tuberculosis . In addition, some opportunistic agents, such as Cryptococcus, Aspergillus, mucormycosis, Pneumocystis carinii and cytomegalovirus were also found . All these patients had a history of receiving large dosage of immunosuppressive drugs such as cyclophosphamide, azathioprine, prednisone and dexamethasone after renal allografts . Pathological changes showed marked atrophy of lymphoid tissue and it was compatible with the histologic appearance of immunodeficiency . It is concluded that overuse of immunosuppressive drugs impairs the function of the immune system causing acquired immunodeficiency . Pathological features of lesions caused by the aforementioned infectious agents are also described in this paper.

Pathol Biol (Paris), 1989 Jun, 37(5 Pt 2), 690 - 3
{Value of fluconazole in the treatment of systemic yeast infection}; Bernard E et al.; 20 patients (18 men, 2 women), 10 of whom were HIV +, were given Fluconazole (F) for either systemic candidiasis (13 cases), histoplasmosis (1), or cryptococcosis (6) . The localization of the Candida infections (12 C . albicans, 1 C . tropicalis), were: septicemic (2), urinary (7), bronchial (2), esophageal (5), uveal (1), soft tissue (2), and 1 undetermined localization but a positive serology (1) . On day (d) 1, Candidiasis patients were given an initial dose of 400 mg (for septicemia) or 200 mg (other localizations) of FIV or PO, then 200 or 100 mg per d . The length of treatment lasted from 28 to 70 d . Evolution was favorable in all the patients . 4 relapses occurred after the end of treatment: at 10 d, a septicemic candidiasis (C . tropicalis) in 1 patient who had prosthetic endocarditis; and at 1 month, digestive candidiasis in 3 HIV + patients . For the patient, infected by Histoplasma capsulatum, despite a clinical improvement, urine were still positive at day 75 . The patients with cryptococcosis (5 meningitidis in the AIDS patients) and renal (1) (kidney transplant) were given on the average 400 mg a d, IV or PO (mean length 8 weeks) . Only 5 patients were evaluable . For 2 of the meningitis patients with other localizations, standard treatment was instituted due to the persistence of positive cultures . For the 2 other patients, the cerebrospinal fluid (1) and the urine (1) were sterilized by the 3d week . But they relapsed 1 month after the treatment stopped . For the 18 patients evaluable, clinical and biological tolerance was good except for 1 patient with transaminases rise for which fluconazole was probably the cause.

Klin Wochenschr, 1989 Jun 1, 67(11), 598 - 604
{Cryptococcus neoformans meningoencephalitis and multiple infections in AIDS}; Zoller WG et al.; A 40-year old homosexual AIDS patient recovering from a Pneumocystis carinii pneumonia developed a Cryptococcus neoformans infection with involvement of the central nervous system (CNS) which could be treated successfully with amphotericin B and flucytosine . After a symptom-free interval of 4 1/2 months, a new acute fatal disease of the CNS did not reveal a cryptococcosis relapse but a necrotizing Toxoplasma encephalitis, a cytomegalovirus infection and striking cultural findings of Staphylococcus aureus in all organs examined . Neither by culture nor by histology Cr . neoformans could be detected in the CNS or in the other organs examined . The temporal course of the Cr . neoformans infection and its specific diagnosis are commented . It is demonstrated that (during or after successful therapy of Pneumocystis carinii pneumonia) a specific cultural examination of specimens from the respiratory tract for Cr . neoformans is needed, in order to recognize a Cr . neoformans infection in its primary stage, i.e . before hematogenous dissemination of Cr . neoformans leading to the secondary stage of the infection.

AIDS, 1989 Jun, 3(6), 389 - 90
Isolation of Cryptococcus neoformans from houses of AIDS-associated cryptococcosis patients in Bujumbura (Burundi); Swinne D et al.; Cryptococcus neoformans var . neoformans, which is responsible for AIDS-associated cryptococcosis in Bujumbura, was isolated in the domestic environment of seven out of 20 patients with AIDS-associated cryptococcosis . The findings prove that in his own domestic environment, the HIV-positive patient in central Africa is frequently exposed to the yeast and these observations lead us to insist on the suitability of carrying out a systematic survey by means of soluble antigens-sensitized latex in every HIV-positive patient . This also proves the importance of a follow-up of the 'cured' patients who easily can be recontaminated after their return homePIP: Soil, pigeon droppings, and dust were collected from 20 houses in Bujumbura which were inhabited by AIDS-associated cryptococcosis patients . Cryptocococcus neoformans variant neoformans was isolated from samples in 7 of the houses . This finding suggests that all HIV-positive patients should be tested for cryptococcal antigen and that patients cured of cryptococcosis may be reinfected on their return home .

