Cryptococci

J Med Vet Mycol, 1992, 30(4), 293 - 300
Granulocyte-colony stimulating factor facilitates the restoration of resistance to opportunistic fungi in leukopenic mice; Uchida K et al.; Administration of recombinant human granulocyte-colony stimulating factor (G-CSF), which induces hemopoietic precursor cells to proliferate and differentiate into neutrophils, protected leukopenic mice infected with opportunistic fungi . Mice were injected with cyclophosphamide and were then subcutaneously (s.c.) or intravenously (i.v.) administered 15-120 micrograms G-CSF kg-1 day-1 for 3 days . The number of peripheral blood neutrophils in the G-CSF treated mice was significantly increased 48 h after G-CSF administration . All leukopenic mice infected with either Candida albicans, Cryptococcus neoformans or Aspergillus fumigatus were significantly protected by treatment with the G-CSF . Moreover, G-CSF treatment caused a decrease in the number of viable yeasts in kidneys of Candida infected mice . These data suggest that prophylactic therapy with G-CSF may be useful against fungal infections in an immunocompromised host.

Dtsch Med Wochenschr, 1991 Dec 20, 116(51-52), 1955 - 8
{Cryptococcal meningitis in AIDS: successful long-term prophylaxis with fluconazole}; Gluck T et al.; A 30-year-old, HIV-positive, man who had been repeatedly treated with amphotericin B for oral thrush, developed headaches, fever up to 38.5 degrees C, dizzy spells with falling tendency, as well as disorder of speech and word finding . Cerebrospinal fluid (CSF) contained 5700/3 cells, of which 90% were encapsulated yeast-fungus . Cryptococcal antigen titres were elevated both in serum (1:256) and CSF (1:1024), providing the diagnosis of cryptococcal meningitis . Intravenous treatment was started with amphotericin B, 0.3 mg/kg daily and flucytosine, 150 mg/kg daily . The clinical, microbiological and serological findings regressed after 4 weeks . After 8 weeks the creatinine concentration rose to 2.5 mg/dl . Because amphotericin B nephrotoxicity was suspected, further intravenous administration was stopped after a cumulative dosage of 2 g . He was placed on a prophylactic dosage of fluconazole, 100 mg by mouth twice daily . The cryptococcal antigen titre had fallen to normal within one year . The prophylactic regimen has been continued now for three years without recurrence or other fungal infection.

Recenti Prog Med, 1991 Dec, 82(12), 652 - 60
{Mycoses and adrenocortical function . New pathogenetic aspects of adrenal hypofunction}; Angeli A et al.; Three aspects of the possible relationships between adrenocortical function and mycoses are considered: a) abnormal steroid hormone concentrations that may favour onset and/or clinical course of mycotic diseases; b) presence of granulomas in the adrenal glands during systemic mycoses; c) effects of antifungal drugs on steroidogenesis . Glucocorticoids are potent inhibitors of T-lymphocyte proliferation, in that they affect both the production of IL-1 from monocytes/macrophages and IL-2 from activated T-lymphocytes . Consequently opportunistic fungal infections are frequently observed in patients with chronic hypercortisolism (Cushing's syndrome) and in particular in those under chronic treatment with corticoids . On the other hand, mucocutaneous candidiasis is a prominent feature of the autoimmune polyglandular syndrome type I, characterized by adrenal insufficiency, hypoparathyroidism and mucocutaneous candidiasis . Its onset is usually at childhood, first with symptoms and signs of the fungal infection and then with those of endocrine failure . It is a complex disorder, familiar or sporadic, not linked to particular HLA haplotype, potentially associated with other autoimmune diseases (endocrine and not), thus forming the so called candidiasis endocrinopathy syndrome (CES) . Adrenal involvement is very frequent in systemic mycoses, such as histoplasmosis (Histoplasma capsulatum), cryptococcosis (Cryptococcus neoformans), and paracoccidioidomycosis . From the pathogenetic view point, corticostatins-defensins may play a role . They are a family of recently discovered cationic peptides, that are able to inhibit adrenal steroidogenesis by interfering with ACTH at the specific receptor level . The pharmacological effects of ketoconazole on adrenal (and gonadal) steroidogenesis are a focus of great interest . This compound has been demonstrated to be a potent inhibitor of cytochrome P450-dependent enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)

Bol Asoc Med P R, 1991 Dec, 83(12), 548 - 51
CNS involvement in AIDS patients as seen with CT and MR: a review; Rodriguez WL et al.; The human immunodeficiency virus infected persons frequently have manifestations of central nervous system disfunction . These can be primary involvement or secondary processes such as infections or tumors . The present paper presents a short review of radiologic CNS findings in patients with AIDS as seen on CT and or MRI . The radiologic findings of HIV-1 encephalitis, toxoplasmosis, primary CNS lymphoma, PMLE, cryptococcosis, histoplasmosis, CMV encephalitis, HVS and varicella are presented . We expect this will ultimately help in the management of the AIDS patient.

J Clin Microbiol, 1991 Dec, 29(12), 2873 - 6
Evaluation of a new method for identification of Cryptococcus neoformans which uses serologic tests aided by selected biological tests; Kabasawa K et al.; A new method for identifying Cryptococcus neoformans isolates and their serotypes by the slide agglutination test using five kinds of factor sera, with the aid of nitrate reduction, phenol oxidase, and growth at 37 degrees C tests was evaluated by using 36 reference strains and 75 clinical isolates of C . neoformans . The results showed that the reference strains were identified exactly as they were labeled, and clinical isolates were identified as C . neoformans serotypes A, D, and AD . C . neoformans could be distinguished from other Cryptococcus species that cross-reacted with factor sera by their ability to grow at 37 degrees C . These results indicate that the slide agglutination test combined the use of factor sera for isolates which grow at 37 degrees C is a useful method for identification of C . neoformans and their serotypes and that the nitrate reduction test (negative in 100% of the isolates) and the phenol oxidase test (positive in approximately 95% of the isolates) can be used to confirm that the species is C . neoformans.

ANNA J, 1991 Dec, 18(6), 585 - 6, 596
Medication review: fluconazole; Holechek MJ; Fluconazole is an antifungal agent available for the treatment of oropharyngeal and esophageal candida and cryptococcal meningitis . It has been found to be equal to or more efficacious than amphotericin B in treating oral and esophageal candidiasis and in providing maintenance therapy for cryptococcal meningitis . It still remains to be seen if it can be equally effective in treating acute cryptococcal infections and systemic candidiasis . In these fungal infections, amphotericin B remains the clinically proven drug of choice . To its advantage, it does not cause acute renal failure, bone marrow depression, or suppress corticosteroid production which are significant drawbacks to other available agents . It is a drug with great promise for its specific indications, but more studies in renal failure and organ transplant patients are needed to firmly establish its efficacy in these populations.

Arch Intern Med, 1991 Dec, 151(12), 2458 - 64
Thrush can be prevented in patients with acquired immunodeficiency syndrome and the acquired immunodeficiency syndrome-related complex . Randomized, double-blind, placebo-controlled study of 100-mg oral fluconazole daily; Stevens DA et al.; Recurrent oropharyngeal candidiasis is common in patients with acquired immunodeficiency syndrome and the acquired immunodeficiency syndrome-related complex . It causes local pain and discomfort, loss of taste, and aversion to food and may lead to secondary complications . We examined, in a double-blind study, whether recurrent thrush could be prevented by prophylaxis . Twenty-five patients with one to four previous thrush episodes who had no thrush at the outset of the study were randomized to receive 100 mg of fluconazole or placebo daily for 12 weeks . If thrush occurred, prophylaxis was stopped and patients were treated conventionally, after which prophylaxis was resumed . After the randomized study, some patients were given continuous fluconazole (open phase) . In the randomized study, thrush occurred in eight of 13 placebo-treated patients and none of 12 fluconazole-treated patients . Possible side effects were not different between the groups . Dermatophytosis and onychomycosis and cryptococcuria also improved in the fluconazole-treated patients, and fungal colonization was significantly decreased . One episode of thrush occurred in the open phase in an intermittently compliant patient (group total, 71.5 patient-months of fluconazole treatment); in contrast, the 25 patients also had had two episodes of Candida esophagitis, three of cryptococcosis, and 13 of dermatophytosis before entry . Subsequent to entry in the randomized trial, in 92.3 patient-months without fluconazole, there were 35 episodes of thrush, one of esophagitis, one of cryptococcemia, and one of dermatophytosis, and preexisting dermatophytosis and onychomycosis were unchanged or worsened . Individual patients observed with and without fluconazole treatment also showed its efficacy . In conclusion, thrush can be prevented in patients with acquired immunodeficiency syndrome and the acquired immunodeficiency syndrome-related complex with negligible toxic effects . Larger trials to confirm prevention of all mycoses with prophylaxis should be considered.

J Formos Med Assoc, 1991 Dec, 90(12), 1218 - 21
Cryptococcal infection presenting with lumbosacral polyradiculopathy: report of a case; Wan CL et al.; Cryptococcal infection presenting primarily as lumbosacral polyradiculopathy is rare . We report on a 57-year-old man with lumbosacral polyradiculopathy, and in which a culture from the cerebrospinal fluid grew Cryptococcus neoformans . A serum cryptococcal antigen study showed a positive reaction . Biopsy specimens from the spinal nerve rootlet showed evidence of arachnoiditis and direct involvement of the nerve root by Cryptococcus neoformans . It is important to remember that localized lumbosacral polyradiculopathy can be the sole initial manifestation of cryptococcosis.

Med Klin (Munich), 1991 Dec, 86 Suppl 1, 8 - 10
{The treatment of aspergillosis, cryptococcosis and histoplasmosis in immunocompromised patients . Report of experience in the United States}; Hostetler JS et al.; Itraconazole has emerged as an important new oral agent in the treatment of systemic fungal infections . We report a summary of available data on its use in aspergillosis, cryptococcosis and histoplasmosis compiled in the United States with particular attention to the immunocompromised host . Data has been accrued in open-label studies including 57 patients with cryptococcal disease where the overall response rate among patients with meningitis was 86%, 28 patients (seven with HIV infection) with invasive aspergillus where the overall response rates were 80% in non-AIDS and 42% in HIV patients . Data is summarized on six patients with allergic bronchopulmonary aspergillosis, all of whom improved on therapy, and twelve patients with histoplasmosis including eight with AIDS, eleven of whom responded (three newly reported cases are included) . In summary, itraconazole showed activity in human studies of aspergillosis, cryptococcosis and histoplasmosis with minimal toxicity . Itraconazole offers a new oral alternative to conventional amphotericin B therapy in these infections . Comparative studies are needed to clarify its role.

Med Klin (Munich), 1991 Dec, 86 Suppl 1, 5 - 8
{In-vitro and in-vivo activity of itraconazole}; Van Cutsem J; Itraconazole is a lipophilic triazole with potent in vitro activity . It is also highly efficacious after topical, oral and parenteral administration . The antifungal activity of itraconazole has been evaluated against more than 6500 different strains, belonging to more than 260 fungal species using the serial decimal dilution test in fluid media (BHI broth) . Candida, Torulopsis, Cryptococcus, Pityrosporum (Dixon broth), various other yeasts, dermatophytes, Aspergillus, Penicillium, Sporothrix, dimorphic fungi (MP and YP), Phaeohyphomycetes, Entomophthorales and various Hyalohyphomycetes are sensitive . Most strains of Fusarium and Zygomycetes are poorly sensitive . Itraconazole was administered orally and parenterally in normal and in immunocompromised guinea-pigs, infected with C . albicans, Cr . neoformans, H . duboisii, Sp . schenckii, P . marneffei and A . fumigatus . It was efficacious both in survival of the animals and in eliminating the fungi from the various tissues . Itraconazole was superior to fluconazole in candidosis, cryptococcosis, sporotrichosis and aspergillosis, to amphotericin B and to flucytosine in candidosis, cryptococcosis and aspergillosis . No comparative studies were done up to now for the other deep mycoses . The results of combination therapy of itraconazole with fluconazole in cryptococcosis were indifferent, with 5-flucytosine or amphotericin B, additive or synergistic in systemic candidosis, cryptococcosis and aspergillosis . No drug-related side-effects were observed after oral or parenteral administration of itraconazole.

Med Klin (Munich), 1991 Dec, 86 Suppl 1, 19 - 22
{Mycoses as opportunistic infections in AIDS patients}; Viviani MA; 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 nine of twelve patients and with itraconazole plus flucytosine in eight of ten patients . Of the 31 patients who received itraconazole maintenance therapy for up to 27 months, four (13%) had relapses; 14 (45%) did not have relapses, and decline of serum antigen was detected in twelve 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.

Med Klin (Munich), 1991 Dec, 86 Suppl 1, 11 - 3
{Therapy of systemic mycoses in neutropenic patients using itraconazole . A comparative, randomized study with amphotericin B}; van't Wout JW et al.; Systemic mycosis constitute a serious threat for the patient with granulocytopenia . The most important causative agents are Candida spp., Aspergillus spp . and, to a lesser extent, Cryptococcus neoformans, Mucoraceae and Pseudoallescheria boydii . Treatment of such infections with amphotericin B is difficult, because of the many side-effects of this medicine, such as hypotension, fever, shivering, thrombophlebitis, nephrotoxicity, renal tubular acidosis, hypokalaemia, anaemia and thrombocytopenia . In addition, the efficacy of amphotericin B in the treatment of proven mycotic infections in granulocytopenic patients is not very great . Itraconazole is a new, oral antifungal agent which is active in vitro and in animal experiments against both Candida and Aspergillus . In patients without granulocytopenia, itraconazole appeared to be effective in the treatment of deep Candida and Aspergillus infections . On the basis of the above data, a randomized comparative investigation was carried out unto the efficacy of amphotericin B and itraconazole in the treatment of systemic mycoses in neutropenic patients.

Arch Pathol Lab Med, 1991 Nov, 115(11), 1145 - 9
Combined Fontana-Masson-mucin staining of Cryptococcus neoformans; Lazcano O et al.; Cryptococci react positively with various histochemical stains, including the Fontana-Masson (FM), which stains the cell wall, and mucin stains, such as alcian blue and mucicarmine, which stain the capsule . Combinations of the FM stain with both the alcian blue and mucicarmine stains were performed on paraffin-embedded tissue specimens that were obtained from 15 patients who had culture-proved cryptococcosis . Combined FM-mucicarmine and FM-alcian blue stains were compared with other individual fungal stains . The FM stain, followed by either the mucicarmine or alcian blue stain, distinctively demonstrated both the cell wall and capsule of most organisms . More organisms were recognized in the combined stains than with either stain done individually . No interference between the stains was noted . Combining the FM stain with either of these two mucin stains appears to be helpful for identifying cryptococci.

Tidsskr Nor Laegeforen, 1991 Nov 10, 111(27), 3288 - 90
{Pulmonary pseudotumor caused by Cryptococcus neoformans}; Luhr H et al.; Since 1923, eight cases of cryptococcosis have been described in Norway, all with meningeal affection . A distinct, solitary infiltration in the upper lobe of the right lung was discovered in a 68 year-old woman . The lobe was extirpated . Microbiological and histological investigations showed infection with Cryptococcus neoformans . No antimycotic treatment was given . Four months later the patient developed osteomyelitis of the skull due to cryptococcosis, and was treated successfully with amphotericin B and flucytosin . Further investigation of the patient revealed a defect in the T-lymphocyte immune system, but it is uncertain whether this was of any significance for the development of the cryptococcus infection.

Med Clin (Barc), 1991 Nov 9, 97(16), 604 - 8
{Cryptococcosis of the central nervous system . Clinical and diagnostic characteristics}; Jimenez-Mejias ME et al.; BACKGROUND: Evaluation of the clinical features and diagnostic methods in the cryptococcosis of central nervous system (CNS), so as to facilitate a rapid recognition which may result in earlier diagnosis in view of the rapid increase in frequency shown in that condition . METHODS: A retrospective study of 13 patients with CNS cryptococcosis seen during the last 4 years . The isolation of C . neoformans in CSF, cerebral biopsy or other appropriate tissue was required for inclusion . The following were evaluated: 1) Age, sex, and underlying disease; 2) Clinical features; 3) Yield of biochemical, microbiological, pathological and imaging diagnostic procedures; 4) Treatment and evolution . RESULTS: Age (X +/- SD): 37 +/- 20 years (range: 15-81) . Sex: 77% males . Underlying disease was identified in 10 cases (77%): HIV infection in 7 (54%), diabetes mellitus in 2, alcohol abuse in 2, systemic erythematous lupus on corticoid and immunosuppressant therapy in 1 and chronic liver disease in 1 . Clinical features on admission: abnormal behaviour in 10 (77%), headache in 10, low/high grade fever in 9 (69%), abnormal consciousness in 7, respiratory features in 5 (38%); motor deficit, cranial nerve involvement and visual abnormalities in 4 (31%) each; and meningeal signs in 3 . Investigation of CSF was carried out in 12 cases . The biochemical studies were normal in 5 (42%) . China ink stain was positive in 55% of cases, and latex agglutination in 80% . CSF culture was diagnostic in 92% of cases and the culture for C . neoformans was positive in 2 cerebral and one pulmonary biopsies and in two urine cultures . All patients were treated with amphotericin B and flucytosine was associated in 9 . Two patients were subsequently treated with fluconazole . The outcome was good in 8 patients, and 4 had sequelae . One case relapsed . CONCLUSIONS: 1) HIV infection is the most common underlying disease . 2) There is a high rate of CNS cryptococcosis with normal CSF or with mild biochemical abnormalities . 3) The yield of the microbiological studies of CSF is high, with diagnostic confirmation in 92% of cases . 4) Differences in CNS cryptococcosis were not found between cases with HIV infection and those with other underlying diseases.

South Med J, 1991 Nov, 84(11), 1407 - 8
Significance of cryptococcal antigen titers in patients with AIDS; Shahab ST et al.; We have described a patient with AIDS and cryptococcal antigen titers of 1:262,144 in CSF and 1:268,435,456 in serum . Although the prognosis is poor in AIDS patients with high cryptococcal antigen titers, this patient responded well to treatment and has been free of clinical recurrence of cryptococcal infection for 2 years.

Infect Immun, 1991 Nov, 59(11), 3883 - 8
Encapsulation of Cryptococcus neoformans impairs antigen-specific T-cell responses; Collins HL et al.; The encapsulated yeast Cryptococcus neoformans is a significant cause of opportunistic infection in patients with impaired cell-mediated immunity . The major virulence determinant of the organism is an antiphagocytic polysaccharide capsule synthesized after entry into the host . Using both an encapsulated virulent strain and an acapsular avirulent mutant, we have demonstrated the reduced ability of the encapsulated strain to stimulate specific T-cell responses in vitro . This reduction was mediated by the antiphagocytic action of the capsule rather than by direct inhibition of antigen processing and presentation, since prior opsonization with complement enhanced the ingestion of encapsulated yeast cells by purified antigen-presenting cells and allowed significant T-cell activation . Once ingestion had occurred, cryptococci were efficiently processed by activated macrophages via a chloroquine-sensitive pathway . Cryptococcal antigens were available for T-cell recognition within 1 to 2 h of interaction with macrophages and presented in a major histocompatibility complex-restricted manner . Our results suggest that the antiphagocytic action of the polysaccharide capsule is an important determinant for the development of T-cell immunity to C . neoformans.

Rev Inst Med Trop Sao Paulo, 1991 Nov-Dec, 33(6), 485 - 90
{Detection of capsular polysaccharide antigen of Cryptococcus neoformans in patients with AIDS and neurocryptococcosis in São Paulo, Brazil}; Calvo B et al.; Capsular polysaccharide antigen (AgPC) of Cryptococcus neoformans was detected by latex agglutination technique (LA) in cerebrospinal fluid and serum of patients with AIDS during their first central nervous system manifestation of the disease . Direct mycological examination and culture were used as controls . Sensitivity was 100% by LA allowing an early specific treatment of cryptococcosis . Initial titres of AgPC in such patients can be > 1000000 and it appears that when such titres are present in the serum they are related to mortality during treatment . Surviving patients showed positivity of the direct mycological examination and AgPC of C . neoformans in cerebrospinal fluid and sera even after treatment and clinical recovery.

J Protozool, 1991 Nov-Dec, 38(6), 95S - 96S
Cryptococcus neoformans can be misidentified as a microsporidian: studies of lung lesions in leprosy patients; Furuta M et al.; Pulmonary lesions seen in autopsies of leprosy patients were initially thought to involve microsporidial infection . After immunohistochemical studies, it was concluded that the infectious microorganism was Cryptococcus neoformans.

J Protozool, 1991 Nov-Dec, 38(6), 191S - 194S
Detection of human Pneumocystis carinii by the polymerase chain reaction; Becker-Hapak M et al.; Oligonucleotide primers were prepared from a clone (B12) which has been shown to be a repetitive sequence in the rat P . carinii genome . Polymerase chain reaction was employed to amplify both rat and human P . carinii DNA . The detection limit of the assay was approximately 600 ng of total nucleic acid . Amplification products from both the rat and human isolates (ca . 780 bp) were characterized by denaturing gradient gel electrophoresis after digestion with Sau3A . No amplification products were obtained when DNA from the following potential pulmonary pathogens were used in identical reactions: Aspergillus fumigatus, Cryptococcus neoformans, Candida albicans, Mycobacterium avium-intracellulare and cytomegalovirus . In a blind study using the B12 primers, P . carinii DNA was successfully amplified in clinical samples which were positive by direct immunofluorescence assay (IFA) as well as in some specimens not identified by direct IFA.

Antimicrob Agents Chemother, 1991 Nov, 35(11), 2185 - 90
In vitro and in vivo antifungal activities of BMY-28864, a water-soluble pradimicin derivative; Kakushima M et al.; BMY-28864, a water-soluble pradimicin derivative, had potent in vitro activity against a wide variety of fungi, including those associated with deep-seated mycosis; it inhibited the growth of standard strains and clinical isolates at concentrations of 12.5 micrograms/ml or less . At the MIC or higher concentrations, BMY-28864 was fungicidal for Candida albicans under both growing and nongrowing conditions . BMY-28864 expressed fungicidal activity only in the presence of Ca2+, and its activity was totally diminished when ethylene glycol-bis(2-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), a Ca2+ chelator, was added to the test medium . The effectiveness of intravenously administered BMY-28864 in vivo was examined and compared with that of amphotericin B in mouse models of fungal infections . Both normal and cyclophosphamide-treated immunosuppressed mice infected with C . albicans, Cryptococcus neoformans, or Aspergillus fumigatus responded to therapy with BMY-28864 (50% protective doses of 17, 18, and 37 mg/kg of body weight in normal mice and of 32, 35, and 51 mg/kg in cyclophosphamide-treated mice, respectively) . Lethal lung infections were also established with C . albicans or A . fumigatus in cyclophosphamide-treated mice . The 50% protective doses of BMY-28864 were 15 and 23 mg/kg per dose against C . albicans and A . fumigatus, respectively . The immunosuppression induced by intraperitoneal administration of 200 mg of cyclophosphamide per kg lasted for 5 days, and total recovery was observed by day 7.

