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