Am J Ophthalmol, 1989 May 15, 107(5), 523 - 7
Optic neuropathy associated with cryptococcal arachnoiditis in AIDS patients; Lipson BK et al.; We studied two cases of bilateral visual loss secondary to an optic neuropathy in patients with cryptococcal meningitis . In both cases a history of visual loss after the onset of an episode of cryptococcal meningitis was elicited . Visual fields were consistent with optic nerve disease . The patients' visual loss appeared to be the result of perineuritic adhesive arachnoiditis . Although no surgical interventions were carried out in our patients, medical or surgical intervention may be useful to prevent or relieve constrictive arachnoiditis and preserve vision in selected patients.

Jpn J Med, 1989 May-Jun, 28(3), 399 - 401
Sjögren's syndrome following gastrectomy and chemotherapy for gastric malignant lymphoma; Monno S et al.; The case of a 72-year-old man who developed Sjogren's syndrome three years following gastrectomy and chemotherapy for gastric malignant lymphoma is reported . The patient eventually died of systemic cryptococcal infection, and autopsy revealed no recurrence of the malignant lymphoma . Review of the literature indicates lymphoproliferative disease preceding the development of Sjogren's syndrome is extremely rare.

Br J Ophthalmol, 1989 May, 73(5), 397 - 8
Amphotericin B induced ocular toxicity in cryptococcal meningitis; Li PK et al.; We report a case of acute visual loss after a test dose (1 mg) of intravenous amphotericin B administered to a patient with systemic lupus erythematosus and with cryptococcal meningitis . Her visual acuity was normal prior to the injection of amphotericin B . The meningitis subsequently responded to miconazole and flucytosine treatment . Our findings suggest that amphotericin B should be withheld in the treatment of cryptococcal meningitis if disease of the optic nerve is strongly suspected.

Am J Med, 1989 May, 86(5), 528 - 32
Cerebral infarctions and transient neurologic deficits associated with acquired immunodeficiency syndrome; Engstrom JW et al.; PURPOSE: Little information is available concerning the clinical importance of cerebral infarction in patients with acquired immunodeficiency syndrome (AIDS) . The purpose of this retrospective study was two-fold: (1) to determine the frequency and clinical characteristics of cerebral infarction and transient neurologic deficits (TNDs) among patients with AIDS; and (2) to identify specific patient subgroups at risk for such complications and whether there were underlying associated diseases requiring specific therapy . PATIENTS AND METHODS: Neurology inpatient and consult service records, neuropathology reports, and the University of California, San Francisco, AIDS computerized registry were used in identifying study cases . Information on demographic background, associated clinical diagnoses, presenting neurologic symptoms and signs, laboratory results, pathologic findings, and clinical follow-up was obtained from each patient's medical record . RESULTS: Twenty-five patients with AIDS (mean age, 38) having clinical or pathologic findings suggestive of focal cerebral ischemia or infarction were identified . Ten patients had non-hemorrhagic cerebral infarctions, 13 had acute TNDs, and two had both . Cerebral infarction was associated with central nervous system (CNS) infections (cryptococcus, four; tuberculosis, one; zoster vasculitis, one) and cardiogenic embolism (one) . TNDs were associated with toxoplasmosis (four), cerebral infarction (two), cryptococcal meningitis (one), vasculitis (one), and CNS Kaposi's sarcoma (one) . A presumptive cause was absent in five cases of cerebral infarction and eight of TND . All five patients with pathologically proven macroscopic cerebral infarcts were diagnosed clinically before death . CONCLUSIONS: We conclude the following: (1) AIDS patients, especially given their young age, appear to be increased risk for cerebral infarction and TND . (2) Cerebral infarction and TND may be the initial presentation of AIDS . (3) TND and cerebral infarction often signify treatable CNS infection among AIDS patients . (4) The causes of AIDS-related cerebral infarction and TND are unknown in many cases.