Mod Pathol, 1991 Nov, 4(6), 707 - 11
Gastrointestinal cryptococcosis; Washington K et al.; Cryptococcal infection of the gastrointestinal (GI) tract is rarely reported, either in disseminated disease or as an isolated finding . We report a case of gastric cryptococcal infection diagnosed by endoscopic biopsy as the initial presentation of the acquired immunodeficiency syndrome (AIDS), and an additional seven cases found by reviewing 23 other autopsy cases of disseminated or pulmonary cryptococcal infection . The patient with gastric cryptococcosis was a 38-year-old man who presented with symptoms of gastroesophageal reflux including odynophagia . Upper GI endoscopy showed Candida esophagitis and gastric nodules . Biopsy of the nodules revealed cryptococcal infection and granulomatous inflammation of the fundic mucosa and submucosa . The patient died 3 weeks later despite anti-fungal therapy . Autopsy revealed widespread cryptococcal infection involving the cecum but not the stomach, suggesting that the gastric lesions resolved with therapy . The sites of infection in the seven other cases were esophagus (three), stomach (one), terminal ileum (one), colon (three), gallbladder (one), and in a focus of Kaposi's sarcoma in the wall of the small bowel (one) . Esophageal candidiasis was also present in two of the cases of esophageal cryptococcal infection . Predisposing factors were AIDS (3), hematologic malignancy (3), and corticosteroid therapy (1) . In summary, we report a case of gastric cryptococcosis and conclude that cryptococcal infection involves the GI tract more commonly than has been previously reported, with 8/24 (33%) cases positive in our autopsy series . Of clinical significance is the observation that GI cryptococcal infection may be the initial presentation of disseminated disease in the immunocompromised patient, and cryptococcal infection of the esophagus may be found in the setting of esophageal candidiasis.

Can J Microbiol, 1991 Nov, 37(11), 834 - 9
Susceptibility of congenitally immunodeficient mice to a nonencapsulated strain of Cryptococcus neoformans; Salkowski CA et al.; The susceptibility of congenitally immunodeficient mice to a nonencapsulated strain of Cryptococcus neoformans (strain M7) was evaluated . Gnotobiotic mice with defined congenital defects in innate immunity (beige) or cell-mediated immunity (athymic) or with combined defects in innate and cellular immunity (beige athymic) were i.v . challenged with C . neoformans M7 . The nonencapsulated strain of C . neoformans produced a persistent low-grade infection in the brains of all immunodeficient and immunocompetent mice used in this study . Immunocompetent mice (nu/+;bg/+) and immunodeficient bg/bg mice readily cleared nonencapsulated cryptococci from their kidneys, liver, lungs, and spleen . In contrast to nu/+ mice, nu/nu mice had a reduced capacity to clear nonencapsulated cryptococci from their kidneys and liver after i.v . challenge . Both bg/bg-nu/nu and bg/bg-nu/+ mice developed a low-grade infection in their kidneys, liver, lungs, and spleen, which was maintained throughout the 21-day study . Persistent infections were not due to reversion to an encapsulated state . These data indicate that a capsule may not always be necessary for C . neoformans to survive, in vivo, in tissues of immunodeficient and immunocompetent mice.

Rev Infect Dis, 1991 Nov-Dec, 13(6), 1163 - 9
The ecology of Cryptococcus neoformans and the epidemiology of cryptococcosis; Levitz SM; The ecology of Cryptococcus neoformans and the epidemiology of cryptococcosis are reviewed . Two varieties of C . neoformans have been recognized . C . neoformans variety neoformans has been found in nature worldwide, primarily in association with bird droppings, although nonavian sources have also been found . Most cases of human cryptococcosis are caused by this variety . C . neoformans var . gattii has recently been isolated in nature in association with Eucalyptus trees . Infections caused by this variety occur mainly in tropical and subtropical regions . Because exposure to C . neoformans is probably common and clinically apparent cases of cryptococcosis in healthy hosts are rare, it is presumed that most people can mount adequate host defenses upon exposure to the organism . At least 5%-10% of patients with AIDS become infected with Cryptococcus; the epidemiology of this infection is different in many respects from that seen in patients without AIDS.

J Clin Microbiol, 1991 Nov, 29(11), 2363 - 7
Diagnosis of invasive candidiasis by detection of mannan antigen by using the avidin-biotin enzyme immunoassay; Nakamura A et al.; The diagnosis of invasive candidiasis was attempted by detection of circulating mannan antigen by using an avidin-biotin-amplified enzyme-linked immunosorbent assay (AB-ELISA), and this method was compared with the conventional culture method . Mannan antigen was detected by AB-ELISA in the sera of 16 (84.2%) of the 19 patients with invasive candidiasis . On the other hand, for 34 immunocompromised candidiasis-free patients, including 8 with aspergillosis or cryptococcosis, mannan antigen was positive during only 1 of the 67 febrile episodes and in the serum of none of the 50 outpatients without infections . The results were also negative for all patients with deep-seated mycoses other than candidiasis . However, the mannan level was low (less than 2.0 ng/ml) in the serum of 63.2% of the patients with invasive candidiasis . The positivity rate of blood cultures was 31.6%, and that of blood cultures and/or cultures of samples from sterile sites combined was 47.4% . The advantages of the diagnosis based on antigen detection by AB-ELISA are considered to be a higher sensitivity and elimination of nonspecific reactions by the introduction of the avidin-biotin system and pretreatment of sera by heating . In addition, it is considered essential for high sensitivity that transient mannan antigenemia be determined frequently so that it is not overlooked . In light of its sensitivity and specificity, this method is considered to be clinically useful in the diagnosis of invasive candidiasis.

Nihon Kyobu Shikkan Gakkai Zasshi, 1991 Nov, 29(11), 1457 - 63
{A case of severe summer-type hypersensitivity pneumonitis treated with high-dose administration of steroid}; Arai M et al.; A 40-year-old man who lived in a wooden house built 30 years ago presented with complaints of fever, dry cough and dyspnea . Chest X-ray findings showed interstitial shadows throughout bilateral lung fields . After admission, high-dose administration of 3000 mg of methylprednisolone was performed because of deterioration of chest X-ray shadows and symptoms . In a week, clinical data and symptoms improved . Findings of BAL fluid on admission revealed a relative increase of lymphocytes, neutrophils and mast cells, and pathological findings of transbronchial lung biopsy revealed non-caseous granulation and alveolitis . Precipitating antibodies and indirect fluorescent antibodies against Trichosporon cutaneum and Cryptococcus neoformans had positive reactions and T . cutaneum was isolated and identified from the patient's house . A diagnosis of summer-type hypersensitivity pneumonitis was made according to the criteria advocated by Ando et al . This seemed to be a rare case of summer-type hypersensitivity pneumonitis prolonged after isolation from his normal living environment, successfully treated by high-dose administration of steroid.

J Antibiot (Tokyo), 1991 Nov, 44(11), 1228 - 36
Antifungal and antiviral activities of benanomicins and their analogues; Kondo S et al.; In vitro activities of benanomicins and their analogues against human immunodeficiency virus and fungi including Candida, Cryptococcus and Aspergillus, were examined . The free carboxyl group and at least one sugar moiety in the benanomicins were essential for their activities . Benanomicin A was most active and had low toxicity, and was selected as the best candidate for chemotherapy.

Neurol Clin, 1991 Nov, 9(4), 867 - 88
Central nervous system infections in cancer patients; Pruitt AA; In the immunocompromised patient, even mild forms of any combination of headache, meningismus, altered mental status, or focal neurologic signs should initiate an evaluation for possible CNS infection . The limited signs and symptoms of acute CNS infection are not due to specific organisms but to pathologic changes at the neuroanatomic site of infection . The initial clinical history, examination, laboratory, and neuroradiographic data will narrow the problem to one of several groups of agents, although it may not be possible to specify a single causative agent . It should be remembered that several concurrent infections (i.e., CMV and toxoplasmosis, aspergillosis, and bacterial sepsis) may be present . Thus, the clinician should rely on broad antibiotic coverage appropriate to the suspected causative agent or agents at the site of infection . It may be necessary to offer broad-spectrum antibiotic coverage for a CSF presentation that is subsequently found to result from a viral illness or from a noninfectious cause . However, one should avoid undertreating those infections for which specific therapy can be offered, and broad-spectrum treatment usually will not be regretted . Uncertainty in diagnosis following noninvasive procedures should lead to a brain biopsy . Although many of the infections discussed in this article have a poor prognosis, some of the most common pathogens, such as Cryptococcus, Listeria, and Toxoplasma, have effective specific therapies to which the patient should have access as rapidly as possible . The clinician who has successfully treated a patient with CNS infection should remain vigilant for late sequelae or recurrence of infection . Chronic treatment of some infections, such as toxoplasmosis or aspergillosis, may be necessary . The reintroduction of steroids for the treatment of an underlying cancer may reactivate previously treated disease, such as cryptococcosis, and periodic CSF surveillance is appropriate under these circumstances . Recurrence of the symptoms should raise the suspicion of recurrent or new infection, and the patient also should be evaluated with CT or MRI for the development of hydrocephalus or for new metastatic disease . In patients who have had varicella-zoster infection, postherpetic neuralgia and delayed arteritis may develop . Seizures, hearing loss, and neuropsychologic sequelae may follow any meningoencephalitis . The patient should always be reevaluated for the possibility of infection with a different opportunistic organism . CNS infections remain a major cause of morbidity and mortality in immunosuppressed patients with malignancies . In one series, 60% of such patients died as a result of their CNS infection, many at a time when the underlying disease had an otherwise good prognosis.(ABSTRACT TRUNCATED AT 400 WORDS)

Arch Pathol Lab Med, 1991 Nov, 115(11), 1125 - 32
Bone marrow examination for the diagnosis of mycobacterial and fungal infections in the acquired immunodeficiency syndrome; Nichols L et al.; In a series of 342 bone marrow examinations from 314 patients with human immunodeficiency virus infection, 70 examinations (20%) detected opportunistic mycobacterial or fungal infections . One hundred eleven of the 314 patients had such infections, and, hence, 63% (70/111) were detected by bone marrow examination . Special stains for microorganisms detected 16 (32%) of 50 Mycobacterium avium complex infections, 10 (22%) of 45 Mycobacterium tuberculosis infections, eight (73%) of 11 Histoplasma capsulatum infections, and five (83%) of six Cryptococcus neoformans infections . Bone marrow cultures detected 36 (72%) of the 50 M avium complex infections, 13 (29%) of the 45 M tuberculosis infections, and 63% of the fungal infections . Marrow examination revealed infection in only one of the 70 specimens (1%) collected to evaluate thrombocytopenia alone or hematologic malignancy, but in 69 (25%) of 274 with fever, neutropenia, anemia, or miscellaneous other indications for marrow examination . Granulomas were detected in 102 (30%) of the biopsy specimens, including 71 (64%) of those in cases with mycobacterial or fungal infection . The granulomas showed caseous necrosis in nine cases, all in patients with tuberculosis, and the 27 cases with tuberculosis-associated granulomas tended to show large, tightly cohesive granulomas . The presence of granulomas correlated with opportunistic infection in 82 (80%) of 102 cases . Without granulomas, special stains were positive in only eight (3%) of 240 specimens . These results suggest that (1) bone marrow granulomas are a common and valuable histologic clue to opportunistic infection; (2) without them, special stains may not be a cost-efficient way to diagnose such infection; and (3) bone marrow examination can be a useful method of diagnosing opportunistic mycobacterial and fungal infections in patients with fever, anemia or neutropenia, and underlying human immunodeficiency virus infection.

Arch Pathol Lab Med, 1991 Nov, 115(11), 1112 - 24
The neuropathology of human immunodeficiency virus infection . The Dallas, Texas, experience; Burns DK et al.; Postmortem neuropathologic changes were evaluated in 141 consecutive patients dying with human immunodeficiency virus infection at publicly supported hospitals affiliated with the University of Texas Southwestern Medical Center in Dallas, between August 1984 and September 1990 . Morphologic abnormalities were identified in 112 cases (79%) . Cytomegalovirus was the most common opportunistic infection encountered, with characteristic viral inclusions identified in 23 patients, and presumptive evidence of infection in six additional patients . Progressive multifocal leukoencephalopathy was present in four patients . Gram-positive bacterial infections were identified in six patients, and mycobacterial infections in three patients . Opportunistic fungal infections included cryptococcosis (13 cases), histoplasmosis (two cases), and coccidioidomycosis (one case) . Toxoplasmosis was uncommon, with active or quiescent lesions identified in five patients . Lymphoma was present in nine patients and was primary in the central nervous system in five patients . Multinucleate giant cell (human immunodeficiency virus) encephalitis was identified in 28 patients . In an additional 26 patients, microglial nodules and/or more generalized white-matter abnormalities were encountered in the absence of multinucleate giant cells, cytomegalovirus inclusions, or systemic cytomegalovirus infection . Vacuolar change was present in 21% of spinal cords, and was highly correlated with cytomegalovirus infection in the nervous system . Mixed infections and/or neoplasms were identified in 24 patients . This survey documents a high frequency of neuropathologic abnormalities in human immunodeficiency virus-infected individuals in a geographical region of the United States not represented in previous series . Variations noted in the frequencies of specific central nervous system disorders between this and other study populations reinforce the need for continuing documentation of geographical trends in human immunodeficiency virus-associated disorders.

Surg Neurol, 1991 Nov, 36(5), 394 - 9
Abdominal cyst formation following ventriculoperitoneal shunt in a case of hydrocephalus due to cryptococcal meningitis . Case report: completely cured by surgical removal of the cyst and treatment with a newly developed anti-fungal drug (Difulcan); Izumoto S et al.; A 54-year-old woman was admitted to the hospital for evaluation of meningitis . Tuberculous meningitis was suspected initially because of general findings and a high adenosine deaminase activity (ADA) value in the cerebrospinal fluid . Administration of antituberculous drugs was not effective . Computed tomography scanning revealed progression of ventricular enlargement . A ventriculo-peritoneal shunt was placed upon diagnosis of hydrocephalus due to meningitis . The presence of a large abdominal cyst formation was demonstrated . Cryptococcus was detected in the cyst fluid, leading to a diagnosis of cryptococcal meningitis . Intravenous administration of fluconazole (400 mg/day) was begun . Excision of the cyst was performed when Cryptococcus was no longer detected in the cyst fluid . The patient recovered uneventfully.

Am J Clin Pathol, 1991 Nov, 96(5), 577 - 81
Fungi in megakaryocytes . An unusual manifestation of fungal infection of the bone marrow; Ferry JA et al.; When fungi infect the bone marrow, typically they are associated with granuloma formation and/or necrosis, and the fungi are found within histiocytes or admixed with necrotic debris . Recently two bone marrow biopsy specimens were encountered in which fungi were confined to the cytoplasm of megakaryocytes, a finding not previously reported in the literature . The first case was that of a 46-year-old man with pulmonary histoplasmosis and no known immunodeficiency . The second was that of a 38-year-old man with the acquired immune deficiency syndrome and cryptococcal meningitis . In the first case, many megakaryocytes contained fungal forms consistent with Histoplasma . In the second, one small cluster of megakaryocytes contained several budding yeast consistent with Cryptococcus . Neither marrow biopsy specimen had necrosis, granulomas, or histiocytic infiltration . In both cases, because of the unusual localization of the fungi, they were initially overlooked . The bone marrow may contain fungi even in the absence of abnormalities suggesting fungal infection on routinely stained sections . A silver stain or a periodic acid--Schiff stain should be performed on all marrow biopsy specimens in cases of known or suspected fungal infection outside the marrow . The phenomenon of megakaryocyte emperipolesis is well known, and this process may be responsible for the apparent ability of megakaryocytes to internalize fungi.

Rev Infect Dis, 1991 Nov-Dec, 13(6), 1126 - 30
Endophthalmitis in a patient with disseminated cryptococcosis and AIDS who was treated with itraconazole; Denning DW et al.; We report a case of presumed cryptococcal endophthalmitis that occurred in a patient with severe disseminated cryptococcosis and AIDS . Multiple small, spherical lesions appeared bilaterally on the surface of the retina 2 weeks after cryptococcal meningitis was diagnosed; the lesions were associated with multiple blind spots, blurred vision, and the perception of flaring of light . Over the next week, many more lesions with adjacent hemorrhages appeared . Therapy with itraconazole over the next 3 months resulted in complete resolution of the lesions . Cryptococcal endophthalmitis is a rare disease . Fewer than 20 cases, including five in patients with AIDS, have previously been reported . None of these patients regained normal vision.

J Clin Microbiol, 1991 Oct, 29(10), 2296 - 9
Evaluation of the MicroScan Rapid Yeast Identification panel; St Germain G et al.; The MicroScan Rapid Yeast Identification (RYI) panel is a 4-h microdilution system for identification of clinical yeastlike isolates . Its accuracy was evaluated by using 357 isolates encompassing 11 genera and 30 species . The RYI panel identifications were compared with those obtained by the API 20C system assisted with morphological characterization on cornmeal-Tween 80 agar . The panels were read both visually and with the AutoScan-4, a computer-controlled microplate reader . Both the RYI panel and the API 20C system correctly identified 78% of the strains within 4 and 72 h, respectively, with no additional tests . Supplementary tests recommended by the manufacturers made it possible to identify up to 96.6% (AutoScan-4) and 98.9% (API 20C) of the strains . The accuracy of the RYI panel was 99.5% with common strains and 92.1% with less common strains . The RYI panel misidentified 10 or 12 strains and failed to identify 2 or 3 strains, depending on whether it was read with the AutoScan-4 or visually . Errors occurred with one strain of Torulopsis glabrata and the less common yeasts T . candida, Candida lusitaniae, C . lambica, C . rugosa, C . stellatoidea, Cryptococcus albidus, C . laurentii, and C . uniguttulatus . Overall, the RYI panel appears to be a reliable system for identification of the more common clinical yeast isolates.

Infect Immun, 1991 Oct, 59(10), 3393 - 7
Activation of human peripheral blood mononuclear cells by interleukin-2 and granulocyte-macrophage colony-stimulating factor to inhibit Cryptococcus neoformans; Levitz SM; The abilities of selected cytokines to activate human peripheral blood mononuclear cells (PBMC) to inhibit and kill the opportunistic fungus Cryptococcus neoformans were studied . PBMC were cultured for 7 days in cell wells containing no cytokines, tumor necrosis factor (TNF), gamma interferon (IFN-gamma), 1,25-dihydroxycholecalciferol (vitamin D3), granulocyte-macrophage colony-stimulating factor (GM-CSF), or interleukin-2 (IL-2) and were then challenged for 24 h with a fixed number of CFU of C . neoformans . The number of CFU increased in wells containing no cytokines, TNF, IFN-gamma, or vitamin D3 and remained about the same in wells containing GM-CSF . In contrast, the number of CFU in wells containing IL-2-stimulated PBMC decreased, suggesting fungicidal activity . Optimal conditions for IL-2 stimulation included a minimum of 5 days of incubation of PBMC with IL-2, a concentration of 100 U of IL-2 per ml, and a high ratio of effectors to fungi . Separation of IL-2-stimulated PBMC based upon their adherence to plastic revealed that antifungal activity resided in the nonadherent fraction . These data demonstrate that IL-2 and GM-CSF are capable of stimulating PBMC-mediated antifungal activity and suggest that these cytokines may play physiological or pharmacological roles in host defenses against cryptococcosis.

Q J Med, 1991 Oct, 81(294), 857 - 70
Neurological manifestations of systemic lupus erythematosus: a prospective study; Wong KL et al.; A prospective study of the neurological manifestations in all patients with systemic lupus erythematous (SLE) was conducted between February 1985 to January 1989 . Excluding herpes zoster infection of peripheral or cranial nerves, post-herpetic neuralgia and migraine, 36 neurological episodes occurred in 33 patients . The presenting symptoms were mental confusion (10), psychosis (five), seizures (six), focal neurological deficit (three), coma (two), headache (five), blurring of vision (three), neuropathy (one) and myelopathy (one) . Of these manifestations, only eight episodes were due to primary involvement by SLE: psychosis (two), seizure (two), multiple cerebral infarcts (one), papillitis (one), neuropathy (one) and myelopathy (one) . Infection was the most common secondary cause of neurological episodes: all 10 episodes of mental confusion (fungal seven, pyogenic two, tuberculous one, nocardial one); two of six seizures (tuberculous one, pyogenic one); all five headaches (tuberculous meningitis three, cryptococcal meningitis two) . The other secondary causes included steroid psychosis (two), hypertensive encephalopathy with seizure (one) and hypertensive retinopathy (one) . Three of five cases of focal neurological deficit were due to macrovascular disease rather than to vasculitic infarction . We concluded that cerebral psychosis was a relatively rare presentation in our patients with SLE . In patients who presented with a neurological problem, especially mental confusion, efforts should be made to ascertain the underlying cause, especially if this may be an infection.

J Med Assoc Thai, 1991 Oct, 74(10), 454 - 8
Latex agglutination test for diagnosing cryptococcosis; Imwidthaya P et al.; Fourteen cases of systemic cryptococcosis were admitted to Siriraj Hospital during 1987 to 1989 . These included 5 male and 9 female patients aged 4-65 years . The most significant manifestation was cryptococcal meningitis and systemic lupus erythematosus was the most common underlying disease . Culture test for C . neoformans was negative after 28 days of treatment and the latex agglutination test decreased to 1+ agglutination within 49 days of treatment . The latex agglutination test may also be positive in other bacterial, fungal, connective tissue and malignant diseases . A definite diagnosis must, therefore, rely on conventional methods (finding organisms in specimens, culture for the organism) . The latex agglutination test is valuable for monitoring patients (decreasing titer indicates a good response) . The disease recurred in 4 cases . In cases of cryptococcal meningitis, lumbar puncture should periodically be performed to obtain cerebrospinal fluid for mycological study . In addition the patients should be observed for symptoms and signs.

Neurologia, 1991 Oct, 6(8), 295 - 8
{Meningitis caused by Candida albicans in a male patient infected by HIV and failure of treatment with amphotericin B}; Salavert M et al.; We report a case of Candida albicans meningitis in a male with human immunodeficiency virus (HIV) infection . This finding has seldom been reported, both in this group of patients and in those with other causes of immunosuppression or other underlying diseases . We discuss the clinical presentation and the features of cerebrospinal fluid, which showed only a mild inflammatory reaction as found in other fungal meningitis (basically cryptococcal) in AIDS patients . Finally, we emphasize the ineffectiveness of amphotericin therapy to achieve a complete microbiological cure and to prevent the relapse of meningitis in this patient . We also stress the need to make an early diagnosis in cases of fungal meningitis in patients with VIH infection, so that appropriate therapy is begun as soon as possible.

J Antimicrob Chemother, 1991 Oct, 28 Suppl B, 63 - 71
Treatment of murine candidosis and cryptococcosis with a unilamellar liposomal amphotericin B formulation (AmBisome); Adler-Moore JP et al.; This investigation examined the therapeutic efficacy of AmBisome, a unilamellar (55-75 nm) liposome amphotericin B preparation with a murine LD50 by the intravenous route of greater than 175 mg/kg amphotericin B . Both fungal burden and survival were used to evaluate the drug's efficacy against murine candidosis and cryptococcosis . Single and multiple dose intravenous treatment with AmBisome (2.5, 5.0 and 10.0 mg/kg) reduced the colony forming units/mg kidney in candida-infected mice by 99% and improved survival by at least 40% relative to untreated control mice . Repeated intravenous dosing of candida-infected mice with equivalent amounts (0.75 mg/kg) of conventional amphotericin B (Fungizone) or AmBisome showed comparable reduction of yeasts in the kidneys . When mice were infected systemically with Cryptococcus neoformans, all but one of the 30 mice given AmBisome (5.0, 7.5 or 10.0 mg/kg) survived until the experiment was terminated 35 days after infection . Liver and spleen cultures from AmBisome-treated mice were negative for fungal growth . All the mice given conventional amphotericin B intraperitoneally at 4.5 mg/kg survived and cleared the infection from the livers although some of the mice had infected spleens . The percentage of cultured brains free of cryptococcus was 89% following treatment with 10.0 mg/kg AmBisome, and 80% with 4.5 mg/kg conventional drug . These preclinical studies of systemic candidosis and cryptococcosis demonstrate comparable efficacy of AmBisome and conventional amphotericin B at low doses and improved efficacy with AmBisome at doses higher than can be safely administered of the conventional drug.

J Antimicrob Chemother, 1991 Oct, 28 Suppl B, 27 - 38
Amphotericin B: an introduction; Warnock DW; Amphotericin B has a broad spectrum of action that includes most of the major fungal pathogens of man . This drug binds to the membrane sterols of fungal cells, causing impairment of their barrier function and loss of cell constituents . Metabolic disruption and cell death are consequent upon membrane alterations . Investigations of the sterol content of mutant strains of Candida albicans and Cryptococcus neoformans has demonstrated that resistance is often associated with alterations in membrane sterol composition . Treatment failure due to the development of amphotericin B resistance is an uncommon problem . It has tended to occur in patients receiving treatment with cytotoxic drugs . Interactions between amphotericin B and a number of other antimicrobial drugs have been observed in tests in vitro and in vivo . However, apart from one report that the combination with flucytosine is superior to amphotericin B on its own in the treatment of cryptococcal meningitis, there have been no controlled trials to support the use of drug combinations in human infections.

J Antimicrob Chemother, 1991 Oct, 28 Suppl B, 105 - 9
Experience with liposomal amphotericin B (AmBisome) in cryptococcal meningitis in AIDS; Coker RJ et al.; Three patients with AIDS who had cryptococcal meningitis were treated with liposomal amphotericin B after unsuccessful treatment with fluconazole and conventional amphotericin B . One patient responded but relapsed nine weeks later; he responded to a second course of treatment but again relapsed and subsequently died . Another patient deteriorated despite an improvement in cryptococcal antigen titres . The third patient was found to have culture negative CSF and treatment was therefore stopped . None of the patients suffered any adverse effects and renal function improved in all after conventional amphotericin was stopped and liposomal amphotericin B commenced.

J Antimicrob Chemother, 1991 Oct, 28 Suppl B, 1 - 16
Epidemiology and pathogenesis of systemic fungal infections in the immunocompromised host; Denning DW; The epidemiology and pathogenesis of invasive candidosis and aspergillosis, cryptococcal meningitis, mucormycosis and disseminated histoplasmosis are reviewed . Particular areas of growth of knowledge that are emphasized are the epidemiology of candidosis and aspergillosis, putative virulence factors in aspergillosis and the pathogenesis of cryptococcosis.

Vet Q, 1991 Oct, 13(4), 185 - 90
Gastric granulomatous cryptococcosis mimicking gastric carcinoma in a dog; van der Gaag I et al.; An ulcerated lesion resembling a tumour in the lesser curvature of the stomach of a 3-year-old male Dobermann pinscher was found to be caused by Cryptococcus neoformans . The dog had been vomiting for two months and had slight leucocytosis and anaemia . Biopsies of the ulcerated lesion revealed granulomatous inflammation and many cryptococci, which were particularly prominent in PAS and mucicarmine stained sections . No other lesions were found at necropsy.

Infect Immun, 1991 Oct, 59(10), 3700 - 7
Cryptococcus neoformans serotype A glucuronoxylomannan-protein conjugate vaccines: synthesis, characterization, and immunogenicity; Devi SJ et al.; We synthesized Cryptococcus neoformans serotype A glucuronoxylomannan (GXM) conjugate vaccines under conditions suitable for human use to prevent disseminated cryptococcosis . The purified, sonicated GXM was derivatized with adipic acid dihydrazide through either hydroxyl or carboxyl groups and then covalently bound to tetanus toxoid (TT) or Pseudomonas aeruginosa exoprotein A (rEPA) . The immunogenicity of these conjugates was evaluated in BALB/c and general purpose mice by subcutaneous injection in saline . The conjugates elicited higher GXM antibody responses than GXM alone . Booster immunoglobulin G (IgG) and IgM responses were elicited by all conjugates in BALB/c mice . The conjugates prepared through hydroxyl activation (GXM-TT2 and GXM-rEPA) were more immunogenic than the one prepared through carboxyl activation (GXM-TT1) . GXM antibody response was enhanced by the administration of monophosphoryl lipid A 2 days following the injection of GXM-TT2 (P less than 0.03) . The conjugates also elicited IgG antibodies to the carrier proteins . Gel diffusion tests using conjugate-induced hyperimmune sera and chemically modified GXMs suggested that the specificity of GXM-TT1-induced antibodies was conferred by the O-acetyl groups . Hyperimmune sera generated by GXM-TT2 precipitated with the chemically unmodified and the de-O-acetylated GXMs but not with the carboxyl-reduced and de-O-acetylated GXM . GXM-TT2-induced hyperimmune serum also precipitated with the capsular polysaccharides of C . neoformans serotypes D, B, and C . The conjugate vaccines prepared through hydroxyl activation of the GXM are sufficiently immunogenic and appear to be suitable for clinical evaluation.

Toxicol Appl Pharmacol, 1991 Sep 15, 110(3), 403 - 15
Modulation of human alveolar macrophage properties by ozone exposure in vitro; Becker S et al.; We have investigated changes in human alveolar macrophage (HAM) function after exposure in vitro to ozone (O3) (0.1-1.0 ppm for 2-4 hr) . The functions studied reflect concern that O3 is detrimental to host defense mechanisms in the bronchoalveolar spaces . Exposure of HAM to O3 caused a concentration-dependent increase in release of prostaglandin E2 (PGE2), an important modulator of inflammation, phagocytosis, and oxidative burst . Although phagocytosis of particulate immune complexes was decreased by O3, we found no change in the quantity of Fc receptors and complement receptors on the HAM surface . Superoxide (O2-) production in response to phorbol ester was reduced after exposure of HAM to O3 while the basal O2- release in response to plastic adherence was not affected . Growth inhibition of the opportunistic yeast Cryptococcus neoformans by HAM was not affected by O3 exposure . The production of inflammatory mediators and immune modulators such as tumor necrosis factor-alpha, interleukin 1, and interleukin 6 were not induced by exposure to O3 . However, compared to controls, O3- exposed HAM produced significantly lower levels of these cytokines when stimulated with bacterial lipopolysaccharide (LPS) . Two-dimensional gel electrophoretic analysis of proteins made by HAM following in vitro exposure to O3 identified 11 proteins whose rate of synthesis was significantly altered . Thus, these studies show that exposure to O3 alters the functional competence of HAM . While there is a minimal effect on protein expression or synthesis, the responses of HAM to particulate immune complexes, to bacterial LPS, and to PMA are impaired . The release of arachidonic acid and PGE2 suggest that the effect of O3 is primarily targeted to the HAM cell membrane . These changes may ultimately result in increased susceptibility to inhaled infectious agents in the O3-exposed individual.

Am J Clin Pathol, 1991 Sep, 96(3), 377 - 80
The impact of a clinic for adults with HIV infection on the microbiology laboratory; McGowan JE Jr et al.; The Infectious Diseases Clinic (IDC) discussed serves adults who are seropositive for human immunodeficiency virus . The authors reviewed the outpatient and inpatient microbiology tests of a three-month period during 1989 for a systematic sample of IDC patients . The 249 patients in the sample had 682 microbiology tests performed during the period (mean 2.7 tests per patient) . Tests most frequently requested were mycobacterial culture, routine blood culture, and cryptococcal antigen determination . Patients with acquired immunodeficiency syndrome (43% of IDC patients) accounted for 63% of the requested IDC tests . IDC patients comprised about 2.4% of patients served but accounted for 3.9% of the requested microbiology tests and 6.6% of the microbiology work load for reported tests . Using Centers for Disease Control case projections, the authors estimated that services to IDC patients in 1993 would comprise 6.6% of all microbiology tests and 10.6% of the microbiology work load . The implications of these data for microbiology probably also apply to other laboratory testing and emphasize the need for more efficient ways to use and perform diagnostic studies required by patients with HIV infection.

Headache, 1991 Sep, 31(8), 518 - 22
Headache in HIV-1-related disorders; Lipton RB et al.; To define the causes, clinical significance and characteristics of headaches in HIV-1-related disorders, we studied 49 consecutive HIV-1 infected patients who presented with headache . Work-up included CT scans, cerebrospinal fluid examinations (in the absence of a contraindication) and serologic studies . Overall, 40 of 49 patients (82 percent) had an identifiable serious cause of headache . Cryptococcal meningitis (39 percent) and CNS toxoplasmosis (16 percent) were the leading headache etiologies . Serious causes were more likely in patients diagnosed with AIDS prior to presentation but also occurred in most patients in early stages of infection . Based on this study, we suggest that patients with HIV-1 infection must be managed with a high index of suspicion when they present with new onset headaches.

Antimicrob Agents Chemother, 1991 Sep, 35(9), 1721 - 5
Treatment of murine cryptococcal meningitis with an SCH 39304-amphotericin B combination; Albert MM et al.; Cryptococcal meningitis was induced in BALB/c mice by intracerebral infection with Cryptococcus neoformans . Drug therapy was initiated 1 day later, with mice receiving amphotericin B (AMB), SCH 39304, combination therapy, or no drug therapy (controls) . Most, but not all, combinations showed additive benefits, significantly prolonging survival and reducing organism counts in tissues compared with those in controls and groups which received the drugs independently . Optimum protection was obtained when a single dose of 10 mg of AMB per kg of body weight was combined with a fairly narrow SCH 39304 dose range . AMB antagonism did not occur with any regimen tested . AMB-azole combinations may be reasonable alternatives for patients who fail standard cryptococcosis therapeutic regimens.

J Thorac Imaging, 1991 Sep, 6(4), 28 - 35
Fungal disease in HIV-infected persons: cryptococcosis, histoplasmosis, and coccidioidomycosis; Stansell JD; The AIDS epidemic has profoundly influenced the expression of deep-seated fungal disease in this country over the past 10 years . Previously an uncommon etiology of life threatening disease, deep-seated fungal infections with Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis accounted for nearly 3000 AIDS index diagnoses in 1990 . As the epidemic matures, symptomatic HIV infection can be expected to rise in areas of endemic fungal infection resulting in further recognition of systemic fungal disease . Although amphotericin B and 5-flucytosine remain the initial treatments of choice for AIDS-associated deep fungal infection, clinical trials evaluating the new triazoles offer hope for more effective prophylaxis and treatment in the future.

Pediatr Infect Dis J, 1991 Sep, 10(9), 658 - 62
Extrapulmonary cryptococcosis in children with acquired immunodeficiency syndrome; Leggiadro RJ et al.; There is a paucity of published information available on extrapulmonary cryptococcosis (EC) in children infected with human immunodeficiency virus, the etiologic agent of the acquired immunodeficiency syndrome . We surveyed investigators in pediatric acquired immunodeficiency syndrome around the country regarding their experience with EC . Investigators from 33 (87%) of 38 institutions responded and information on 13 patients from 11 institutions was analyzed . EC was the acquired immunodeficiency syndrome indicator disease in 9 (69%) of 13 patients . Median age was 8 years with a range of 2 to 17 years . Human immunodeficiency virus risk factors were transfusion (5 patients), hemophilia (4 patients) and perinatal exposure (4 patients) . Meningitis, seen in 62% of patients, was the most common clinical manifestation . Although 2 patients with fulminant disease died before therapy was started, 10 (91%) of 11 had a clinical response to amphotericin B with or without flucytosine . Our study indicates a spectrum of EC in pediatric human immunodeficiency virus infection ranging from fulminant, fatal fungemia to chronic meningitis and fever of unknown origin . Cryptococcosis was generally not the cause of death in patients who initially responded to amphotericin B therapy . Optimal antifungal therapy, including the role of fluconazole, warrants further study.

Mayo Clin Proc, 1991 Sep, 66(9), 926 - 9
Cryptococcal meningitis manifesting as epilepsia partialis continua of the abdomen; Chalk CH et al.; We report a case of epilepsia partialis continua that primarily involved the abdominal muscles . Thorough assessment ultimately showed that the condition was due to cryptococcal meningitis . Surface electrode electromyography and electroencephalography were helpful in analyzing this unusual epileptic phenomenon . An 8-week treatment regimen of amphotericin B and a 30-day course of 5-fluorocytosine abolished the epilepsia partialis continua and cured the meningitis . This case should alert physicians to the fact that patients with epilepsia partialis continua may have clonic movements of only the trunk and that the spectrum of neurologic manifestations of cryptococcal infection must now include this seizure disorder.

J Intern Med, 1991 Sep, 230(3), 285 - 7
Isolated cryptococcosis of the adrenal gland; Liu YC et al.; A case of isolated adrenal cryptococcosis is reported . A patient with a history of diabetes mellitus had symptoms of left flank pain . Roentgenological and sonographic findings of the adrenal gland were indicative of a malignant tumour . Tissue obtained from surgery showed fungal granuloma and a poorly encapsulated cryptococcal organism was identified by special stains . A post-operative serum cryptococcal antigen test was positive, and the patient was successfully treated with surgery and a course of amphotericin B . After a 7-month follow-up period, there is no evidence of recurrence or dissemination.

Am J Med, 1991 Sep, 91(3), 267 - 72
Elevated cerebrospinal fluid pressures in patients with cryptococcal meningitis and acquired immunodeficiency syndrome; Denning DW et al.; Increased intracranial pressure has been a noteworthy problem in some of our patients with cryptococcal meningitis and acquired immunodeficiency syndrome (AIDS), and this appears to be a feature observed in patients with cryptococcal meningitis reported in the literature . Whereas most attention of clinicians is presently focused on optimizing the antifungal regimen, so as to improve on high failure rates in cryptococcal meningitis in AIDS, little attention has been paid to the problem of intracranial hypertension . We argue that visual loss and some of the cases of death early after the onset of chemotherapy may be related to high cerebrospinal fluid (CSF) pressure, regardless of antifungal therapy . The possible pathophysiologic mechanisms are discussed, and we postulate that the mechanism is reduced CSF outflow possibly due to increased outflow resistance, not necessarily accompanied by prominent cerebral edema . Optimal therapy of this complication is not yet established, but some measures that may be helpful are ventricular shunting, frequent high-volume lumbar punctures, and possibly glucocorticoids.

Am J Clin Pathol, 1991 Sep, 96(3), 381 - 4
Failure of dithiothreitol and pronase to reveal a false-positive cryptococcal antigen determination in cerebrospinal fluid; Sachs MK et al.; A patient with squamous cell carcinoma of the lung and a serum rheumatoid factor (RF) of 1:1,280 had a positive cerebrospinal fluid (CSF) latex agglutination test (LAT) for cryptococcal antigen, in culture-negative, India-ink-negative CSF . Pretreatment of the sample of CSF with 2-mercaptoethanol (2-ME) ablated the antigen titer and established the presence of a false-positive LAT, whereas CSF pretreated with dithiothreitol (DTT) and pronase continued to yield a false-positive result . The differing ability of pronase, DTT, and 2-ME to eliminate interfering substances from CSF has not been previously described . Moreover, because RF is unlikely to cross the blood-brain barrier, the authors postulated that malignant disease was responsible for the patient's false-positive LAT in CSF . Hence, the authors report the case to emphasize that false-positive LAT results in CSF are unlikely to be produced by RF and to underscore the benefit of using enzymatic and sulfhydryl-reducing agents when the validity of the initial test results are in doubt . Such a procedure will optimize the chances of accurately identifying false-positive LAT results in CSF.

Cell Immunol, 1991 Sep, 136(2), 448 - 61
Functional equivalence of cryptococcal and haptene-specific T suppressor factor (TsF) . II . Monoclonal anti-cryptococcal TsF inhibits both phagocytosis by a subset of macrophages and transfer of contact sensitivity; Blackstock R et al.; Monoclonal anti-cryptococcal TsF (which inhibits phagocytosis by macrophages) and anti-picryl TsF use the same two circuits to block the transfer of contact sensitivity (CS) . Both arm macrophages which then release a macrophage suppressor factor (MSF) when exposed to antigen . This MSF depresses the transfer of CS . The evidence suggests that a single molecular species of TsF (MW ca . 70 kDa), which bears an antigen-binding site and I-J determinant, is responsible for MSF production and inhibition of phagocytosis . Anti-cryptococcal TsF also arms the T acceptor cell which then releases nsTsF-1 after triggering with a specific antigen (SCPA) . This nsTsF-1, which depresses the transfer of contact sensitivity, was authentic, as shown by its I-J positivity (in contrast to MSF) and its role in the production of nsTsF-2 . As anti-picryl TsF also inhibits phagocytosis, it was concluded that anti-cryptococcal TsF, originally detected by the inhibition of phagocytosis, and anti-picryl TsF, originally detected by inhibition of CS, are functionally equivalent.

Cell Immunol, 1991 Sep, 136(2), 435 - 47
Functional equivalence of cryptococcal and haptene-specific T suppressor factor (TsF) . I . Picryl and oxazolone-specific TsF, which inhibit transfer of contact sensitivity, also inhibit phagocytosis by a subset of macrophages; Blackstock R et al.; Monoclonal and conventional cryptococcal-specific T suppressor factors (TsF) (also called TsFmp) depress phagocytosis by a subset of macrophages, while picryl- and oxazolone-specific TsF depress the passive transfer of contact sensitivity . This paper shows that these haptene-specific TsF also inhibit phagocytosis by a subset of macrophages and, using this assay, that the anti-haptene TsF resemble the anti-cryptococcal TsF in five respects: (i) the need for reexposure to specific antigen to trigger the release of TsF; (ii) genetic restriction in action; (iii) possession of an antigen-binding site; (iv) expression of I-J determinants; and (v) inactivation by reduction and alkylation . Purification of the anti-picryl TsF by sequential affinity chromatography indicates that the inhibition of phagocytosis is due to the TsF itself and not to a TsF-antigen complex . The TsF inhibits phagocytosis by a direct action as macrophages treated with TsF and exposed to antigen do not release a second factor which inhibits phagocytosis . These results and those of the accompanying paper indicate that the anti-cryptococcal and anti-haptene TsF are functionally equivalent, antigen-specific suppressor factors.

Infect Immun, 1991 Sep, 59(9), 3101 - 10
Early events in initiation of alternative complement pathway activation by the capsule of Cryptococcus neoformans; Kozel TR et al.; The capsule of Cryptococcus neoformans is a powerful activator of the alternative complement pathway . This study examined the manner in which the cryptococcal capsule influences initiation of and early events in complement activation by C . neoformans . These studies examined the effects of the classical and alternative pathways on the kinetics and early sites for deposition of C3 fragments on encapsulated cryptococci, nonencapsulated cryptococci, and zymosan . The results showed that nonencapsulated cryptococci and zymosan are qualitatively and quantitatively similar in the manner in which they initiate complement activation . Both utilize the classical and alternative pathways . Initiation via the classical pathway occurs suddenly and simultaneously at sites distributed over the entire cell surface . Initiation of the alternative pathway by zymosan and nonencapsulated cryptococci is characterized by a lag of 6 to 8 min before appreciable amounts of C3 accumulate on the cells . Alternative pathway initiation by zymosan and nonencapsulated cryptococci occurs at a limited number of focal initiation sites that expand with alternative pathway amplification to cover the cell surface . Presence of the cryptococcal capsule blocks classical pathway initiation, which would normally occur at the cryptococcal cell wall, and produces an initiation that is dependent solely on the alternative pathway . Initiation of the alternative pathway by the cryptococcal capsule is characterized by a lag in C3 accumulation and the appearance of a limited number of focal initiation sites which resemble those observed when the alternative pathway is activated by zymosan and nonencapsulated cryptococci.