Mycopathologia, 1989 May, 106(2), 113 - 9
Tissue changes in cryptococcosis: histologic alteration from gelatinous to suppurative granulomatous tissue response with asteroid body; Narisawa Y et al.; The histologic variety and transformation in cutaneous cryptococcosis with acute lymphocytic leukemia before antifungal treatment and after the start of treatment were studied by the light and electron microscopic examinations . The initial cutaneous lesions before treatment revealed gelatinous tissue reactions, and Cryptococcus neoformans (serotype A) were isolated from the skin biopsy specimen and blood . However, later recurrent cutaneous lesions receiving antifungal treatment revealed suppurative granulomatous tissue reactions, and fungal cultures of the skin biopsy specimen changed to negative even though numerous yeasts stained with PAS were observed in skin lesions . Moreover, in the later lesion a few giant cells contained asteroid bodies without central spores . Ultrastructure of the later cutaneous lesions is presented.

Mycoses, 1989 May, 32(5), 250 - 2
Cryptococcus neoformans var . neoformans and munia birds; Pal M; Cr . neoformans var . neoformans has been persistently demonstrated in the saprobic environment of caged munia birds at a local zoological garden . The pathogen was also cultured from the beaks, feathers and legs of these birds . It is suggested that the role of munia birds should be further investigated to understand the ecology of this important human pathogen.

J Infect, 1989 May, 18(3), 289 - 92
Cryptococcosis complicating continuous ambulatory peritoneal dialysis; Kaczmarski EB et al.; We report a case of invasive cryptococcosis complicating continuous ambulatory peritoneal dialysis and its successful treatment . This form of infection has not been previously described.

Br J Dermatol, 1989 May, 120(5), 683 - 7
Cutaneous cryptococcosis: treatment with oral fluconazole; Shuttleworth D et al.; A case of cutaneous cryptococcosis is described in an immunocompromised patient . The initial lesion developed on the dorsum of the hand following trauma and was initially thought to be neoplastic . Satellite subcutaneous lesions developed in a 'sporotrichoid' pattern along the forearm . Treatment with oral fluconazole resulted in the complete resolution of the lesions . This is the first published report of the use of fluconazole in the treatment of cutaneous cryptococcosis.

J R Soc Med, 1989 May, 82(5), 278 - 80
AIDS: neurological opportunist infections in central London; Guiloff RJ; Twenty six (41%) of 64 central London cases of AIDS with nervous system involvement during the course of the illness had neurological opportunist infection . Cytomegalovirus and Toxoplasma gondii were the commonest agents in 22 cases with central nervous system (CNS) infection . Eight cases had herpes zoster radiculopathy . Other infections included those caused by Cryptococcus neoformans, Mycobacterium tuberculosis and papova JC virus . Prognosis was generally poor, irrespective of whether the opportunist infection was treatable.

Eur J Clin Microbiol Infect Dis, 1989 May, 8(5), 457 - 65
Current concepts in cryptococcosis; Patterson TF et al.; Cryptococcus neoformans has become an increasingly important pathogen . Cryptococcosis is an important cause of morbidity and mortality in immunocompromised hosts and is the second most common fungal infection complicating AIDS . In recent years, research has focused on the host defenses against Cryptococcus and has led to an improved understanding of the capsular virulence of the organism, the mechanisms of T-cell defenses, and the role of phagocytic cells in the fungistasis and killing of cryptocci . Amphotericin B with or without flucytosine has clearly improved treatment of cryptococcosis, but therapy is associated with significant toxicity . Current investigation is focused on the triazoles, which may offer improved therapy for cryptococcosis . In this report, we review recent developments in the understanding of the host defenses against Cryptococcocus and discuss current recommendations for the management of cryptococcosis.