Mycoses, 1991 Sep-Oct, 34(9-10), 401 - 4
Effect of flucytosine on renal function in the rat; Heidemann HT et al.; Flucytosine (5-fluorocytosine), a potent antimycotic drug against various systemic infections such as candidosis, aspergillosis and cryptococcosis, is extensively excreted by the kidneys, yet its possible role in renal function is not known . In the present study flucytosine, administered intravenously, increased significantly renal blood flow (RBF) by 26% from 5.06 +/- 0.9 ml/min/kidney . The renal vasodilation was combined with an elevation of creatinine clearance of 140% from a baseline value of 0.23 +/- 0.11 ml/min/kidney . This improvement in renal function was accompanied by an increase in filtration fraction, urine volume and potassium excretion . In comparison, rats administered an equal amount of 5% glucose only showed no changes in the values of these parameters.

Mycoses, 1991 Sep-Oct, 34(9-10), 377 - 9
Infection due to Cryptococcus neoformans of unusual morphology in a patient with AIDS; Anandi V et al.; Cryptococcus neoformans with a rare morphology of hand-mirror appearance was demonstrated by direct microscopic preparation of both cerebrospinal fluid (CSF) and sputum of a patient with AIDS . In addition, one to six blastoconidia were seen at the tip of a germ-tube like structure . Cr . neoformans was isolated in pure culture and the identification was confirmed by biochemical and serological tests as well as by animal pathogenicity.

J Med Assoc Thai, 1991 Sep, 74(9), 421 - 2
Cryptococcal meningitis in pregnancy: a case report; Chotmongkol V et al.; We report a pregnant woman with cryptococcal meningitis . She experienced symptoms of meningitis before gestation which worsened during pregnancy . Combined treatment of amphotericin B and flucytosine, including ventriculo-peritoneal shunt gave a favorable outcome for both the patient and her child . We suggest that pregnant women with cryptococcal meningitis should continue their pregnancy and prefer to use combination of both drugs in standard doses because of the effectiveness, shorter duration of treatment and less toxicity than amphotericin B alone.

Acta Pathol Jpn, 1991 Sep, 41(9), 673 - 9
Use of patients' sera for immunoperoxidase demonstration of infectious agents in paraffin sections; Tsutsumi Y et al.; Using patients' sera diluted from 1:10 to 1:1,000 as the primary antibodies in indirect immunoperoxidase staining, the authors visualized a variety of infectious agents in formalin-fixed, paraffin-embedded tissue sections . The target lesions included 1) pyoderma caused by Staphylococcus aureus, 2) cryptococcal infection, 3) dermal sporotrichosis, 4) colon ulcer caused by amebic dysentery, 5) cutaneous leishmaniasis, and 6) chronic liver abscess containing ova of Ascaris lumbricoides . The infectious agents were clearly identified in the respective lesions . Paraffin sections of other kinds of infectious lesions served as controls to clarify the specificity of the immunostaining . While the sera of patients with bacterial and fungal infection showed a wide range of cross-reactivity against bacteria and/or fungi, those with parasitic infection exhibited a relatively good specificity for the pathogen . Almost no immunoreactivity of endogenous human IgG in the paraffin sections was demonstrated under the conditions of this study . This approach can be used in diagnostic pathology, particularly when specific heteroantisera or monoclonal antibodies are unavailable.

J Clin Microbiol, 1991 Sep, 29(9), 1883 - 7
Normally saprobic cryptococci isolated from Cryptococcus neoformans infections; Krajden S et al.; We report two cases in which Cryptococcus laurentii was isolated from surgically resected pulmonary lesions but the cryptococcal cells is tissue reacted positively with a specific fluorescent antibody (FA) conjugate for Cryptococcus neoformans . Both patients had no apparent host defense defects . In both cases, multiple cryptococcal isolates were obtained from tissue, and yeastlike cells consistent with C . neoformans were seen in direct histology . The isolates were identified by assimilation patterns and standard procedures including phenoloxidase reactions . Since C . laurentii was consistently isolated by using stringent procedures, it was considered unlikely that the fungus represented surgical or laboratory contamination . Its presence may be the result of dual infection not detected by FA, but other possible explanations exist . The results show the value of the FA test in diagnostic mycology and call into question previous reports of cryptococci other than C . neoformans as agents of infection.

Nihon Kyobu Shikkan Gakkai Zasshi, 1991 Sep, 29(9), 1174 - 9
{The defensive role of human pulmonary alveolar macrophages and polymorphonuclear leukocytes against a strongly or weakly virulent strains of Cryptococcus neoformans}; Tabeta H et al.; The phagocytic and killing activities of human pulmonary alveolar macrophages (PAM) and polymorphonuclear leukocytes (PMN), and superoxide (O2-) production in phagocytizing PAM and PMN were studied by using a strongly and weakly virulent strains of Cryptococcus neoformans (C . neoformans) in mice . The strongly virulent strain was encapsulated with a thick capsule while the other had a thin one . The phagocytic and killing activities of PAM and PMN against the strongly virulent strain were lower than against the weakly virulent one . There was no significant difference between PAM and PMN in terms of phagocytic or killing activities and O2- production . It seems likely that O2- plays no defensive role in the intracellular killing of C . neoformans by PAM and PMN because no correlation was found between the killing activity and O2- production . These results indicate that human PAM and PMN play an effective role in host defense against the weakly virulent strain of C . neoformans encapsulated with a thin capsule but are not effective against the strongly virulent strain encapsulated with a thick capsule.

Medicine (Baltimore), 1991 Sep, 70(5), 326 - 43
The causes of death in patients with human immunodeficiency virus infection: a clinical and pathologic study with emphasis on the role of pulmonary diseases; McKenzie R et al.; The clinical records and autopsy data of 75 patients dying with AIDS were reviewed to determine the frequency of individual diseases diagnosed premortem and postmortem, the significance of pulmonary processes found in the lungs at autopsy, and the clinical and pathologic causes of death . Cytomegalovirus (CMV) infection was identified histologically either premortem or postmortem in 81% of patients . The lungs and adrenal glands were infected most commonly . Only one-half of CMV infections were recognized premortem . Pneumocystis pneumonia and Kaposi sarcoma occurred in 68% and 59% of patients, respectively, but were not unsuspected premortem in any patient . Visceral involvement with Kaposi sarcoma, however, was frequently recognized only at autopsy . While disseminated M . avium-intracellulare infection was common (31% of patients), histologically documented pulmonary disease was uncommon (3% of patients) . Cryptococcal infection, diagnosed in 10 patients, was confined to the central nervous system in only 1 patient . Toxoplasma, in contrast, infected the brain of only 6 patients . All 75 patients had one or more disease processes identified in their lungs or pleurae at autopsy . These processes included opportunistic infections in 76% of patients, neoplasms in 37% (Kaposi sarcoma in 36% and lymphoma in 3%), and other processes in 60% . The most prevalent pathogen, CMV was found in pulmonary tissue from 44 patients and caused significant disease in 21 patients . Five patients died due to CMV pneumonia . Pneumocystis carinii was found at autopsy in 24 patients . In spite of treatment, pneumocystis pneumonia was fatal in 11 patients . One patient died with concomitant CMV and pneumocystis pneumonia . Kaposi sarcoma, identified in the lungs of 23 patients, led to death in 5 patients via upper airway obstruction, hemorrhage, or parenchymal destruction . Other fatal pulmonary processes included bacterial pneumonia in 9 patients, idiopathic diffuse alveolar damage in 5, cryptococcosis in 2, and pulmonary hemorrhage in 1 . Specific clinical criteria were used to determine the cause of death due to organ system failure . Fifty-one percent of patients died due to respiratory failure; 16% from neurologic disease; 17% from hypotension that was not caused by respiratory, neurologic, or cardiac disease; and 3% from cardiac dysfunction . Thirteen percent of deaths did not meet the clinical criteria defining these 4 categories . This clinical assessment was combined with autopsy data to identify specific diseases as causes of death.(ABSTRACT TRUNCATED AT 400 WORDS)

Orv Hetil, 1991 Aug 25, 132(34), 1851 - 6, 1859
{Opportunistic systemic mycoses}; Szalka A et al.; Systemic fungal infections can be primary or opportunistic . The mycoses caused by opportunistic pathogens become increasingly more important . These infections are mainly caused by Candida species, Aspergillus species, Cryptococcus neoformans, Mucor etc . The predisposing factors to these diseases are numerous: neutropenia, organ transplantation, use of steroids, broad spectrum antibiotics, antineoplastic chemotherapy, parenteral nutrition, prolonged intravenous infusions, extensive surgery etc . Mortality is high because many fungal infection are difficult to diagnose, especially in their early, more treatable stages . Considerable progress in treating these infections has been achieved . Systemic fungal infections, however, continue to present major problems, including clinical resistance, microbial resistance, emergence of new pathogens and involvement of more susceptible patients . The purpose of this paper is to review the recent progress and current problems in diagnosis, treatment and prevention of opportunistic systemic fungal infections.

J Leukoc Biol, 1991 Aug, 50(2), 151 - 9
Role of natural killer cells in resistance to systemic cryptococcosis; Salkowski CA et al.; These studies demonstrate that Cryptococcus neoformans infection induced a dose-dependent augmentation of splenic natural killer (NK) cell activity by bg/+, but not bg/bg mice . To directly assess the role of NK cells in resistance to C . neoformans, bg/+ and bg/bg mice were treated with anti-NK-1.1 monoclonal antibody (mAb) . Anti-NK-1.1-treatment abrogated the augmented NK cell activity observed during C . neoformans infection in bg/+ mice . Anti-NK-1.1-treated bg/+ mice had higher C . neoformans colony forming units (CFU) in their lungs on days 3 and 7 after intravenous (i.v.) challenge than control bg/+ mice . Moreover, the number of C . neoformans CFU in the lungs of anti-NK-1.1-treated bg/+ mice on days 3 and 7 were similar to those observed for infected bg/bg mice . By day 14, however, no differences in C . neoformans CFU were evident in the lungs of anti-NK-1.1-treated and control bg/+ mice . Anti-NK-1.1-treatment did not alter either the growth of C . neoformans in the spleens, livers, kidneys, or brain of bg/+ mice or the susceptibility of bg/bg mice to systemic cryptococcosis . These studies suggest that NK cells do not play a role in resistance to systemic cryptococcosis in the spleen, but do appear to play an early, but transient role in resistance to C . neoformans in the lungs . Overall, congenital defects in polymorphonuclear neutrophils (PMNs) and macrophages (M phi s), in addition to defects in NK cells, contribute to the enhanced susceptibility of bg/bg mice to systemic cryptococcosis.

J Rheumatol, 1991 Aug, 18(8), 1254 - 6
Pneumocystis carinii pneumonia associated with methotrexate therapy in rheumatoid arthritis; Flood DA et al.; Opportunistic infections occur in patients with rheumatic diseases treated with low dose methotrexate (MTX) with or without other immunosuppressants . Our case report illustrates a fatal case of Pneumocystis carinii pneumonia in a patient with rheumatoid arthritis treated with low dose MTX and glucocorticoid . A review of the literature reveals other opportunistic infections such as Cryptococcus, Nocardia, and herpes zoster presenting in such patients . These occurrences suggest that MTX should be used cautiously in patients with rheumatic disease receiving concomitant medical therapy.

Immun Infekt, 1991 Aug, 19(4), 116 - 20
{Therapy of systemic mycoses in immunodeficiency}; Just-Nubling G et al.; Fungal infections have gained importance recently . The major reason for this is the increasing number of patients with immunodeficiency . Systemic treatment of invasive fungal infections up to now has been based on relatively few antimycotic agents (amphotericin B, flucytosine, as well as the azole derivatives fluconazole and itraconazole) . Only a few number of fungi cause the majority of opportunistic fungal infections . Candida albicans leads to severe mucosal infections in cases of immunodeficiency . Systemic mycoses usually present as endogenous infections or are caused by an infected central venous catheter with dissemination into multiple organs . Less severe candida infections should be treated with fluconazole . A more severe candida infection still requires treatment with amphotericin B plus flucytosine . Aspergillus fumigatus, a ubiquitous mold, is the most frequent pathogen in patients with granulocytopenia . First choice treatment also is amphotericin B and flucytosine; treatment should be started despite lacking proof of pathogen in patients with immunodeficiency and typical clinical signs . Itraconazole, the azole derivative active against aspergillus, may be administered only in mild cases of aspergillus infections in immunocompromised patients . Infections with Cryptococcus neoformans, which hardly ever occur, have been observed frequently in AIDS patients . The manifestation of cryptococcosis mainly presents as chronical meningitis . Presently various treatment concepts are being clinically tested . An initial combination of amphotericin B, flucytosine, and fluconazole, followed by long-term treatment with fluconazole, is recommended.

FEMS Microbiol Lett, 1991 Aug 1, 66(2), 153 - 6
A newly described role for protein glycosylation: starved yeast cells absorb their under-glycosylated secreted xylanase faster than the glycosylated enzyme; Morosoli R et al.; The yeast Cryptococcus albidus secretes a highly glycosylated xylanase into the culture medium, when grown in presence of xylan, but addition of tunicamycin to the medium results in the formation of an underglycosylated xylanase . Both types of enzyme preparation were incubated with starved yeast cells . Assimilation of the xylanases by the cells over a period of time was followed by electron microscopy using immunolocalization with anti-xylanase antibodies coupled to gold-labelled protein A . Electron micrographs showed that the glycosylated enzyme mostly remained attached to the cell wall surface, while the underglycosylated enzyme not only surrounded the cell wall but was also present in the hyaloplasm, indicating its assimilation by the cells . These experiments indicate that the carbohydrate moiety of the xylanase protects the enzyme from its assimilation by the cells producing it.

Am J Med Sci, 1991 Aug, 302(2), 129 - 32
Fluconazole: a new triazole antifungal agent; Morrow JD; Fluconazole is a recently approved agent for the treatment of certain fungal infections . Based on available studies, the drug is clearly effective in oropharyngeal candidiasis in immunosuppressed hosts . Current evidence suggests it may be more efficacious than other azole drugs for oropharyngeal disease . It is probably also effective in other infections due to Candida species, but controlled studies are lacking . Fluconazole is also efficacious in the treatment of cryptococcal meningitis, but recent reports question its use as initial therapy in HIV-infected patients with this illness . The drug, however, is clearly more effective than amphotericin B in the suppression of cryptococcal meningitis in AIDS patients and is the treatment of choice in this situation.

Curr Opin Dent, 1991 Aug, 1(4), 423 - 8
Oral lesions in the systemic mycoses; de Almeida OP et al.; Oral lesions have rarely been reported in systemic mycoses, though over the past few years they have been recorded particularly in immunocompromised individuals . The dramatic increase in numbers of immunocompromised persons, especially those infected with human immunodeficiency virus, has almost certainly been responsible for the increase in reports of oral disease caused by systemic mycoses, particularly aspergillosis, cryptococcosis, and histoplasmosis . However, reports of coccidioidomycosis, blastomycosis, and paracoccidioidomycosis have, as yet, increased little in this population . Dentists, when they observe chronic oral ulceration, chronic maxillary sinus infection, or bizarre mouth lesions (particularly in immunocompromised patients) should be aware of the possibility of a systemic mycosis . Amphotericin remains the standard therapy for most deep mycoses, while the newer azoles are the first-line agents for superficial mycoses, such as candidiasis, and are increasingly used in the deep mycoses.

J Clin Microbiol, 1991 Aug, 29(8), 1665 - 9
Rapid clearance of Candida albicans mannan antigens by liver and spleen in contrast to prolonged circulation of Cryptococcus neoformans antigens; Kappe R et al.; Clearances of mannan antigen from Candida albicans and glucuronoxylomannan antigen from Cryptococcus neoformans were examined in nonimmune rabbits by using self-prepared latex agglutination tests . Injected intravenously, 20 mg of Candida mannan antigen was cleared from the serum with a half-life of approximately 2 h . In contrast, 20 micrograms of Cryptococcus glucuronoxylomannan antigen had a half-life in serum of approximately 24 h . At the latest, 9 h after injection, both antigens were no longer detectable without pretreatment of serum samples with protease and heating to 100 degrees C, thus indicating rapid binding by serum proteins other than immunoglobulins . Candida mannan antigen clearance was also examined in nonimmune mice after intravenous injection of (i) 200 micrograms of Candida mannan antigen, which accumulated in the liver and spleen and persisted for 97 days; (ii) 2 x 10(7) ethanol-killed Candida blastospores, which was accompanied by rapid clearance of mannan from the blood but accumulation of mannan in the liver and spleen and slow clearance from these organs; (iii) 6 x 10(6) viable C . albicans cells (lethal infection), which resulted in a rapid decrease of Candida CFU in the blood, liver, and spleen during the first 8 h, after which blood cultures were negative on day 2 and viable Candida burdens in the liver and spleen persisted at 10(5) CFU/g, whereas Candida mannan antigen continued to circulate in the bloodstream and accumulated in the liver and spleen.

J Clin Microbiol, 1991 Aug, 29(8), 1616 - 9
Comparison of the PREMIER cryptococcal antigen enzyme immunoassay and the latex agglutination assay for detection of cryptococcal antigens; Gade W et al.; A new enzyme immunoassay (EIA), PREMIER Cryptococcal Antigen, was compared with latex agglutination (LA) for the detection and quantitation of circulating capsular polysaccharide antigen from Cryptococcus neoformans . The clinical evaluation of PREMIER EIA as a screening assay, including 475 specimens with 120 LA and EIA positives, resulted in 99% sensitivity and 97% specificity . The clinical specimens included sera and cerebrospinal fluids as well as 10 rheumatoid factor-positive and 20 anti-nuclear antibody-positive serum samples . This monoclonal antibody-based assay detects serotypes A to D at 0.63, 0.63, 7.8, and 62 ng/ml, respectively . With three different known positive specimens, the assay was found to yield coefficients of variation of 2 to 12% for intra- and interassay comparisons of precision and reproducibility . The primary use for semiquantitative values derived with the LA or EIA is to follow the course of disease and monitor drug therapies . The present data suggest that the PREMIER EIA will be a valuable method for this purpose . We conclude that the PREMIER Cryptococcal Antigen EIA provides a rapid, convenient, and reliable antigen detection method for screening and semiquantitative determination of antigen levels.

Zentralbl Bakteriol, 1991 Aug, 275(3), 390 - 3
The discovery of creatinine assimilation in Cryptococcus neoformans, and subsequent work on the characterization of the two varieties of C . neoformans; Kwon-Chung KJ; The discovery of creatinine assimilation in C . neoformans by Staib served as the foundation for our biochemical, genetical, ecological, epidemiological and taxonomic studies on the two varieties of C . neoformans for the past 15 years . The two varietal concept is now widely accepted and the arrival of AIDS epidemic has promoted the recognition of the differences between the two varieties, especially in their epidemiology and ecology . Since the agent of cryptococcosis in AIDS patients almost always belongs to the var . neoformans even in geographical areas prevalent for var . gattii, it is important to study the possible differences in the pathogenesis of the two varieties.

Arch Intern Med, 1991 Jul, 151(7), 1295 - 303
Human immunodeficiency virus infection and the skin; Cockerell CJ; The skin is commonly affected in the course of human immunodeficiency virus (HIV) infection . In many cases, skin findings may be the earliest sign of HIV disease or acquired immunodeficiency syndrome . When cutaneous diseases occur in unusual settings, such as zoster in a young individual, are increased in severity or fail to respond to routine therapy, the possibility of underlying immunodeficiency should be suspected . Skin diseases in HIV-infected hosts include primary infections, such as those caused by herpes simplex virus and molluscum contagiosum, as well as secondary involvement of systemic diseases, such as cryptococcosis and histoplasmosis . Noninfectious inflammatory processes, such as seborrheic dermatitis and psoriasis, as well as neoplasms, such as Kaposi's sarcoma and basal cell carcinoma, may all be seen in these patients . We review a number of these diseases and discuss their treatment . Clinicians must be aware of the cutaneous manifestations of HIV infection so that the disease will be recognized at an earlier point in time and therapy with zidovudine and prophylactic antibiotics will be instituted where appropriate.

Infect Immun, 1991 Jul, 59(7), 2291 - 6
Inhibition of Cryptococcus neoformans replication by nitrogen oxides supports the role of these molecules as effectors of macrophage-mediated cytostasis; Alspaugh JA et al.; Activated macrophages are able to inhibit the replication of intracellular microbes and tumor cells . In the murine system, this cytostatic effect is associated with the oxidation of L-arginine to L-citrulline, nitrite, and nitrate and is thought to be mediated by an intermediate of this reaction, possibly nitric oxide (NO.) . By exposing replicating Cryptococcus neoformans cells to conditions under which NO . is chemically generated, we have observed a cytostatic effect similar to that caused by activated murine macrophages . Nitric oxide is formed as a decomposition product of nitrite salts in acidic, aqueous solutions . Although C . neoformans replicates well in the presence of high nitrite concentrations at physiologic pH, its growth in acidic media can be inhibited by the addition of low concentrations of sodium nitrite . The degree of cytostasis is dependent on both the pH and the nitrite concentration of the NO . generating solution . The cytostatic effector molecule appears to be a gas since, in addition to inhibiting C . neoformans replication in solution, it is able to exert its inhibitory effect across a gas-permeable but ion-impermeable membrane . At high nitrite concentrations, a fungicidal effect occurs . We propose that the growth inhibition of C . neoformans upon exposure to chemically generated NO . or some related oxide of nitrogen represents a cell-free system simulating the cytostatic effect of activated murine macrophages.

J Antimicrob Chemother, 1991 Jul, 28 Suppl A, 67 - 82
Clinical management of fungal infection in patients with AIDS; Shaunak S et al.; The frequency of disseminated fungal infection in patients with the Acquired Immune Deficiency Syndrome (AIDS) has provided a major impetus for the reevaluation of standard antifungal protocols as well as accelerating the development and clinical testing of new agents . As a result, useful clinical guidelines regarding the use of amphotericin B and flucytosine in cryptococcosis are beginning to emerge that relate specifically to patients with AIDS . Oral agents, most notably fluconazole have shown promise and are now being evaluated in controlled clinical trials . Histoplasmosis and coccidioidomycosis have emerged as significant infections and pose new problems in both diagnosis and management . Although amphotericin B and flucytosine must still be used for induction therapy in patients with these infections, preliminary studies of itraconazole suggest that it could be useful for maintenance therapy . Despite there being considerably less clinical experience with histoplasmosis and coccidioidomycosis than with cryptococcosis, it is hoped that the lessons learnt with cryptococcosis will accelerate the development of new diagnostic assays and improved therapeutic approaches.

J Antimicrob Chemother, 1991 Jul, 28 Suppl A, 35 - 46
Antifungal therapy and the new azole compounds; Hay RJ; At present there are weaknesses in the range and scope of antifungal chemotherapy . The development of a new group of azole drugs, the triazoles, has introduced antifungal agents with broad-spectrum activity which can be given by the oral route . Fluconazole is very well absorbed and has good penetration . While its principal activity is against yeasts and there are clinical data to support its use in candida and cryptococcus infections, little work has been completed on its clinical use in aspergillosis . Itraconazole is less well absorbed, but highly bound in tissue . Its spectrum of activity is somewhat broader than that of fluconazole and it is clinically active against superficial mycoses and some of the infections caused by pathogenic fungi such as Histoplasma capsulatum . There is some early evidence of efficacy in aspergillosis but more studies are required in neutropenic patients . Both drugs show promise but comparative assessments are sorely needed.

J Antimicrob Chemother, 1991 Jul, 28 Suppl A, 13 - 22
The clinical presentation and diagnosis of invasive fungal infections; Maartens G et al.; The frequency of invasive fungal infections is increasing owing to the increasing numbers and improved survival of immuno-compromised patients . The fungi responsible for these infections are predominantly opportunistic pathogens . The clinical features and diagnosis of the four commonest infections (invasive candidosis and aspergillosis, cryptococcosis and mucormycosis) are discussed . Particular emphasis is given to the identification of risk factors for these infections, which are different for each disease . As these organisms are common contaminants or commensals, definitive diagnosis requires culture from sites that are normally sterile or histological demonstration of tissue invasion . Definitive diagnosis is not always possible, in part owing to the severe nature of patients' underlying illnesses . A high proportion of cases are diagnosed post mortem because of difficulties in establishing a diagnosis . Clinical diagnoses thus need to be made early in the course of these infections, but a high index of suspicion and knowledge of the clinical manifestations are required.

J Antimicrob Chemother, 1991 Jul, 28 Suppl A, 1 - 11
Opportunistic and pathogenic fungi; Richardson MD; The number of fungal species reported to cause disease in man is increasing rapidly . Very few of these fungi are capable of infecting a normal host . Important progress has been achieved in an understanding of fungal pathogenicity including the mechanisms of adherence to host tissues, penetration of tissues, multiplication within the host, and the interaction of fungal cells with host effector cells . In addition to the increase in infections by opportunistic and pathogenic fungi in compromised patients, caused by Candida spp., Aspergillus spp., Cryptococcus neoformans, Histoplasma capsulatum and Coccidioides immitis, many fungi that occur as saprophytes in the environment and which had previously been considered to be nonpathogenic are now being encountered as causes of human infection . The advent of these unusual infections has led to reappraisal of the diagnostic tests involved in the investigation of fungal infections and has had important implications for the choice of treatment . Many of these fungi have a similar tissue appearance and the organisms must be isolated and identified to ensure that the most appropriate treatment is given.

Antimicrob Agents Chemother, 1991 Jul, 35(7), 1460 - 3
Treatment of experimental cryptococcosis with SCH 39304 and fluconazole; Negroni R et al.; The efficacy of two triazoles, SCH 39304 and fluconazole, in the treatment of disseminated cryptococcosis in Wistar rats was determined . A total of 160 rats were inoculated intracardiacally with 2 x 10(5) cells of Cryptococcus neoformans . Both drugs were administered by gavage once daily, at three doses (8, 16, and 32 mg/kg/day) . Two treatment schedules were followed: (i) treatment began 1 week after infection and continued for 3 weeks and (ii) prophylaxis treatment began 3 days before infection and continued an additional 3 weeks . Evaluation was based on (i) macroscopic examination of lungs, (ii) microscopic examination of brains and lungs, (iii) histopathology of brains and lungs, and (iv) determination of number of CFU in brains . The number of CFU was the best measure of activity . SCH 39304 was more active than fluconazole in both regimens, and, prophylactically, SCH 39304 was able to achieve biological cures.

Protein Seq Data Anal, 1991 Jul, 4(1), 15 - 20
The primary structure of xylanase from Thermoascus aurantiacus; Srinivasa BR et al.; The amino acid sequence of xylanase isolated from the culture medium of Thermoascus aurantiacus was determined . It had 269 amino acid residues with an alpha-N-acetyl group at the amino terminus . The structure of blocked N-terminal 11 amino acid tryptic peptide except for acetylalanine was determined by sequence analysis of peptides derived from partial acid hydrolysis and from thermolysin digestion . The blocked N-terminal amino acid was determined as N-acetylalanine by electron ionization mass spectrometry . The sequence comparison of xylanase from T . aurantiacus with the xylanases of alkalophilic Bacillus sp C-125 and Cryptococcus albidus showed 40% similarity . Xylanase from T . aurantiacus had up to 15% similarity with the other two xylanases known . All the five xylanases showed a higher degree of similarity at the level of secondary structure.

Am J Respir Cell Mol Biol, 1991 Jul, 5(1), 19 - 26
Interferon-gamma activates rat alveolar macrophages for anticryptococcal activity; Mody CH et al.; Cryptococcus neoformans is a pathogenic yeast causing disease predominantly in immunosuppressed patients . C . neoformans is acquired by the pulmonary route, where the alveolar macrophage (AM) is a resident mechanism of host defense . The ability of rat AM to be activated by products of the immune response for enhanced anticryptococcal effect has not previously been demonstrated . Rat AM could be activated in vitro for anticryptococcal activity by medium conditioned by concanavalin A-stimulated splenic lymphocytes . A monoclonal antibody that neutralizes interferon-gamma (IFN-gamma) inhibited the macrophage-activating activity of lymphokine-containing medium (LCM) . Further, recombinant IFN-gamma activated AM for anticryptococcal activity . The concentration of IFN-gamma in LCM, determined by enzyme-linked immunosorbent assay, was equivalent to the range of concentrations of recombinant IFN-gamma which activated AM . Thus, IFN-gamma was necessary and sufficient for optimal macrophage activation by medium conditioned by proliferating lymphocytes . Lipopolysaccharide could not enhance the anticryptococcal activity produced by optimal concentrations of LCM or IFN-gamma but did augment the effects of submaximal stimulation . Both LCM and recombinant IFN-gamma increased the percentage of macrophages with cell-associated cryptococcus, suggesting that activation of AM enhanced the adhesion or uptake of cryptococcus . We speculate that inadequate availability of lymphokines such as IFN-gamma may result in the immunodeficient state in hosts unable to generate an appropriate response to cryptococcal antigens . Administration of lymphokines such as IFN-gamma to immunosuppressed hosts might circumvent the defect in cell-mediated immunity.

J Infect, 1991 Jul, 23(1), 17 - 31
Cost implications of alternative treatments for AIDS patients with cryptococcal meningitis . Comparison of fluconazole and amphotericin B-based therapies; Buxton MJ et al.; The extra demands placed upon health care resources by management of AIDS patients have increased the focus on cost implications of therapeutic alternatives . Cryptococcal meningitis is a common life-threatening infection in AIDS patients, usually treated with amphotericin B, often in combination with flucytosine . Administered intravenously, this therapy is associated with frequent and often severe side effects . Fluconazole is a new alternative which can be given orally once daily and has fewer such side effects . The purpose of this study was to examine the cost implications of these different therapies for both primary and maintenance treatment of cryptococcal meningitis . Comparison of these two therapies in recent clinical trials has indicated that fluconazole is at least as effective as amphotericin B, and therefore cost-minimisation analysis is an appropriate method to study the economic consequences of the alternative treatments . Patient management and resource-use information for both treatments was obtained using a modified Delphi technique with a panel of European physicians experienced in the treatment of this disease, and three models were developed to reflect the variability of practice evident among the panel members . U.K . health care costs were used to value these resources . The results indicated that, despite the higher cost of the drug itself, the costs associated with fluconazole were likely to be markedly less than those for amphotericin B for primary treatment, and similar or slightly cheaper for maintenance treatment . Over 1 year of treatment, the saving from the use of fluconazole would be in the range of 4000-14,000 pounds.

N Y State J Med, 1991 Jul, 91(7), 292 - 6
Optimal therapy of cryptococcosis in patients with the acquired immunodeficiency syndrome; Chechani V et al.; Although amphotericin B (AB) is the primary therapeutic agent for cryptococcosis complicating the acquired immunodeficiency syndrome (AIDS), the total dose administered is extremely variable, and the end point of therapy has not been well defined . Since these patients require life-long suppressive therapy following the primary therapy, the definition of treatment "end point" becomes crucial . To delineate more effective treatment approaches, we reviewed the medical records of 48 patients with cryptococcosis complicating AIDS . Fever (81%) and headache (77%) were the predominant symptoms . A clinical response to AB (defervescence and resolution of symptoms) was noted in 46% of the febrile patients . The cumulative AB dose administered to the time of clinical response was variable (0.1-1.76 g), but was noted early in the majority of the patients (less than 0.4 g) . Repeat fungal cultures from the initial positive site for Cryptococcus neoformans (CN), obtained after observation of the clinical response, were negative in 7/7 patients . Nosocomial bacterial infections were quite common and often complicated intravenous AB therapy . Bacteremias were documented in 10/14 febrile episodes occurring during AB therapy in the 22 patients with an initial clinical response . Bacteremias were identified in 6/21 patients who failed to defervesce with AB therapy . Staphylococcus aureus (N = 9) and Salmonella species (N = 2) were the most common pathogens causing bacteremia . An algorithm for the treatment of cryptococcosis complicating AIDS may shorten the duration of primary intravenous AB therapy . This might reduce secondary infectious complications and the costs of hospitalization.

Mycoses, 1991 Jul-Aug, 34(7-8), 319 - 22
Effect of culture media on in vitro susceptibility testing of fluconazole against some yeasts; Sekhon AS et al.; Thirty clinical isolates, comprising six strains of Candida albicans, and four strains each of C . lusitaniae, C . parapsilosis, C . tropicalis, Cryptococcus neoformans, Torulopsis glabrata and Trichosporon beigelii were tested against fluconazole, using Sabouraud's dextrose (SD) broth and a high resolution (HR) medium (Pfizer Central Research, Inc.) . The procedure was a standard tube (1 ml/tube) dilution, and C . albicans Y01 09 was included as a reference strain to monitor quality and reproducibility . Results indicated that the minimum inhibitory concentrations (MICs) for all isolates of C . albicans, C . lusitaniae, C . tropicalis, and Tr . beigelii were 100 micrograms ml-1 or greater in the SD medium . In the HR medium, however, the MICs for two isolates of C . albicans were 1.56 micrograms ml-1, in other four gave higher values (greater than 100 micrograms ml-1), and the results for C . lusitaniae and Tr . beigelii were in the range 1.56-3.12 micrograms ml-1 . The MICs for C . tropicalis were unaffected (100 micrograms ml-1) by the medium used . All Cr . neoformans isolates yielded a uniform value (1.56 micrograms ml-1) in HR medium as compared to somewhat more variable results (MICs 0.39-1.56 micrograms ml-1) in SD broth . The MICs for T . glabrata in the SD and HR media were 3.12-12.5 and 6.25 micrograms ml-1, respectively . The data indicated that the HR medium is preferable for the in vitro susceptibility testing of C . albicans, C . lusitaniae and Tr . beigelii to fluconazole . The MICs for other yeasts were not affected by the culture medium . The reference C . albicans isolate yielded an MIC of 1.56 micrograms ml-1 throughout.

Mycoses, 1991 Jul-Aug, 34(7-8), 313 - 6
Feline meningitis due to Cryptococcus neoformans var . neoformans and review of feline cryptococcosis; Pal M; Cryptococcus neoformans var . neoformans was ascertained as the prime cause of fatal meningitis in a young-adult female domestic cat who was suspected of rabies . The pathogen was isolated in heavy growth from the infected brain specimen on simplified sunflower seed (Helianthus annuus) medium at 30 degrees C . Periodic acid-Schiff stained impression smear revealed numerous cryptococcal cells . Histologically, pia-arachnoid showed thickening along with many circular yeast cells with and without budding morphologically consistent with Cr . neoformans . The detailed typing of the strain indicated that it belonged to serotype AD and Filobasidiella neoformans var . neoformans mating type 'alpha' . The emphasis is given on early diagnosis by immunological and mycological techniques and prompt chemotherapy to avert the fatal consequences of this enigmatic mycosis.

Mycoses, 1991 Jul-Aug, 34(7-8), 309 - 11
Cutaneous cryptococcosis as the first symptom of a disseminated cryptococcosis in a patient with lymphogranulomatosis X; Konig M et al.; A 63-year-old patient, known to have suffered from lymphogranulomatosis X for 4 years is reported, in whom a cutaneous cryptococcosis appeared as first sign of a disseminated cryptococcosis . Despite systemic therapy with amphotericin B, the patient died after a period of 2 months . Differential diagnosis of skin tumours of immunosuppressed patients includes rare skin mycoses, and both histological and mycological examinations should be performed.

Pathology, 1991 Jul, 23(3), 256 - 8
Cryptococcal epididymo-orchitis complicating steroid therapy for relapsing polychondritis; James CL et al.; Disseminated cryptococcosis is a known complication of steroid therapy . Infection within the genito-urinary tract is usually assumed to be part of generalized cryptococcosis complicating a primary pulmonary focus . A case of isolated testicular cryptococcal orchitis complicating steroid therapy for relapsing polychondritis is presented . To the authors' knowledge isolated cryptococcal orchitis has not been previously described.

J Exp Med, 1991 Jul 1, 174(1), 151 - 60
The mouse antibody response to infection with Cryptococcus neoformans: VH and VL usage in polysaccharide binding antibodies; Casadevall A et al.; Cryptococcus neoformans is a ubiquitous fungus that can cause serious infections in humans . The fungus has a polysaccharide (C . neoformans capsular polysaccharide; CNPS) capsule that contributes to its pathogenicity and can elicit an antibody response . Nevertheless, only 4 of 60 BALB/c mice chronically infected with C . neoformans had a detectable increase in serum anti-CNPS . The sera of three responder mice contained both IgM and IgG anti-CNPS antibody, and the titers of lambda and kappa anti-CNPS antibody were approximately equal . Eight IgM and one IgG3 monoclonal antibodies (mAbs) were generated from the spleen of one responder mouse, and one IgA was generated from the spleen of another mouse . Seven of the IgMs, the IgG3, and the IgA mAb had lambda light chains and were specific for serotype D CNPS . Molecular analysis confirmed that this was a highly restricted antibody response . All of the D-specific antibodies used VH441, JH3, and either V lambda 2/J lambda 2 or V lambda 1/J lambda 1, and all had the same heavy chain CDR3 amino acid sequence, even though there were differences in the nucleotide sequence of the N/D segment . One IgM mAb reacted with both serotype A and D CNPS, and this mAb used different VH and JH genetic elements and had kappa light chains . All the anti-CNPS mAbs used J proximal VH gene elements that have previously been shown to bind dextran and other polysaccharides . Sequence and Southern blot analysis indicate that the serotype-D CNPS-specific mAbs arose from only a few precursor B cells.

Neurology, 1991 Jun, 41(6), 841 - 5
Neuro-ophthalmologic signs of AIDS: 50 patients; Keane JR; In 50 hospitalized patients with acquired immunodeficiency syndrome, signs of central eye movement limitation (28 cases) were most common . Peripheral eye movement limitations (18), abnormalities of vision (18), and abnormal spontaneous eye movements (15) occurred with about equal frequency . Meningitis (17), usually due to lymphoma (8) or Cryptococcus (8), was the usual cause of peripheral nervous system involvement, while toxoplasmosis (18) was more common than lymphoma (4) or presumed viral causes (8) in producing CNS dysfunction . The midbrain and pretectal (8) were affected about as often as the pontine tegmentum (9), but rostral brainstem lesions appeared to be the result of toxoplasmosis (4) or lymphoma (3), whereas a viral etiology was the presumed cause of most caudal stem involvement.

Arch Intern Med, 1991 Jun, 151(6), 1205 - 14
Extrapulmonary Pneumocystis carinii infections in the acquired immunodeficiency syndrome; Cohen OJ et al.; Pneumocystis carinii is a frequent cause of interstitial pneumonitis in patients with cell-mediated immunodeficiencies . Extrapulmonary P carinii infection is a rare manifestation of disease caused by this organism . Nevertheless, reports of extrapulmonary P carinii infection are increasing in the setting of the acquired immunodeficiency syndrome (AIDS) . We report two cases of extrapulmonary P carinii infection in patients with AIDS and review the literature on this subject . We identified 37 such cases: in 19 cases, P carinii pneumonia was present concurrently; in 18 cases, involvement was exclusively extrapulmonary . A minority of patients were receiving aerosolized pentamidine isethionate therapy . Most patients had a history of P carinii pneumonia, and other AIDS-related illnesses, such as cytomegalovirus infection, mycobacterial disease, candidiasis, Kaposi's sarcoma, and cryptococcosis were common . Concurrent cytomegalovirus infection indicated a poor prognosis, while otic pneumocytosis was associated with a favorable outcome . Pathologic evidence suggested that extrapulmonary pneumocystosis occurred by hematogenous and lymphatic dissemination from the lungs in most cases . In other cases, extrapulmonary pneumocystosis appeared to be due either to reactivation of latent infection in extrapulmonary sites or to primary infection of these sites . Further studies are needed to determine the true frequency of extrapulmonary involvement in P carinii infections and to define risk factors for acquisition of extrapulmonary pneumocytosis.

Infect Immun, 1991 Jun, 59(6), 2140 - 6
Susceptibility of beige mutant mice to candidiasis may be linked to a defect in granulocyte production by bone marrow stem cells; Ashman RB et al.; The beige mutation in mice has a pervasive effect on mechanisms of host resistance to infectious agents . Best characterized are defects in granulocyte chemotaxis and phagocytosis, which are associated with increased susceptibility to bacteria, and a deficiency in the levels of natural killer (NK) cells, which has been linked to decreased resistance to both murine cytomegalovirus and the yeast Cryptococcus neoformans . The objective of the present experiments was to explore the cellular basis of the enhanced susceptibility of beige mice to systemic infection with the yeast Candida albicans . In contrast to murine cytomegalovirus and C . neoformans, infection with C . albicans did not induce any detectable NK cell activity in the spleen of bg/bg or bg/+ mice . Unfractionated bone marrow (BM) displayed some candidacidal activity, mediated by both phagocytic and nonphagocytic cells; however, there was no difference between homozygous and heterozygous mice in the effector function of normal BM cells or mononuclear cells derived from either short- or long-term BM cultures . On the other hand, peritoneal granulocytes from bg/bg mice were significantly more effective than those from bg/+ mice in killing Candida blastoconidia in vitro . A similar comparison of granulocytes from short-term BM cultures showed that the activities of cells from bg/bg and bg/+ mice were equivalent, indicating that the granulocytes derived from the peritoneal cavity of bg/bg mice had probably been exposed to some form of nonspecific stimulation in vivo . Somewhat surprisingly, long-term BM cultures did not support the continual growth of bg/bg granulocytes, and it is possible that the beige mutation may be associated with a lesion in the differentiation pathway that leads to the production of granulocytes . Taken together, the data indicate that, in beige mice, granulocytes rather than NK cells are a major determinant of natural resistance to C . albicans infections.

J Leukoc Biol, 1991 Jun, 49(6), 533 - 41
Inflammatory responses to cryptococcosis in congenitally athymic mice; Salkowski CA et al.; Histopathology revealed that nu/nu mice developed both acute and chronic inflammatory responses following infection with Cryptococcus neoformans . In comparison to inflammatory responses in nu/+ mice, the responses in nu/nu mice were delayed, less intense, contained predominantly more polymorphonuclear leukocytes (PMNs) than macrophages (M phi s), and did not develop into granulomas . In addition, nu/nu mice developed cryptococcal skin lesions demonstrating that C . neoformans is dermatotropic in a T-cell deficient host . Quantitative culturing of infected organs confirmed that delayed and incomplete inflammatory responses observed in nu/nu mice correlated with their enhanced susceptibility to C . neoformans.

Rinsho Shinkeigaku, 1991 Jun, 31(6), 658 - 61
{A case of acute cerebellar encephalitis due to Cryptococcus neoformans}; Watanabe Y et al.; A case of acute cryptococcal cerebellar encephalitis with CT enhancement confined to the cerebellum is reported . A 46-year-old man with hepatoma was admitted with chief complaints of headache, fever and dizziness . On admission, cerebellar signs (disturbance of finger-to-nose test and of heel-to-knee test, intention tremor, and truncal ataxia) were neurologically noted . However, there were no brainstem signs . Head CT showed swelling and enhancement of the cerebellar cortex and dilatation of the cerebral ventriculi . Cryptococcus neoformans was detected in a culture of the patient's CSF . Clinical symptoms and signs, and enhancement of the cerebellum on CT gradually diminished after administration of anti-fungal drugs, and CSF became negative for cryptococcal antigen 6 months after admission.

Acta Ophthalmol (Copenh), 1991 Jun, 69(3), 402 - 5
Retinitis following disseminated cryptococcosis in a renal allograft recipient . Efficacy of oral fluconazole; Agarwal A et al.; A case of retinitis following disseminated cryptococcus neoformans infection in a renal allograft recipient is reported . Therapy with oral fluconazole showed a remarkable improvement at the end of 8 weeks . This is the first report of the use of fluconazole in the treatment of cryptococcal retinitis.

J Cutan Pathol, 1991 Jun, 18(3), 204 - 9
Reactivity of fungal organisms in tissue sections using anti-mycobacteria antibodies; Wiley EL et al.; Sixty-four cases of deep fungal infections diagnosed using PAS or silver stains and 18 control cases of sarcoidosis, M . tuberculosis and M . leprae infection were stained using commercial polyclonal antibody raised against M . paratuberculosis (MP), M . Duvalii (MD), and Bacillus Calmette-Guerin (BCG) . Nine of 13 cases of sporotrichosis stained positively using anti-MP antibody only; 13 of 14 cases of histoplasmosis stained with anti-BCG, anti-MD, and anti-MP; seven cases of cryptococcosis had only focal staining of rare individual organisms within masses of negative organisms; seven of eight cases of coccidioidomycosis stained predominantly with anti-BCG and anti-MP; eight cases of aspergillus had focal (1 to 5% of organisms) staining of hyphae with anti-BCG and anti-MD; and four of 12 cases of Candida infection showed focal nonspecific staining with both antibodies and nonimmune serum . Control cases of sarcoidosis exhibited no staining with any of the three antibodies, whereas cases of mycobacterial infection showed staining of bacilli and intracellular debris with all three antibodies.