J Immunol, 1989 May 1, 142(9), 3219 - 24
Fungicidal activity of IFN-gamma-activated macrophages . Extracellular killing of Cryptococcus neoformans; Flesch IE et al.; Cryptococcus neoformans is an encapsulated yeast-form fungus which causes pulmonary and meningeal infections preferentially in the immunocompromised host . It is thought that cell-mediated immunity is important for acquired resistance against cryptococcosis with activated macrophages as the final effector cells . However, specific polysaccharides in the capsule of C . neoformans protect the fungus from adherence to phagocytes and from subsequent phagocytosis . We have studied extracellular killing of C . neoformans by IFN-gamma-activated macrophages and their products . Murine bone marrow-derived macrophages stimulated with rIFN-gamma for 24 h were able to effectively suppress the growth of C . neoformans and the effect of IFN-gamma was augmented by LPS . Killing of C . neoformans was also achieved by cell-free supernatants from bone marrow-derived macrophages stimulated with IFN-gamma plus LPS . Our results indicate that killing of C . neoformans by activated macrophages is independent from toxic oxygen radicals and mediated by secreted protein(s) of apparent molecular mass of 15 and 30 kDa . These findings indicate that activated macrophages play a major role in host defense, although the fungus resists phagocytosis and remains in the extracellular milieu.

Ann Ig, 1989 May-Aug, 1(3-4), 827 - 40
{In vitro study of the antifungal activity of two chlorine derivatives to be used in antisepsis}; Bianchi P et al.; The activity of two chlorine derivates, sodium hypochlorite in water solution with NaCl (product A) and electrolytic chloroxidant (product B) has been tested in vitro against potentially human pathogenic fungi (Aspergillus niger, Aspergillus fumigatus, Microsporum gypseum, Candida albicans, Cryptococcus neoformans, Trichophyton mentagrophytes, Microsporum canis, Epidermophyton floccosum, Trichophyton rubrum, Sporotrix schenkii) . For A . niger, the relation of the two compounds has also been considered between mycelial and sporidial forms . Dilutions used ranged from 0.15 to 10% (corresponding to 17.2-1150 ppm of active principle for product A, and to 18.3-1220 ppm of active principle for product B) . These were applied for different times in order to assess the minimal inhibitory concentration (M.I.C.) and to evaluate the survival time of the microorganisms tested, which were strains from the collection of the Institute of Mycology, (Faculty of Agrarian Science, Perugia) and recently isolated ones from animal and vegetable tissues, cultivated on Sabouraud medium . The cell suspension to be tested was obtained on nutrient broth in shaken flasks (120 rpm) at 28 degrees C for 48 h, and was separated by centrifugation and 10000 rpm at 5 degrees C for 20 min, repeatedly washed with sterile physiologic saline and resuspended in sterile water where it was submitted to delicate pressure in order to fragment the mycelium . Activity tests were carried out on Sabouraud broth and Sabouraud agar with controls for every case without the active principle . Aliquots of the suspensions (microrganism++ + disinfectant) were transferred at regular intervals (1, 3, 5 and 10 minutes) to the two substrates in liquid and solid state, and the growth of microorganisms was followed at 28 degrees C for 48-72 h in the case of yeasts, and for up to 21 days in the case of sower growing fungi . The cell content of the different suspensions was found to range from 10(4) to 10(9) UFC/ml . The active chlorine contents of the two compounds was evaluated by iodometry simultaneously with the pH of the different solutions . Useful data were obtained from the comparison of the two systems of activity assessment of the fluid and agarized substrate . It was thus found that the two compounds were equally active against the species tested . Some of these (A . fumigatus, M . gypseum, A . niger, C . albicans, C . neoformans) were less sensitive to the compounds examined (doses for cell inactivation 0.62-2.5% for product A, and O.15-1.25% for product B) where at any rate product B was more active.(ABSTRACT TRUNCATED AT 400 WORDS)

Exp Parasitol, 1989 May, 68(4), 450 - 61
Pneumocystis carinii: sequence from ribosomal RNA implies a close relationship with fungi; Stringer SL et al.; Pneumocystis carinii is the etiologic agent of a lethal pneumonia which occurs in patients with the acquired immune deficiency syndrome (AIDS) and other immunocompromised hosts . The basic biochemical and genetic characteristics of P . carinii are poorly understood and its taxonomic classification as a protozoan is uncertain . To address the taxonomic question, a method was developed for the extraction of total RNA from P . carinii . Denaturing agarose gel electrophoresis showed the two ribosomal RNA species of P . carinii to be similar in size to those of other lower eukaryotes, including Saccharomyces cerevisiae . Three portions of the small ribosomal RNA of P . carinii were sequenced by reverse transcription from oligonucleotide primers . Three hundred seventy-two nucleotides of sequence were obtained . The sequence derived from P . carinii RNA contained regions that previous phylogenetic studies have shown to be highly variable among species, as well as regions that are highly conserved . Comparison of the P . carinii sequence to corresponding sequences of organisms from other taxa showed the P . carinii sequence to be more similar to sequences from the fungi (Saccharomyces cerevisiae, Neurospora crassa, Candida albicans, and Cryptococcus diffuens) than to protozoan sequences . These data suggest that P . carinii is more closely related to fungi than to protozoa.