Mycopathologia, 1991 Jun, 114(3), 153 - 7
Overview: cryptococcosis in the patient with AIDS; Sugar AM; Cryptococcosis is currently the most common life threatening mycoses found in patients with the acquired immunodeficiency syndrome (AIDS) . Extrapulmonary involvement is most frequently seen, especially in the central nervous system and skin . Clinical findings are non-specific, even in patients with meningitis . Threshold for diagnosis of this infection should be low, with serum cryptococcal antigens, blood, urine and sputum cultures for Cryptococcus neoformans performed in febrile AIDS patients . Lumbar puncture should also be performed if unexplained headaches are included in a patient's complaints . There is currently no consensus for the most appropriate treatment strategy and the role of oral azoles versus amphotericin B or amphotericin B with flucytosine remains a serious question in need of further controlled studies . Patients eligible for multicentered trials should be encouraged to participate . Therapy for others should be individualized . This review will address some of these issues.

J Clin Microbiol, 1991 Jun, 29(6), 1260 - 1
False-positive reactions in the latex agglutination test for Cryptococcus neoformans antigen; Heelan JS et al.; The latex agglutination test for Cryptococcus neoformans antigen is a simple and rapid procedure for the diagnosis of cryptococcal meningitis . Although the test is sensitive, care must be taken to prevent contamination of the sample, which may result in false-positive reactions . It was discovered in our laboratory that immersion of a platinum wire inoculating loop into a sample of cerebrospinal fluid prior to testing introduced interfering substances leading to nonspecific agglutination . After further studies, it was determined that trace amounts of surface condensation (syneresis fluid) from agar, either added to the cerebrospinal fluid or adhering to the loop, were the probable source of contamination . It is suggested that the latex agglutination test for C . neoformans antigen be performed prior to culture or on a separate sample.

J Clin Neuroophthalmol, 1991 Jun, 11(2), 96 - 103
Cryptococcal optic neuropathy in the acquired immune deficiency syndrome; Golnik KC et al.; Cryptococcus neoformans infection occurs frequently in patients with the acquired immune deficiency syndrome (AIDS) . Cryptococcal meningitis can result in optic neuropathy . Improvement in afferent visual system dysfunction has not been documented . We report three patients with AIDS who developed either unilateral (1) or bilateral (2) afferent visual system dysfunction . The bilaterally affected patients had visual field deficits compatible with chiasmal involvement . All patients had improvement in their vision following appropriate treatment with amphotericin B . Reactivation of cryptococcal infection was heralded by neuro-ophthalmic manifestations in two patients, in spite of maintenance therapy . Despite the poor overall prognosis, AIDS patients with presumed cryptococcal optic neuropathy can benefit from optimal therapy.

Mycopathologia, 1991 Jun, 114(3), 179 - 86
Immunosuppression in experimental cryptococcosis in rats . Induction of efferent T suppressor cells to a non-related antigen; Masih DT et al.; Using a rat model, we have previously demonstrated that infection with Cryptococcus neoformans can trigger the production of a series of suppressor cells that specifically inhibit the cell-mediated immune response to a non-related antigen, human serum albumin (HSA), that has been injected 7 days after the infection . We previously determined that the cryptococcal infection induces afferent suppressor or suppressor induction cells (Ts1) to HSA . The primary objective of the present study was to investigate the suppressor cells involved in the efferent phase of delayed-type hypersensitivity (DTH) response to HSA in rats infected with C . neoformans and immunized with the non-related antigen and determine the role that the Ts1 cell plays in the induction of that cell . For this purpose, the spleen mononuclear (SpM) cells containing the Ts1 or SpM cells from immunized non-infected rats (used as donor controls) were transferred to two groups of syngeneic naive recipients (first recipients) . Later, the SpM cells from both groups of animals were transferred to rats immunized with HSA (second recipients) . The efferent limb of the DTH response to HSA was suppressed in the recipients that received SpM cells from donors injected with Ts1 cells . Additional HSA antigen was not required for induction of these efferent suppressor cells . Furthermore, we here show that these cells are resistant to treatment with cyclophosphamide (Cy), and that they can activate another suppressor population . The latter are Cy sensitive and are present in the immune recipient.

Arq Neuropsiquiatr, 1991 Jun, 49(2), 208 - 10
Ketoconazole in the treatment of cryptococcosis of the central nervous system; Trevisol-Bittencourt PC et al.; Two patients with cryptococcosis of the CNS were treated with ketoconazole (KTZ), an imidazole derivative with fungistatic properties: they had either failed standard therapy (Amphotericin-B + 5-Fluorocytosine) or suffered intolerable side-effects to it . Both patients were administered KTZ 800 mg/day as monotherapy for six months without interruption and both responded . One month after KTZ therapy was withdrawn, however, a relapse of the infection was seen in one case . Side-effects were minimal during the trial of treatment . KTZ could be a useful drug in some cases of neurocryptococcosis.

Arq Neuropsiquiatr, 1991 Jun, 49(2), 159 - 63
{Neurological complications in acquired immunodeficiency syndrome: experience at the Hospital Universitario Clementino Fraga Filho-Universidade Federal do Rio de Janeiro}; Puccioni-Sohler M et al.; The frequency of neurological manifestations was evaluated in 653 HIV infected patients admitted in a university hospital in Rio de Janeiro city, Brazil, in the 1985-1989 period . A total of 172 (26%) patients developed neurological symptoms . Central nervous system complications included: cerebral toxoplasmosis (80), cryptococcal meningitis (57), subacute encephalitis (17), tuberculosis (8) and aseptic meningitis (2), progressive multifocal leukoencephalopathy (2) and vacuolar myelopathy (6) . Peripheral neuropathy occurred in three cases . The clinical and tomographic aspects were analysed . The majority of the patients died within six months after the onset of the neurological disease.

J Chemother, 1991 Jun, 3(3), 139 - 42
Fluconazole, itraconazole and ketoconazole in-vitro activity . A comparative study; Arzeni D et al.; We compared in-vitro activity of fluconazole, itraconazole and ketoconazole by evaluating their Minimal Inhibitory Concentrations (MICs) for 100 fungal strains isolated from different biological specimens of ARC/AIDS patients . A semisolid agar medium was used: this method is suitable for testing molds and yeasts, and can be applied to all azole antifungal drugs . Fluconazole had higher MICs than two other tested drugs, especially for Candida krusei strains; however it never had a MIC higher than 40 mg/l . Itraconazole and ketoconazole had MICs higher than 40mg/l for one Cryptococcus neoformans strain . There were no significant differences for itraconazole and ketoconazole among the tested strains.

J Clin Microbiol, 1991 May, 29(5), 980 - 4
Production of species-specific murine monoclonal antibodies against Cryptococcus neoformans which recognize a noncapsular exoantigen; Hamilton AJ et al.; Three monoclonal antibodies (MAbs), designated 7C5, 7C9, and 5G8, against a cytoplasmic antigen of Cryptococcus neoformans were produced . MAbs 7C5 and 7C9 recognize culture filtrate antigen (exoantigen) of both encapsulated and nonencapsulated isolates of this pathogen, which suggests that they do not recognize capsular polysaccharide material . This is supported by immunofluorescence data which show reactivity of all 3 MAbs to cytoplasm and cell membranes only . MAb 7C9 also recognized C . neoformans var . gattii antigens but no other fungal pathogens tested in an enzyme-linked immunosorbent assay, while 7C5 and 5G8 recognized antigens of the cross-reactive pathogen Trichosporon beigelii but did not recognize either C . neoformans var . gattii isolates or any other fungal antigens . By Western blot (immunoblot), 7C9 detected antigen at 110 to 120, 65 to 70, 45 to 50, and 36 to 38 kDa; in addition to the latter band, the other two MAbs recognized a band at approximately 30 kDa . All three MAbs were of the immunoglobulin G1 subclass . The two MAbs which are capable of reacting with noncapsular culture supernatant antigen have possible uses in serodiagnosis, particularly in AIDS patients infected with C . neoformans, since in this group the present latex agglutination test has some limitations.

Am J Med Sci, 1991 May, 301(5), 329 - 30
Cryptococcal pleural effusion preceding cryptococcal meningitis in AIDS; Grum EE et al.; The authors report a case in which a small cryptococcal pleural effusion preceded the development of severe cryptococcal meningitis in an HIV-positive patient . The appearance of an isolated transient pleural effusion is a very unusual presentation for AIDS-related complications . The authors suggest that cryptococcal infection be considered in this setting.

J Infect Dis, 1991 May, 163(5), 1114 - 20
Improved amphotericin B activity by a monoclonal anti-Cryptococcus neoformans antibody: study during murine cryptococcosis and mechanisms of action; Dromer F et al.; Current therapy of cryptococcosis is unsatisfactory, particularly in patients with AIDS . Experimental cryptococcosis models in DBA/2 mice were used to determine whether the murine monoclonal anticryptococcal antibody (designated E1) might potentiate the chemotherapeutic effect of amphotericin B (AmB) . According to the inoculum size, these mice died spontaneously from acute pneumonia (high inoculum) or from brain swelling (lower inoculum) . AmB and E1 together significantly improved the survival of mice in both models compared with AmB alone . The mechanisms by which E1 might potentiate AmB activity were investigated in vitro . When cryptococci were preincubated with AmB or another polyene antibiotic, nystatin, there was an augmented binding of E1 . AmB enhanced phagocytosis by unstimulated peritoneal macrophages in the presence of E1 or normal rabbit immunoglobulins . Normal and immune IgG deserve further study to determine under what circumstances the chemotherapeutic effect of AmB can be enhanced.

J Infect Dis, 1991 May, 163(5), 1108 - 13
Killing of Cryptococcus neoformans by human peripheral blood mononuclear cells stimulated in culture; Levitz SM et al.; Since cell-mediated immunity (CMI) is critical for host defenses against the encapsulated fungus Cryptococcus neoformans, the production of human antifungal effector cells as a consequence of the CMI response was investigated . Peripheral blood mononuclear cells (PBMC) were stimulated in culture with killed C . neoformans . Stimulated (but not unstimulated) PBMC killed a subsequent inoculum of live encapsulated organisms, with maximal killing seen after 3-7 days . Killing required the presence of both adherent and nonadherent stimulated PBMC and was enhanced by anticapsular antibody . In contrast, unstimulated PBMC and the adherent fraction of stimulated PBMC killed an isogenic acapsular strain of C . neoformans . These data suggest that the CMI response controls cryptococcosis by eliciting two populations of fungicidal cells acting synergistically . Moreover, capsule, by thwarting the ability of unstimulated PBMC to kill C . neoformans, seems to obligate the host to mount an immune response to generate fungicidal cells.

AJR Am J Roentgenol, 1991 May, 156(5), 921 - 4
Prevalence of air bronchograms in small peripheral carcinomas of the lung on thin-section CT: comparison with benign tumors; Kuriyama K et al.; Despite improved techniques--such as bronchoscopy and percutaneous needle biopsy--to evaluate pulmonary nodules, there are still many cases in which surgical resection is necessary before carcinoma can be differentiated from benign lesions . The present study was undertaken to determine if the presence of an air bronchogram or air bronchiologram (patent visible bronchus or bronchiole) is useful in distinguishing small lung cancers from benign nodules . Thin-section chest CT scans were obtained in patients with 20 peripheral lung cancers less than 2 cm in diameter (18 adenocarcinomas, one squamous cell carcinoma, and one large cell carcinoma) and 20 small benign nodules (eight hamartomas, seven tuberculomas, two foci of aspergillosis, one focus of cryptococcosis, one chronic focal interstitial pneumonitis, and one plasma cell granuloma) . The images were compared with regard to the patency of any bronchus or bronchiole within the lesions . After surgical resection, the specimens were inflated with agar and sectioned transversely to correlate gross morphology and low-power histologic sections with the CT appearance . An air bronchogram or air bronchiologram was seen in the tumors on 65% of CT scans and 70% of histologic sections . Benign nodules had a patent bronchus or bronchiole on CT scans and histologic sections in only one case (5%) . These findings suggest that the presence of an air bronchogram in a lung nodule is a useful finding to help differentiate adenocarcinomas from benign lesions.

Vestn Rentgenol Radiol, 1991 May-Jun, (3), 34 - 9
{X-ray pulmonary manifestations in patients infected with the human immunodeficiency virus}; Meleshenkov BA et al.; PIP: The acquired immunodeficiency syndrome (AIDS) was first diagnosed in burundi in 1983 when a large number of patients were registered with Kaposi's sarcoma, cryptococcal meningitis, and disseminated candidiasis . In the 1st phase of the disease the vi rus is dormant . In the 2nd phase seroconversion appears; and in the 3rd phase generalized adenopathy emerges . In the 4th phase the full-blown disease appears as a result of cellular immunity deficit with emaciation, fever, sweating, chronic diarrhea, asthenia, blood parameter changes (lymphopenia, thrombocytopenia, leukopenia, anemia, and specific immune disorders) . The early phases can be diagnosed by serological tests . During 1989 a group of 155 patients with 1st signs of seropositivity were studied in the central hospital of Bugumbura . The available clinical diagnostic markers were: 56 cases of herpes, 26 cases of generalized adenopathy, 25 cases of inflammatory infiltration of paraganglionic zones, 13 abscesses and phlegmons, 8 cases of chronic proctitis, 8 prurigo cases, 7 cases of chronic pneumonia and bronchitis, 4 cases of paresis of the facial nerve, 4 cases of Kaposi's sarcoma, 2 cases of fresh syphilis, 2 cases of anemia, asthenia, dizziness, and weight loss . Tomo- and zonographical X-ray study of the thorax of 80 patients aged 20-65 (51 men and 29 women) was performed . In 62 patients changes in the lungs were evident . In 2 patients tuberculosis of the lungs was diagnosed: miliary TB in a 26-year woman and disseminated TB in a 31-year man . 2 chronic and 3 bronchial, and 10 interstitial pneumonia cases were diagnosed in 15 patients with average age of 30 years . 4 patients had peribronchial and pneumonic infiltrations . In a group of 45 patients magnified picture showed no deformation in the lungs; and only 5 had respiratory organ pathology . Interstitial pneumonia was the most often diagnosed ailment by X-ray inpatients infected with HIV .

AIDS, 1991 May, 5(5), 583 - 6
HIV-1 seropositivity and mortality at University Hospital, Kinshasa, Zaire, 1987; Nelson AM et al.; This study examines the impact of HIV-1 infection and AIDS on 500 of 563 consecutive deaths at University Hospital, Kinshasa, Zaire, in late 1987 . HIV-1 seroprevalence was 31% for the entire population and 43% for the 247 adults . Forty-two (38%) of the 110 HIV-1-seropositive adult deaths occurred in those between the ages of 25 and 34 years . The mean age of death for seropositives was 36 years, 7.5 years less than seronegative deaths . AIDS and AIDS-associated diagnoses such as cryptococcal meningitis, chronic diarrhea and pneumonia accounted for 42% of all adult deaths and 74% of all HIV-1-seropositive adult deaths . Seventeen per cent of 50 sera initially negative by enzyme-linked immunosorbent assay (ELISA) were ultimately found to be HIV-1-seropositive by Western blot or p24 antigen testing . The data indicate that HIV-1 infection and AIDS contribute significantly to adult mortality in Kinshasa population and that sensitivity of ELISA tests decreases in terminal HIV-1 infection.

Jpn J Antibiot, 1991 May, 44(5), 552 - 61
{In vivo and in vitro antifungal activity of fluconazole}; Kawasaki K et al.; We examined in vivo efficacy and in vitro activity of fluconazole, a novel triazole antifungal agent, and obtained results which are summarized as follows: 1 . Fluconazole showed a higher serum concentration than ketoconazole after oral administration to mice . The 50% effective dose of fluconazole administered orally to mice was similar to that of fluconazole injected to mice intraperitoneally in a systemic candidiasis model . 2 . Prophylactic effects of fluconazole were excellent against systemic candidiasis, cryptococcosis and aspergillosis in mice in comparison with those of ketoconazole and miconazole . 3 . The multiple administration of fluconazole effectively decreased the number of viable cells of Candida albicans colonized in kidneys of mice when the serum level of fluconazole was kept to exceed its IC99 values against the inoculated pathogen . Thus, a good correlation between the in vitro activity of fluconazole and its in vivo efficacy was confirmed . In vivo efficacies of ketoconazole and miconazole, however, failed to reflect their marked in vitro activities . 4 . C . albicans No . 32 developed no drug-resistance to fluconazole during transfers in medium containing fluonazole at a concentration of 1 micrograms/ml.

Rev Infect Dis, 1991 May-Jun, 13(3), 480 - 6
The growing problem of mycoses in patients infected with the human immunodeficiency virus; Diamond RD; With the rapid increase in cases of AIDS over the past 10 years, certain mycoses have dramatically risen in frequency, particularly those contained by T cell-mediated mechanisms of host defense . In this clinical setting mucocutaneous candidiasis as well as systemic cryptococcosis, histoplasmosis, and coccidioidomycosis pose special diagnostic and/or therapeutic challenges . Compared with fungal infections in general, AIDS-associated mycoses are more likely to have nonspecific clinical manifestations; moreover, treatments effective in other settings seldom are curative . These problems have led to new vigilance regarding mycoses in the differential diagnosis of complications of infection due to the human immunodeficiency virus (HIV) and have necessitated a redefinition of goals: the aim is now to suppress rather than cure infection in most cases . This change has stimulated trials of new antifungal agents and regimens particularly designed to facilitate long-term outpatient management of mycoses without interfering with treatment of either HIV infection itself or other concomitant complications.

Infect Immun, 1991 May, 59(5), 1785 - 9
Cutaneous cryptococcosis in athymic and beige-athymic mice; Salkowski CA et al.; The dermotropism of Cryptococcus neoformans SLHA in congenitally athymic (nu/nu) and doubly immunodeficient beige-athymic (bg/bg-nu/nu) mice is described . Both bg/bg-nu/nu and nu/nu mice developed cutaneous cryptococcosis within 7 to 12 days following intravenous challenge with 10(4) encapsulated yeast cells . Macroscopically, cutaneous lesions appeared as small subcutaneous nodules without ulceration . Cryptococcal skin lesions were observed primarily on the flank of nu/nu mice, whereas skin lesions in bg/bg-nu/nu mice were distributed over the trunk, abdomen, and face . While bg/bg-nu/nu mice had four times as many macroscopic skin lesions as nu/nu mice on day 14 after intravenous challenge, the skin lesions in nu/nu mice were larger . Histopathology revealed large foci of encapsulated yeasts extending from the basement membrane of the epidermis through the dermis to the underlying musculature . Yeasts in these lesions evoked a minimal inflammatory response that consisted primarily of macrophages . Interestingly, yeast cells appeared to be degrading collagen bundles located in the dermis . The dermotropic strain used in this study produced gelatinase and other proteases in vitro . These results indicate that C . neoformans can be dermotropic in a T-cell-deficient host and that proteases may be a virulence factor(s).

Riv Eur Sci Med Farmacol, 1991 May-Aug, 13(3-4), 173 - 7
{Clinical description of three cases of cerebral cryptococcosis in patients with AIDS treated with fluconazole}; Izzo E et al.; The authors have evaluated the efficacy of Fluconazole (400 mg/iv/die for three days and after 200 mg/iv/die for 18 days) in three AIDS and SNC Cryptococcal infection patients . Two patients have shown healing of meningeal syndrome and negative isolation after 21 days of therapy; one patient, however, died because of Cytomegalovirus pneumonia . It is of note that early spinal puncture in AIDS patients with neurological symptoms enables an early diagnosis and immediate therapy . Fluconazole treatment has been well tolerated and immediately effective to resolve two of the cases observed; the oral prophylaxis with 100 mg/die of Fluconazole after 6 months has been effective to prevent the relapses of the disease.

Mycoses, 1991 May-Jun, 34(5-6), 205 - 15
Protective effect of human granulocyte colony-stimulating factor (hG-CSF) on Cryptococcus and Aspergillus infections in normal and immunosuppressed mice; Polak-Wyss A; Prophylactic treatment with human granulocyte colony-stimulating factor (hG-CSF) affords significant protection against systemic aspergillosis or pulmonary aspergillosis in neutropenic (cyclophosphamide-treated) mice but not in cortisone-treated animals . Cryptococcosis does not respond to hG-CSF therapy . Our data show that granulocytes play an important role in the immune defense against aspergillosis, but not against cryptococcosis . Combined treatment using hG-CSF and conventional antimycotics shows a significant beneficial effect in systemic or pulmonary aspergillosis.

Infect Immun, 1991 May, 59(5), 1747 - 54
Murine natural killer cells are fungicidal to Cryptococcus neoformans; Hidore MR et al.; Murine natural killer (NK) cells have been shown to bind to and inhibit the growth of Cryptococcus neoformans in vitro and to contribute to clearance of the organism in vivo . However, it is unclear whether NK cells actually kill cryptococci or simply inhibit proliferation of the fungal target . Therefore, the studies presented here were designed to determine whether NK cells are fungicidal to C . neoformans targets . C . neoformans viability was determined on the basis of the metabolic function of two different enzyme systems, as measured by the two vital stains MTT {3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide} and fluorescein diacetate . Cryptococcal viability, as determined by vital stains, was compared with cryptococcal proliferation, as measured by microcolony formation in agarose at the individual cell level and by CFU counts or extinction dilution analysis in the total cell suspension . Initial comparisons of the vital stains and proliferation assays indicated that these methods effectively distinguished between live and heat-killed cryptococci at the individual cell level and in the total cell suspensions . After cryptococci were incubated with murine NK cells for 18 h, vital stains demonstrated that at the single conjugate level and in the total cell suspension, NK cells kill bound C . neoformans target cells . In addition, the numbers of dead cryptococci in the NK cell-C . neoformans suspensions as determined by the vital stains were comparable to the numbers of cryptococci that were unable to proliferate . Kinetics of NK cell-mediated C . neoformans binding and killing at the single conjugate level and in the total cell suspension were assessed by MTT staining at 2-h intervals after mixing effector and target cells, and the data support the concept that NK cell-C . neoformans binding precedes cryptococcal death . Furthermore, unbound, dead fungal cells were observed in the NK cell-C . neoformans suspensions after 18 h, suggesting that NK cell-C . neoformans interactions may involve both effector cell recycling and killing of unbound cryptococci by soluble cytotoxic factors . In conclusion, the results of these studies firmly establish that NK cells kill C . neoformans.

Histopathology, 1991 May, 18(5), 459 - 64
Surgical pathology of the liver in HIV infection; Wilkins MJ et al.; In the 6-year period 1984-1989, 101 liver biopsies or 'needle necropsies' from human immunodeficiency virus positive patients were examined histologically . Of these, only nine showed no abnormality whatsoever . The commonest histological findings were either fatty change or changes related to co-existent chronic viral hepatitis . Granulomas were seen in 15 cases, four of which were positive for acid-fast bacilli . A range of organisms were recorded: cytomegalovirus (4); Histoplasma capsulatum (1); Pneumocystis carinii (2); Cryptococcus neoformans (1); and Leishmania donovani (1) . There were two cases of non-Hodgkin's lymphoma, but no cases of Kaposi's sarcoma . Marked iron deposition, which correlated with multiple blood transfusions was seen in nine biopsies . We were unable to identify any histological feature in the liver as being specific for HIV infection . The high incidence of liver abnormalities reflects: (i) the coincident exposure to hepatotropic viruses; (ii) the presence of opportunistic infections and neoplasms, usually part of a disseminated multi-organ process arising in the setting of profound immune depression; (iii) iatrogenic causes, in particular iron overload related to multiple blood transfusions received for treatment of zidovudine-induced anaemia; and (iv) non-specific changes associated with chronic debilitating disease.

Jpn J Antibiot, 1991 May, 44(5), 588 - 99
{The therapeutic effects of itraconazole, a new triazole antifungal agent, for experimental fungal infections}; Uchida K et al.; The therapeutic efficacy of itraconazole (ITZ), and oral triazole antifungal agent, was studied using several experimental fungal infections in animals . The following results were obtained: 1 . ED50 values of ITZ and ketoconazole (KCZ) in a murine model of systemic candidiasis produced by intravenous challenge of Candida albicans alls were 32.9 mg/kg and 224 mg/kg, respectively . ITZ suppressed the proliferation of Candida experimentally colonized in the GI-tract of mice and/or a secondary dissemination induced by prednisolone . 2 . An oral dose of 40 mg/kg/day ITZ administered for experimental pulmonary cryptococcosis in mice inhibited the fungal proliferation in the lung and the dissemination to the brain . 3 . ED50 values of ITZ and KCZ for experimental systemic Aspergillus infection in mice were 103.6 mg/kg and 882 mg/kg, respectively . 4 . ITZ suppressed the development of local symptoms in guinea pigs with experimental dermatophytosis . Culture studies performed on cutaneous tissues from infected sites on day-19 postinfection revealed that ITZ treatment lowered the culture-positive rate to a greater extent than KCZ-treatment . 5 . Plasma concentrations of ITZ after a single dose of 100 mg/kg in mice were determined using the bioassay method: Cmax was 11 micrograms/ml and T 1/2 was 24 hours . 6 . These results show that oral ITZ is highly effective in the treatment of deep-seated and superficial fungal infections produced in experimental animals.

Jpn J Antibiot, 1991 May, 44(5), 562 - 70
{In vitro antifungal activity of itraconazole, a new triazole antifungal agent, against clinical isolates from patients with systemic mycoses}; Uchida K et al.; The in vitro antifungal activity of itraconazole (ITZ), a new oral triazole antifungal agent, against clinical isolates from patients with systemic mycoses were compared with those of existing systemic antifungals, viz . ketoconazole (KCZ), miconazole or amphotericin B . The studies were performed with 65 isolates of pathogenic yeasts and 13 isolates of Aspergillus spp . using the agar dilution method on casitone agar . ITZ showed the most potent antifungal activities against isolates of pathogenic yeasts including several Candida spp . (Candida parapsilosis, Candida krusei, Candida guilliermondii), Cryptococcus neoformans, Trichosporon cutaneum (MIC less than or equal to 0.08 micrograms/ml) and Aspergillus spp . including Aspergillus fumigatus (MIC less than or equal to 5 micrograms/ml) . On the other hand, activities of ITZ against isolates of other Candida spp . such as Candida albicans and Candida glabrata were lower than those of KCZ and other reference drugs . Some isolates of C . albicans and C . tropicalis were not completely inhibited by ITZ even at concentrations above 10 micrograms/ml on casitone agar . However, in the micro-broth dilution method using synthetic amino acid medium, fungal as the test medium, ITZ completely inhibited the growth of all these isolates at drug concentrations of less than or equal to 0.20 micrograms/ml.

Pharm Weekbl Sci, 1991 Apr 26, 13(2), 45 - 57
Fluconazole . Review and situation among antifungal drugs in the treatment of opportunistic mycoses of human immuno-deficiency virus infections; Vincent-Ballereau FN et al.; Fluconazole is a novel triazole antifungal drug chiefly used in the treatment of opportunistic mycoses in immuno-compromised patients, particularly those with the acquired immuno-deficiency syndrome (AIDS) . In comparison with other antifungal drugs, fluconazole has outstanding physical and pharmacokinetic properties, such as an excellent aqueous solubility allowing a parenteral formulation, high bioavailability by the oral route, even distribution throughout the tissues, including the central nervous system and the cerebro-spinal fluid, a long half-life (permitting once daily administration), and low binding to plasma proteins . It is excreted mainly as unchanged drug in the urine . Fluconazole is a broad-spectrum antifungal agent, especially effective against Candida spp., Cryptococcus neoformans and dermatophytes . Its antifungal efficacy was mainly proved by testing in animal models, since there is no relationship between in vitro and in vivo activities . It possesses a low toxicity and it is well-tolerated . Fluconazole is currently marketed for the treatment of oropharyngeal candidiasis in immuno-compromised patients and of atrophic oral candidiasis . Its place in the treatment of opportunistic mycoses in human immuno-deficiency virus-positive patients, in particular cryptococcal meningitis, is still under investigation but is promising.

Carbohydr Res, 1991 Apr 2, 211(1), 103 - 16
Glucuronoxylomannan of Cryptococcus neoformans serotype B: structural analysis by gas-liquid chromatography-mass spectrometry and 13C-nuclear magnetic resonance spectroscopy; Turner SH et al.; The major extracellular polysaccharide (glucuronoxylomannan, GXM) from six strains of Cryptococcus neoformans serotype B was characterized by gas-liquid chromatography (g.l.c.), g.l.c.-mass spectrometry (g.l.c.-m.s.), and nuclear magnetic resonance (n.m.r.) spectroscopy . Ultrasonic irradiation (u.i.) was used to reduce the mol.wt . of native GXM from 9.75 x 10(5) to 1.15 x 10(5) without apparent change in its composition (GXM-S) . The Xylp:Manp:GlcpA molar ratio of the GXM and GXM-S from the six strains of C . neoformans serotype B is approximately 3.5:3.0:0.6 . GXM-S was O-deacetylated (GXM-D) by treatment with NH4OH . The 13C-n.m.r . analysis of GXM-D gave spectra that served as characteristic fingerprints of the structure and also facilitated the assignment of the anomeric carbon resonances to specific structural moieties present in GXM-D . The GXM-D from each serotype B strain was found to be similar by 13C-n.m.r . spectroscopy . The structure contains a linear (1----3)-alpha-D-Manp backbone substituted with 2-O-beta-GlcpA and 2-O-beta-Xylp . beta-Xylp is also O-4 linked to the Manp substituted with GlcpA . In addition, a model for the disposition of the Xylp and GlcpA side chain substituents along the mannopyranan backbone is proposed, based upon results from the combination of g.l.c.-m.s . and 13C-n.m.r . spectroscopy.

Kansenshogaku Zasshi, 1991 Apr, 65(4), 374 - 80
{Mycological and clinical study of cryptococcosis in Yokohama City University Hospital during the period from 1965 to 1989}; Kaminaga Y et al.; Among patients examined at the Central Laboratory of Yokohama City University Hospital over the 25 years from 1965 to 1989, those whose clinical samples showed Cryptococcus were studied in greater detail . The following findings were obtained . Of 16 patients who were found to have cryptococcosis, 14 (87.5%) were treated at the department of internal medicine, and one each at the departments of neurosurgery and dermatology . A study of these patients in terms of clinical type revealed 10 patients (62.5%) with meningitis, two with pneumonia and one with sepsis . The remaining three patients had complicated diseases: meningitis with sepsis, pneumonia with cutaneous cryptococcosis, or pleuritis with sepsis . Underlying disease, including liver cirrhosis, leukemia, multiple myeloma, malignant lymphoma and collagen disease, was found in 6 patients (37.5%), who were all from the department of internal medicine . All patients but one were given antimycotic agents . They were treated by a combination therapy except for three patients who received single amphotericin B (AMPH) therapy . The most frequent combination was AMPH + 5-flucytosine (5-FC), which was found in 7 cases . Seven patients (43.4%) died, three males and four females . Analysis of these cases in terms of clinical type revealed meningitis in four, and pneumonia, sepsis, or pleuritis complicated with sepsis in the remaining three patients . Four patients (57.1%) had underlying diseases . In addition, eleven strains isolated from the specimens were examined for serotypes and minimum inhibitory concentration (MIC) using three types of antimycotic agents . Serotypes of Cryptococcus neoformans were all A and the MIC was 0.1-0.39 micrograms/ml for AMPH, 0.05-0.2 micrograms/ml for 5-FC and 0.2-0.78 micrograms/ml for miconazole (MCZ).

Antimicrob Agents Chemother, 1991 Apr, 35(4), 726 - 9
Combined therapy with fluconazole and flucytosine in murine cryptococcal meningitis; Allendoerfer R et al.; To assess the possible beneficial effects of combined therapy (fluconazole and flucytosine) in the treatment of cryptococcal meningitis in the immunocompromised host, we compared therapy with fluconazole and flucytosine, individually and combined, in the experimental murine model . BALB/c athymic (nu/nu) mice were infected intracerebrally with 150 to 300 CFU of Cryptococcus neoformans . In mortality studies, treatment was initiated 24 h postinfection and continued for 10 to 14 days with either fluconazole (1 to 15 mg/kg of body weight per day), flucytosine (60 to 120 mg/kg/8 h), both drugs, or 0.3% Noble agar (control) . Combined therapy delayed mortality significantly when compared with controls and single-drug regimens . This was observed over a broad range of doses . Quantitative determinations of CFU in brain tissue demonstrated a significantly lower burden of C . neoformans in mice receiving combined therapy . The results indicate that combined therapy with fluconazole and flucytosine is superior to single-drug therapy.

Antimicrob Agents Chemother, 1991 Apr, 35(4), 615 - 21
Amphotericin B lipid complex therapy of experimental fungal infections in mice; Clark JM et al.; The amphotericin B lipid complex (ABLC), which is composed of amphotericin B and the phospholipids dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol, was evaluated for its acute toxicity in mice and for its efficacy in mice infected with a variety of fungal pathogens . ABLC was markedly less toxic to mice when it was administered intravenously; it had a 50% lethal dose of greater than 40 mg/kg compared with a 50% lethal dose of 3 mg/kg for Fungizone, the desoxycholate form of amphotericin B . ABLC was efficacious against systemic infections in mice caused by Candida albicans, Candida species other than C . albicans, Cryptococcus neoformans, and Histoplasma capsulatum . ABLC was also efficacious in immunocompromised animals infected with C . albicans, Aspergillus fumigatus, and H . capsulatum . Against some infections, the efficacy of ABLC was comparable to that of Fungizone, while against other infections Fungizone was two- to fourfold more effective than ABLC . Against several infections . Fungizone could not be given at therapeutic levels because of intravenous toxicity . ABLC, with its reduced toxicity, could be administered at drug levels capable of giving a therapeutic response . ABLC should be of value in the treatment of severe fungal infections in humans.

Mol Immunol, 1991 Apr-May, 28(4-5), 465 - 70
Differences in Cryptococcus neoformans capsular polysaccharide structure influence assembly of alternative complement pathway C3 convertase on fungal surfaces; Washburn RG et al.; Binding of complement component C3 and Factor B to Cryptococcus neoformans serotypes A through D via the alternative complement pathway was measured in a system containing fresh nonimmune human serum . Serotypes B and C (C . neoformans var . gattii) bound approximately half as many molecules of both complement components as serotypes A and D (C . neoformans var . neoformans) . In contrast, removal of xylosyl and glucuronyl side chains from the mannan main chain of capsular polysaccharide by the Smith degradation procedure resulted in binding of similar quantities of C3 to each of the four serotypes . We conclude that the relatively high degree of side chain substitution of capsular polysaccharide from C . neoformans variety gattii contributes to inefficient surface assembly of the alternative pathway C3 convertase . Inefficient binding of alternative pathway complement components to serotypes B and C may contribute to the relative difficulty in successfully treating infections caused by these organisms.

J Trop Med Hyg, 1991 Apr, 94(2), 116 - 7
Internuclear ophthalmoplegia in cryptococcal meningitis; Sung JY et al.; Cranial nerve involvement has been reported in cryptococcal infection of the central nervous system . We report a case of unilateral internuclear ophthalmoplegia developed in one patient with cryptococcal meningitis . The symptom subsided one week after commencement of antifungal treatment . We believe that this is a vasculitic phenomenon of the disease.

J Infect Dis, 1991 Apr, 163(4), 866 - 9
Hepatic involvement in patients with human immunodeficiency virus infection: discrepancies between AIDS patients and those with earlier stages of infection; Prufer-Kramer L et al.; The effect of human immunodeficiency virus (HIV) infection on type and severity of liver disease was studied in 61 HIV-positive patients who did not have AIDS and in 45 AIDS patients . Liver biopsies revealed viral hepatitis in 12 of 18 non-AIDS patients but in only 4 of 34 AIDS patients (P less than .0005, Fisher's exact test) . Acute, non-A non-B, and chronic active hepatitis B were seen exclusively in the non-AIDS group; however, chronic persistent hepatitis B was seen in both groups . In 9 of 18 AIDS patients intra vitam liver histopathology established diagnoses of opportunistic infections or tumors . Tissue reaction to certain pathogens, such as hepatitis B virus, mycobacteria, and cryptococci, seems to be milder in AIDS patients than in others who are HIV positive or the expected reaction of the normal host . This is likely because of impaired cell-mediated immunity in patients with advanced HIV disease.

Infect Immun, 1991 Apr, 59(4), 1489 - 99
Responses of murine natural killer cells to binding of the fungal target Cryptococcus neoformans; Hidore MR et al.; Natural killer (NK) cells bind to and inhibit the growth of the fungal target Cryptococcus neoformans . Since C . neoformans is structurally and chemically distinct from the standard tumor cell target used in the model of NK cell-mediated cytotoxicity, this study was designed to investigate the NK cell response after binding to cryptococci . Transmission electron micrographs and three-dimensional reconstructions of NK cell-cryptococci conjugates demonstrated focusing of the NK cell centrioles and Golgi apparatus toward the cryptococcal attachment site . NK cell cytoskeletal changes after cryptococcal binding were confirmed by immunofluorescence studies in which NK cells were allowed to bind to cryptococci in Mg2(+)-containing, Ca2(+)-free medium . One hour after the addition of Ca2+ to the preformed conjugates, the bound NK cells demonstrated a significant increase in the percentage of microtubule organizing centers focused toward the cryptococcal binding site . Colchicine, a drug that inhibits microtubule assembly, did not affect NK cell-cryptococci binding but abrogated NK cell-mediated cryptococcal growth inhibition, indicating that microtubule assembly, an important prerequisite for the secretory process, is not required for NK cell-cryptococci binding but is essential for inhibition of cryptococcal growth . In addition, the Ca2+ channel-blocking reagents, lidocaine and verapamil, did not affect NK cell-cryptococci binding but blocked the NK cell-mediated anticryptococcal activity, suggesting that a Ca2+ flux is essential for inhibition of cryptococcal growth . Considered together, these data indicate that NK cells respond to binding of a target cell that has a capsule and cell wall, in addition to a cell membrane, in a manner similar to that seen following binding to target cells that are surrounded by only a cell membrane; however, the response of the NK cells to the binding of C . neoformans is slower and possibly less efficient than the response after tumor cell binding.

Infect Immun, 1991 Apr, 59(4), 1476 - 88
Binding interactions of murine natural killer cells with the fungal target Cryptococcus neoformans; Murphy JW et al.; Murine natural killer (NK) cells have been shown to inhibit the growth of the yeastlike organism Cryptococcus neoformans both in vivo and in vitro . An essential first step in NK cell-mediated damage of cryptococcal cells is the binding of the NK cell to the cryptococcal cell . The studies presented here focused on the binding event . Electron photomicrographs and three-dimensional reconstructions of NK cell-C . neoformans conjugates show that NK cells bind to cryptococci through many microvilli . This is in contrast to the broad membrane-membrane interactions which form the binding site of NK cell-YAC-1 tumor cell conjugates . NK cell binding to cryptococci is much slower than NK cell binding to YAC-1 targets . Maximal conjugate formation with cryptococcal targets is reached after 2 h, whereas maximal conjugate formation with YAC-1 targets is obtained after 20 min . Once maximum NK cell-C, neoformans conjugate formation is obtained, another 4 h is required before damage to the cryptococcal cells can be detected with the CFU assay . These data indicate that the binding and action of NK cells on C . neoformans cells requires considerably more time than is necessary for similar events to occur in the NK cell-tumor cell model . NK cell membrane integrity is necessary for NK cells to bind to tumor targets, since some disruption of membrane integrity with 0.1 M dimethyl sulfoxide reduces conjugate formation and tumor cell lysis . In contrast, 0.1 M dimethyl sulfoxide did not diminish NK cell binding to cryptococcal targets; however, it significantly reduced cryptococcal growth inhibition . Although we have observed several differences in NK cell binding to the cryptococcal target compared with NK cell binding to tumor cell targets, there are some similarities in binding interactions of NK cells with the two different targets . Disulfide bonding appears to play a role in the binding of NK cells to both targets, since 5 mM 2-mercaptoethanol, a reagent that reduces disulfide bonds, prevented NK cells from binding to the tumor targets as well as the cryptococcal targets . Actin filaments, components of the cytoskeletal network, must be intact for NK cells to bind to YAC-1 cells or cryptococci . Taken together, our data confirm that binding of NK cells to the cryptococcal target is prerequisite to the stages that result in damage to the cryptococcal cell and that there are similarities and differences in NK cell-binding interactions with structurally different target cells.

Rev Invest Clin, 1991 Apr-Jun, 43(2), 133 - 8
Natural killer cell-mediated cytotoxicity in cryptococcal meningitis; Gonzalez-Amaro R et al.; There are evidences regarding the role of NK cytotoxic activity in the resistance against experimental C . neoformans infection . To assess the status of NK cell activity in human C . neoformans infection, we studied the peripheral blood of twelve patients with cryptococcal meningitis, six patients with CNS disease different to cryptococcal meningitis, and twelve healthy subjects . The number of CD16+cells and the NK cytotoxic activity of peripheral blood mononuclear cells was studied . The in vitro effect of exogenous IL-2 and interferon gamma on such cytotoxic activity was also studied . The number of CD16+ cells was not significantly different in patients compared to controls . However, cryptococcal patients exhibited a significant lower NK activity compared to both control groups (p less than 0.05 in both cases) . The low NK activity of cryptococcal patients was fully reconstituted in vitro with the addition of rIL-2 but not with rIFN gamma . In vitro experiments suggest that the low NK activity of cryptococcal meningitis patients is not due to amphotericin B therapy or blockade of NK cells by C . neoformans-derived molecules . The results of this study suggests that patients with cryptococcal meningitis have a defective NK cytotoxic function and may aid to understand the pathogenesis of this disease.

J Nutr Sci Vitaminol (Tokyo), 1991 Apr, 37(2), 173 - 84
Utilization and metabolism of {U-14C}4' galactosyllactose (O-beta-D-galactopyranosyl-(1----4)-O-beta-D-galactopyranosyl-(1----4)- D-glucopyranose) in rats; Ohtsuka K et al.; O-beta-D-Galactopyranosyl-(1----4)-O-beta-D-galactopyranosyl- (1----4)-D-glucopyranose (designated as 4'GL) are produced from lactose with Cryptococcus laurentii OKN-4 . Excretion and metabolism of 4'GL in rats were examined using a radioisotope technique . {U-14c}4'GL was synthesized from {U-14C}lactose by Cryptococcus laurentii OKN-4 . The 14CO2 in expired air was counted after oral administration of {U-14C}4'GL or {U-14C}lactose in conventional rats, rats treated with antibiotics and germ-free rats . The rate of 14CO2 excretion from conventional rats given {U-14C}4'GL was slower than that from those administered {U-14C}lactose . When {U-14C}4'GL was orally administered to rats given antibiotics, there was a 2-h delay in 14CO2 excretion, as compared to conventional rats . In germ-free rats, total excretion of 14CO2 from {U-14C}-4'GL decreased to about one-third of that of conventional rats during a 24-h period . Radioactivities in the serum, liver, and carcass of the {U-14C}4'GL oral administration group were lower than those of the {U-14C}lactose oral administration group . Radioactivities in the feces and urine however, were higher in {U-14C}4'GL group than in {U-14C}lactose group.

J Clin Microbiol, 1991 Apr, 29(4), 810 - 2
Rapid method to extract DNA from Cryptococcus neoformans; Varma A et al.; A rapid and easy method for the extraction of total cellular DNA from Cryptococcus neoformans is described . This procedure modifies and considerably simplifies previously reported methods . Numerous steps were either eliminated or replaced, including preincubations with cell wall permeability agents such as beta-mercaptoethanol and dithiothreitol . The commercially available enzyme preparation Novozyme 234 was found to contain a potent concentration of DNases which actively degrade DNA . Degradation and loss of DNA was prevented by maintaining a high concentration of EDTA in the lysing solution . This procedure resulted in high yields (150 to 200 micrograms of DNA from 100 ml of culture) of good-quality (undegraded), high-molecular-weight DNA which was readily digested by restriction endonucleases, making it suitable for use in various molecular applications.