Am J Ophthalmol, 1989 Apr 15, 107(4), 373 - 80
The spectrum of optic nerve disease in human immunodeficiency virus infection; Winward KE et al.; We studied four patients with HIV-associated optic neuropathies . One had syphilitic optic perineuritis, which responded promptly and completely to penicillin therapy . The second had cytomegalovirus papillitis and visual acuity subsequently deteriorated to no light perception . The third showed varicella zoster optic neuritis, which improved after intravenous acyclovir treatment . The fourth patient developed cryptococcal retrobulbar neuritis and died shortly thereafter . Optic neuropathy was among the initial symptoms of HIV infection in two of the four cases.

Dermatol Clin, 1989 Apr, 7(2), 269 - 74
Cutaneous cryptococcosis; Hernandez AD; Cutaneous cryptococcosis occurs in 10 to 15% of patients with cryptococcosis . Because the cutaneous crytpococcosis may precede clinical signs of central nervous system disease, early recognition may lead to more successful outcomes . This article reviews the mycology, epidemiology, pathology, clinical manifestations, and treatment of this disease, focusing primarily on the cutaneous aspects.

Mycoses, 1989 Apr, 32(4), 171 - 80
Cryptococcus neoformans in the seminal fluid of an AIDS patient . A contribution to the clinical course of cryptococcosis; Staib F et al.; In a 33-year-old HIV-positive homosexual male suffering from unexplained headache, cryptococcosis was diagnosed in a progressive secondary stage . After treatment with the standard combination therapy of amphotericin B + flucytosine for 34 d, the patient was clinically symptom-free and discharged, upon his own request, from the hospital . He remained under ambulatory mycological control . After an interval of 65 d during which the urine had been free from Cryptococcus neoformans (Cr.n.), the fungus could not be isolated from urine but 3 X 10(5) CFUs/ml were found in the seminal fluid . Andrologically, teratospermia and hyposemia were present . There were no clinical signs in the genitourinary tract including the prostate . The significance of ecological niches for Cr.n . colonization of the genitourinary tract after antimycotic therapy is discussed . In such cases, in addition to cultural examination of urine for Cr.n . by the membrane filtration technique (MFT) and Staib agar, an additional cultural examination of seminal fluid is recommended . It is also proposed to pay more attention to Cr.n . in andrological examinations . Special regard should be given to a possible occurrence of Cr.n . in the seminal fluid of AIDS patients . In cytology of the seminal fluid, use of the Giemsa stain is unsuitable for the purpose of Cr.n . detection . For this reason, it should be supplemented by PAS staining.

Mycopathologia, 1989 Apr, 106(1), 31 - 4
Itraconazole vs amphotericin B: in vitro comparative evaluation of the minimal inhibitory concentration (MIC) against clinically isolated yeasts; Lombardi G et al.; Itraconazole is a triazole compound which, following several clinical trials, has begun to be used for therapy of mycotic infections . This new drug, with a broad-spectrum antifungal activity, can be orally administered . The Authors studied the in vitro susceptibility to amphotericin B and itraconazole of the following clinical isolates of pathogenic yeasts: 100 Candida albicans, 20 C . tropicalis, 20 C . parapsilosis, 8 C . guilliermondii, 6 C . pseudotropicalis, 24 Torulopsis glabrata and 16 Cryptococcus neoformans . Serial two-fold dilution, from 100 micrograms/ml to 0.04 micrograms/ml, of each drug were prepared in Yeast Nitrogen Base + Glucose 5%, after dissolving the itraconazole in dimethylsulfoxide (DMSO) and amphotericin B in 5% glucose solution . Amphotericin B (MIC90: 3.12 micrograms/ml) was found to have an average in vitro MIC six-fold lower than itraconazole (MIC90: 25 micrograms/ml) . Thus, even though itraconazole is active, amphotericin B remains one of the most effective of the antifungal drugs.

Antimicrob Agents Chemother, 1989 Apr, 33(4), 467 - 9
Pharmacokinetics and tissue penetration of fluconazole in rabbits; Walsh TJ et al.; Fluconazole is a new bis-triazole antifungal compound which has in vivo and in vitro activity against Candida spp . and Cryptococcus neoformans and excellent penetration into cerebrospinal fluid . However, little is known about the penetration of fluconazole into tissue sites other than cerebrospinal fluid . We therefore studied by high-pressure liquid chromatography the penetration of fluconazole into nine different tissue sites at times of peak and trough concentrations in plasma in rabbits . Fluconazole penetrated into all tissue sites . Tissue/plasma concentration ratios were greater at time of trough concentrations in plasma than at times of peak concentrations in plasma . The finding that fluconazole penetrated into target organs commonly infected by Candida spp . and C . neoformans further supports the therapeutic potential of fluconazole for disseminated candidiasis or cryptococcosis in immunocompromised hosts.

Infect Immun, 1989 Apr, 57(4), 1158 - 64
Effects of cyclosporin A on the cells responsible for the anticryptococcal cell-mediated immune response and its regulation; Fidel PL Jr et al.; Cyclosporin A (CsA), a potent immunosuppressive drug, was used to explore further the induction, expression, and regulation of lymphoid cells involved in the delayed-type hypersensitivity (DTH) response to cryptococcal antigen(s) . We found that the induction of the cells responsible for DTH (TDH cells) was not affected by CsA, but their expression was inhibited in CsA-treated mice . The inhibition of expression of the TDH cells could not be attributed to the Cryptococcus neoformans-specific suppressor T (Ts) cells, even though the Ts cells were induced in CsA-treated mice . Instead, the suppressed expression of the TDH cells in CsA-treated mice was a direct effect of CsA or its products . Our studies with CsA also resulted in the first identification of a population of cells that significantly amplify the anticryptococcal DTH response . The amplifier cells were induced in mice that were given a primary immunizing dose of cryptococcal antigen in complete Freund adjuvant, and they amplified the anticryptococcal DTH response in recipient mice when they were transferred at the time of immunization of the recipient . The amplifier cell population was distinct from the TDH cells in that CsA inhibited the production of the amplifying cells but did not affect the induction of TDH cells . Amplification of the DTH response was a cell-mediated event, since cells but not serum from immunized mice mediated the amplified response in recipient mice . Thus, CsA enabled us to characterize anticryptococcal TDH and Ts cells further and to add to the immune cell circuit of the cryptococcal system a distinct population of cells that amplifies the anticryptococcal DTH response.

Eur J Clin Microbiol Infect Dis, 1989 Apr, 8(4), 362 - 75
Serological techniques for diagnosis of fungal infection; de Repentigny L; This review summarizes recent developments in the serodiagnosis of candidiasis, aspergillosis, cryptococcosis, histoplasmosis, blastomycosis, coccidioidomycosis, mucormycosis and sporotrichosis . A number of studies have substantiated the presence of circulating antigens in invasive candidiasis, invasive aspergillosis, disseminated histoplasmosis and coccidioidomycosis, and immunoassays for antigen detection provide moderate sensitivity but high specificity for disease . Improved detection may result mainly from repeated serum or concentrated urine samplings rather than from the development of more sensitive immunoassays . Immunoblot analysis of the serological response is a useful tool for the identification of immunogenic fungal components that elicit a specific antibody response in invasive disease . This method, and others, have been successfully applied to the study of the immune response to several fungi, including Candida, Aspergillus and Rhizopus.

Oral Surg Oral Med Oral Pathol, 1989 Mar, 67(3), 322 - 6
Immune deficiency with polymorphic reticulosis; Najjar T et al.; A case of fatal polymorphic reticulosis, currently considered to be a peripheral T cell lymphoma, that was initially seen as a nasolabial swelling with a left lower lobe pulmonary nodule in a 40-year-old woman is reported . At autopsy, it was found to be associated with disseminated cryptococcosis and Pneumocystis carinii pneumonia associated with secondary severe immunodeficiency of unknown originPublication Types:

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