Nihon Kyobu Shikkan Gakkai Zasshi, 1991 Apr, 29(4), 444 - 51
{Immunohistochemical analysis of granulomatous lung lesion in primary pulmonary cryptococcosis}; Miyazaki E et al.; Immunohistochemical analysis was performed in a case of pulmonary cryptococcosis that showed granulomatous pneumonia . The patient had no immunologic defects or other diseases . To cryostat sections, the immunocytes in granulomatous lesion were examined by application of monoclonal antibodies for T-lymphocytes, B-lymphocyte, macrophage series cells, lymphokines containing gamma interferon (gamma IFN), interleukin 1 (IL-1) and interleukin 2 (IL-2), and interleukin 2 receptor (IL-2R) . CD2+ cells, CD3+ cells and CD4+ cells were in and around the granulomas . On the other hand, CD8+ cells were around the granulomas . In granulomatous lesions, the CD4/CD8 ratio was 2.0 . Some T-lymphocytes were considered as activated lymphocytes showing OKDR+, IL-2+, gamma IFN+ or IL-2R+ . The lymphoid cells that aggregated near the granulomas were B-lymphocytes showing CD21+, CD24+, s-IgD+, s-IgM+, OKDR+ . According to these results they were mature B lymphocytes . Alveolar macrophages (AMs) were CD11+, CD36+, IL-1+, OKDR+ . Epithelioid cells were CD4+, CD11+, CD36+, OKDR+, IL-1+, IL-2R+ . CD1+ cells showing dendritic forms were scattered in granulomas . They were recognized to be Langerhans giant cells . These results suggest that in pulmonary cryptococcosis the formation of epithelioid cell granulomas is mainly induced by CD4+ cells (helper/inducer T-lymphocytes) . Additionally, Langerhans giant cells and mature B lymphocytes may be related to humoral immunity in pulmonary cryptococcosis.

J Chemother, 1991 Apr, 3(2), 130 - 3
Skull, patella and thigh cryptococcosis after a crashing injury of the temporal bone; Dounis E et al.; An unusual case of triple location (skull, patella and thigh) Cryptococcus neoformans is described . The peculiarity of the case is based on the probability of direct post-traumatic bone inoculation, subsequent seeding from skull to patella, thigh and cerebral spinal fluid (CSF), patella involvement, lack of evidence of lung involvement and lack of predisposing underlying disease . The response to surgery and a combination of amphotericin B and 5-flucytosine administration was favorable without relapse at follow-up after 7-year discontinuation of therapy.

Antonie Van Leeuwenhoek, 1991 Apr, 59(3), 177 - 81
Cryptococcus yarrowii sp . nov., a novel yeast species from Portugal; Fonseca A et al.; A novel species of the basidiomycetous genus Cryptococcus is described as Cr . yarrowii based on the study of an isolate from a decayed mushroom collected in Portugal . DNA-DNA homology with the type strain of the phenotypically similar species Cr . albidus was 10 +/- 2%.

Nihon Kyobu Shikkan Gakkai Zasshi, 1991 Apr, 29(4), 420 - 8
{Clinical features of 32 cases of fungal pneumonia}; Fujishita M et al.; A total of 32 patients with mycoses other than cavity-formed aspergilloma were reviewed . The main pathogenic fungi were Aspergillus in 14, Candida in 8, Cryptococcus in 4, Trichosporon in 4 and Mucor in 2 . Coinfection by two species was detected in 3 cases: Trichosporon and Aspergillus in 2 and Aspergillus and Candida in 1 . The underlying diseases were hematologic malignancies in all cases except 1 case of lung cancer . The hematologic malignancies were mostly leukemias of various types . Cryptococcosis developed in patients given long-term corticosteroid treatment but not in leukemic patients . All cases of aspergillosis, candidiasis and mucormycosis were due to nosocomial infection . On the other hand, 3 of 4 cases of cryptococcosis or trichosporonosis were attributable to community-acquired infection . Two of 4 trichosporonosis cases were considered to have been acquired during 2-day home stays . The diagnosis of pulmonary mycosis was made pathologically in 18 and clinically in 14 cases . Of the latter, 6 cases had an air-crescent sign on chest X-ray films and 8 cases were culture-positive . Extrapulmonary involvement was seen in all 16 cases of candidiasis, cryptococcosis and trichosporonosis but not in 10 of 14 aspergillosis cases . Severe granulocytopenia was present in all cases except 4 cases of cryptococcosis and 3 cases of aspergillosis . Chest X-ray findings of aspergillosis were of two types: one was an air-crescent sign which was noted in the recovery phase from leukopenia and the other was gradually enlarging consolidation which was bound by the interlobar fissure and progressed to lobar penumonia . A diffuse granular shadow was not characteristic of any fungus species.(ABSTRACT TRUNCATED AT 250 WORDS)

J Antimicrob Chemother, 1991 Apr, 27(4), 535 - 48
Tissue distribution and bioactivity of amphotericin B administered in liposomes to cancer patients; Collette N et al.; Amphotericin B concentration was measured by high-pressure liquid chromatography (HPLC) and by bioassay in tissues of 11 cancer patients who died from infection and/or their underlying disease after having received amphotericin B entrapped into sonicated liposomes (ampholiposomes) . These concentrations were compared to those measured in 28 patients who had only received the commercially available preparation of amphotericin B-Na deoxycholate complex (Fungizone) . The fungistatic and fungicidal titres of the tissue homogenates were also evaluated using two strains of Candida spp . and one strain of Cryptococcus neoformans to determine the bioactivity of amphotericin B incorporated in our liposomes . Tissue concentrations varied with the tested tissues and were correlated with the total dose of amphotericin B administered whether given as amphotericin B-Na deoxycholate or ampholiposomes . Amphotericin B concentrations measured by bioassay in tissue methanolic extracts reached 58-81% of concentrations measured by HPLC, whereas only 15-41% was recovered from the unextracted homogenates . Fungicidal titres were seldom measured in tissues, but fungistatic titres were observed and were linearly correlated with amphotericin B concentration measured by HPLC . These results were similar for the patients who received only amphotericin B-Na deoxycholate and for those who received both preparations (amphotericin B-Na deoxycholate and ampholiposomes) . Our results suggest that the tissue distribution of amphotericin B is not significantly modified by the type of preparation (deoxycholate complex or liposomes) and that most of the tissue-bound amphotericin B is not bioactive . However, higher daily doses of amphotericin B can be administered safely when incorporated in liposomes and therefore high tissue concentrations may be obtained more rapidly with ampholiposomes than with amphotericin B-Na deoxycholate.

Infect Immun, 1991 Apr, 59(4), 1423 - 33
T cell-mediated immunity in the lung: a Cryptococcus neoformans pulmonary infection model using SCID and athymic nude mice; Huffnagle GB et al.; T cells are important in systemic anticryptococcal defenses, but a role in controlling an initial pulmonary infection has not been demonstrated . A murine model with intratracheal inoculation was developed to study the acquisition and expression of pulmonary T cell-mediated immunity against Cryptococcus neoformans . Infections with four strains of C . neoformans (305, 68A, 613D, and 52D) in two strains of mice (BALB/c and C57BL/6) were examined . Unencapsulated strain 305 and slowly growing strain 68A were readily controlled apparently by nonimmune pulmonary defenses, and no extrapulmonary dissemination was detected . Strain 613D grew progressively in the lungs and disseminated to the brain and spleen . Strain 52D initially grew rapidly in the lungs and disseminated to the spleen, but a clearance mechanism developed in the lungs after day 7 postinfection and in the spleen after day 28 . SCID and athymic nude mice were unable to clear a strain 52D pulmonary infection, and a lethal disseminated infection occurred . Pulmonary clearance could be adoptively transferred into SCID mice infected with strain 52D by use of immune T cells from the spleen and lungs and hilar lymph nodes of infected immunocompetent donors . Furthermore, pulmonary clearance was almost 100-fold better in SCID mice that received immune T cells from the lungs and hilar lymph nodes than in those that received immune T cells from the spleen, even though equivalent levels of delayed-type hypersensitivity were transferred by both cell populations . These adoptive transfer studies suggested that the lung and hilar lymph node T cells from immune animals either are enriched in such a way as to mediate protective immunity or home to the lungs better than do splenic T cells.

Kanho Hakhoe Chi, 1991 Apr, 21(1), 5 - 15
{The effect of ethanol administration on the immune response of mice}; Kim KJ; The present study was undertaken in an effort to investigate the effects of alcohol on survival of mice and on their humoral and cellular immune responses . The immune responses examined were Arthus and delayed-type hypersensitivity (DTH) reactions to sheep red blood cells (SRBC), contact hypersensitivity to dinitrofluorobenzend (DNFB), antibody response to thymus-dependent SRBC and to thymus-independent polyvinylpyrroridone (PVP), and the recovery of Cryptococcus neoformans from the liver, spleen, kidney and brain of experimentally infected mice . The administration of ethanol concentrations of 20% or less did not cause any change in survival rates as compared with saline injected control group . In general, ethanol administration inhibited the Arthus and DTH reactions to SRBC, contact hypersensitivity to DNFB, and antibody response to both SRBC and PVP and it also decreased the resistance of mice to C . neoformans infection . Taken together, the present study strongly suggested that ethanol inhibits immune response and decreases the resistance of mice to C . neoformans infections.

Rev Cubana Med Trop, 1991 Apr-Aug, 43(2), 100 - 3
{Identification of varieties of Cryptococcus neoformans by the use of culture media}; Fernandez Andreu C et al.; Ten Cryptococcus neoformans strains of human origin were studied in order to know their variety by using 2 different culture mediums: creatinine-bromothymol-blue-dextrose and glycine-cycloheximide-phenol red . The results obtained in the two mediums were not totally coincidental . The possible causes and the specificity of these mediums for identifying C . neoformans varieties are discussed.

J Exp Med, 1991 Apr 1, 173(4), 793 - 800
Immunity to a pulmonary Cryptococcus neoformans infection requires both CD4+ and CD8+ T cells; Huffnagle GB et al.; The role of CD4+ and CD8+ T cells in mediating pulmonary clearance of a cryptococcal infection was investigated . Intratracheal inoculation of BALB/c and C.B-17 mice with a moderately virulent strain of Cryptococcus neoformans (52D) resulted in a pulmonary infection, which was cleared by a T cell-dependent mechanism . During this clearance, there was a significant influx of both CD4+ and CD8+ T cells into the lungs . Depletion of CD4+ T cells by injections of CD4-specific monoclonal antibody (mAb) prevented pulmonary clearance and also resulted in significant colonization of the brain and spleen of infected mice . CD4 depletion did not prevent the influx of CD8+ T cells into the lungs . Surprisingly, depletion of CD8+ T cells by mAb also ablated pulmonary clearance . CD8-depleted mice also had a small but significant increase in brain and spleen colony-forming unit compared to control mice by the end of the study . CD4+ T cell pulmonary influx was independent of the presence of CD8+ T cells . The lungs of T cell-depleted mice were examined histologically . CD4+ and CD8+ T cells each mediated a degree of inflammatory influx seen in the lungs of infected mice and raised the possibility that CD4+ and CD8+ T cells may synergize to generate the inflammatory response in the lungs . Numerous phagocytized but intact cryptococci were seen in the inflammatory foci of CD8-depleted mice but not in control or CD4-depleted mice . We propose that CD4+ T cells may recruit and activate effector phagocytes while CD8+ T cells predominantly function to lyse cryptococcus-laden unactivated phagocytes similar to the function of CD8+ T cells during listeria and mycobacteria infections.

Arzneimittelforschung, 1991 Apr, 41(4), 443 - 8
Spectrum of in vitro antifungal activity of ditiocarb sodium; Allerberger F et al.; The immunomodulator ditiocarb sodium (sodium diethyldithiocarbamate, DTC, CAS 148-18-5) is finding increasing use in treating AIDS-patients . Using a macro broth dilution method the minimal inhibitory concentrations and minimal fungicidal concentrations of DTC were studied for 76 fungal strains (54 species) and a broad spectrum of direct antifungal activity was found . All 6 Candida albicans strains tested were inhibited by 1.2 micrograms DTC/ml, a concentration achievable by i.v . administration of DTC in doses as presently used for immunomodulation . All strains of Cryptococcus were inhibited by DTC in concentrations of 2.5 micrograms/ml . In combination with amphotericin B, DTC showed a synergistic mode of action for 6 out of 7 Cryptococcus neoformans strains (checkerboard technique) . As far as the direct antifungal activity of DTC was tested (11 strains, 5 species), the combination with amphotericin B or flucytosine showed no antagonistic mode of action . The augmentation of host defences by the immunomodulating agent DTC could become an adjunct to conventional therapy in immunocompromised patients with systemic fungal infections.

Antimicrob Agents Chemother, 1991 Apr, 35(4), 707 - 13
High-dose itraconazole in the treatment of severe mycoses; Sharkey PK et al.; Eight patients with systemic mycoses and with prior treatment failures were treated with itraconazole (600 mg/day) for a mean duration of 5.5 months . All six patients without AIDS experienced improvement or stabilization of their fungal infections while receiving high-dose itraconazole, although two patients later experienced treatment failures, one by relapse and one by progression, on lower doses . Treatment failures also occurred in the two patients with AIDS and cryptococcal meningitis . The failures were associated with low serum itraconazole concentrations (less than 2.5 micrograms/ml) in both patients . All other patients had mean trough levels in serum above 5 micrograms/ml . One patient who was improving on 600 mg/day developed a progressive infection after reduction of the dose to 400 mg/day . Side effects included reversible adrenal insufficiency in one patient; severe hypokalemia, mild diastolic hypertension, and rhabdomyolysis in one patient; mild hypokalemia and hypertension in four other patients; and breast tenderness in one patient . The mean decrease in serum potassium during treatment was statistically significant (P = 0.05) . Selected patients with severe systemic mycoses may benefit from prolonged high-dose itraconazole treatment . However, 600 mg/day may be approaching the upper limits of acceptable dosing for long-term treatment.

J Immunol Methods, 1991 Mar 21, 137(2), 167 - 73
Ultrasensitive assays for endogenous antimicrobial polypeptides; Lehrer RI et al.; We developed two sensitive methods for identifying antimicrobial molecules in leukocytes and other tissues . One method uses a gel overlay technique and was designed to identify antimicrobial polypeptides in samples subjected to polyacrylamide gel electrophoresis . The other, a radial diffusion assay, allows multiple fractions obtained by chromatographic procedures to be tested for antimicrobial activity conveniently . When we used E . coli ML-35p or Salmonella typhimurium 14028S as test organisms in the radial diffusion assay, we routinely detected 5-10 ng of rabbit defensin NP-1 in 5 microliters of sample . With minor modifications, both methods can be applied to other organisms, including Gram-positive bacteria, several Candida species and Cryptococcus neoformans.

Nippon Saikingaku Zasshi, 1991 Mar, 46(2), 509 - 14
{Antifungal and fungicidal activities of tea extract and catechin against Trichophyton}; Okubo S et al.; We examined tea extract, (-) epigallocatechin gallate (EGCg) and theaflavin digallate (TF3) for their antifungal and fungicidal activities against Trichophyton mentagrophytes, T . rubrum, Candida albicans and Cryptococcus neoformans . Tea extract (2.5%) inhibited completely the growth of both T . mentagrophytes and T . rubrum . EGCg at 2.5 mg/ml failed to inhibit their growth, whereas TF3 at 0.5 mg/ml inhibited the growth . EGCg (1mg/ml) showed no fungicidal activity against Trichophyton . TF3 (1mg/ml) killed Trichophyton by a long time contact (72-96 hrs) . Tea extract showed a fungicidal activity against Trichophyton in a dose- and contact time-dependent manner . It did not inhibit the growth of C . albicans, but at a high concentration, inhibited slightly the growth of C . neoformans . It had no fungicidal activity against C . albicans or C . neoformans.

Clin Pharm, 1991 Mar, 10(3), 179 - 94
Fluconazole: a new antifungal agent; Kowalsky SF et al.; The chemistry, activity, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and administration of fluconazole are reviewed . Fluconazole is a triazole antifungal agent labeled for use in the treatment of oropharyngeal and esophageal candidiasis and cryptococcal meningitis . Like the imidazoles, fluconazole inhibits the C-14 demethylation of lanosterol, but it has little or no effect on mammalian cytochrome P-450 enzymes . Fluconazole's activity in vitro does not reflect its effectiveness in vivo . Pharmacokinetic characteristics include water solubility and excellent bioavailability, low protein binding, extensive tissue distribution, and penetration into the cerebrospinal fluid . Fluconazole is eliminated primarily by the kidneys; dosage adjustments are necessary in patients with renal insufficiency . Studies have shown fluconazole to be effective in patients with cryptococcal meningitis and candidiasis, but the superiority of fluconazole over such agents as amphotericin B, ketoconazole, clotrimazole, and itraconazole remains to be proved . Fluconazole has shown varying degrees of success in the treatment of other systemic mycoses . The adverse effects of fluconazole are relatively infrequent and are primarily gastrointestinal . Tolbutamide, warfarin, rifampin, cyclosporine, and phenytoin interact with fluconazole . The drug is available in both oral and intravenous formulations . Fluconazole is a broad-spectrum antifungal drug that appears to be similar in efficacy to other antifungals in the treatment of some systemic mycoses . More studies must be completed before fluconazole can be recommended as a first-line antifungal therapy.

Pneumologie, 1991 Mar, 45(3), 110 - 3
{Cryptococcal sepsis simulating miliary tuberculosis in malignant lymphoma}; Amthor M et al.; A malignant non-Hodgkin lymphoma (Cb-Cc) stage IVb was diagnosed in a man of 71 years of age . He was subjected to polychemotherapy . The mediastinum was irradiated . Cortisone therapy was performed because of irradiation pneumonitis . A highly febrile disease pattern developed with increasing dyspnoea while displaying the signs and symptoms of a miliary pulmonary disease . The treatment course was directed at combatting miliary tuberculosis . The patient died from cardiorespiratory failure . The postmortem examination supplied proof of cryptococcal sepsis . The differential diagnosis is discussed.

South Med J, 1991 Mar, 84(3), 394 - 6
Profound papilledema due to cryptococcal meningitis in acquired immunodeficiency syndrome: successful treatment with fluconazole; Good CB et al.; Although cryptococcal meningitis is a frequent infection in patients with AIDS, papilledema is rarely reported . We have reported a case of profound papilledema associated with cryptococcal meningitis in a patient with AIDS . After treatment failure with amphotericin B, the patient was successfully treated with fluconazole, and the papilledema resolved.

Gastroenterology, 1991 Mar, 100(3), 745 - 8
High-protein ascites in patients with the acquired immunodeficiency syndrome; Wilcox CM et al.; Diseases of the liver or peritoneum resulting in ascites have been infrequently reported in patients with the acquired immunodeficiency syndrome . Since 1985, eight noncirrhotic patients with the acquired immunodeficiency syndrome presenting with new onset high-protein ascites have been evaluated . All but one patient had nondiagnostic paracentesis studies . Laparoscopy with biopsy of identified abnormalities or percutaneous omental biopsy were diagnostic in four patients . Non-Hodgkin's lymphoma was the cause in three patients, and disseminated cryptococcosis occurred in one patient . In the four other patients, chronic nonspecific peritonitis was found at laparoscopy; follow-up of these latter patients, including exploratory laparotomy in one patient and autopsy in two patients, disclosed no specific cause . Patients with the acquired immunodeficiency syndrome and high-protein ascites of uncertain etiology should undergo directed peritoneal evaluation as a potentially treatable disorder may be found . However, despite extensive evaluation, a subset of patients in whom no specific cause can be identified still remains.

AJNR Am J Neuroradiol, 1991 Mar-Apr, 12(2), 283 - 9
Intracranial cryptococcosis in immunocompromised patients: CT and MR findings in 29 cases; Tien RD et al.; CT and MR scans of 29 immunocompromised patients (28 with AIDS or ARC, one with diabetes mellitus) who had documented intracranial cryptococcal infection were reviewed retrospectively . All patients had CT studies; 26 received iodinated contrast agent . CT findings included normal results in nine of 29, atrophy only in 13 of 29, nonenhancing lesions in three of 29, enhancing lesions in two of 20, and foci of leptomeningeal calcification in two of 29 . Ten patients had both CT and MR studies, and four received gadopentetate dimeglumine . Among these 10 patients, five had normal CT studies and one showed moderate central atrophy . All 10, however, had abnormal MR findings . We observed four patterns: (1) parenchymal cryptococcoma (3/10); (2) numerous clustered tiny foci that were hyperintense on T2-weighted images and non-enhancing on postcontrast T1-weighted images, located relatively symmetrically in the basal ganglia bilaterally and in midbrain, representing dilated Virchow-Robin spaces (4/10); (3) multiple miliary enhancing parenchymal and leptomeningeal nodules (1/10); and (4) a mixed pattern, consisting of dilated Virchow-Robin spaces with mixed lesions such as cryptococcoma and miliary nodules (2/10) . In the group of six patients with dilated Virchow-Robin spaces (patterns 2 and 4), two received gadopentetate dimeglumine, but the Virchow-Robin space lesions did not enhance; among the remaining four patients, two received gadopentetate dimeglumine (one with pattern 1 and one with pattern 3) and the lesions did enhance . Three patients in our study subsequently died and autopsies were performed . The postmortem results revealed dilated Virchow-Robin spaces filled with fungi in the basal ganglia, which correlated well with MR findings.(ABSTRACT TRUNCATED AT 250 WORDS)

J Exp Med, 1991 Mar 1, 173(3), 755 - 8
Intrapulmonary growth and dissemination of an avirulent strain of Cryptococcus neoformans in mice depleted of CD4+ or CD8+ T cells; Hill JO et al.; The contribution of T lymphocyte subpopulations to intrapulmonary and systemic resistance against an opportunistic strain of Cryptococcus neoformans was examined . It was found that C . neoformans was destroyed when introduced into the lungs of normal mice, but disseminated to the brains of mice treated with an antibody that depleted them of CD4+ T cells . Depletion of either CD8+ or CD4+ T cells impaired the ability of the host to clear the yeast from the lung . These results, together with the observation that CD8+ T cells accumulate in the lungs of CD4+ T cell-deficient mice, suggest that CD8+ T cells play an important role in resistance to C . neoformans infection acquired via the respiratory tract.

Chest, 1991 Mar, 99(3), 765 - 6
Pericarditis with tamponade due to cytomegalovirus in the acquired immunodeficiency syndrome; Nathan PE et al.; A 35-year-old male homosexual with AIDS presented with headache and fever and was found to have cryptococcal meningitis . During the patient's hospital course, his hemodynamic status deteriorated as a result of pericardial tamponade . Antemortem analysis of the fluid was unrevealing; however, postmortem examination of the pericardium revealed typical intranuclear inclusions of cytomegalovirus infection . Cytomegalovirus should be included in the differential diagnosis of pericardial effusion in patients with AIDS.

J Gen Microbiol, 1991 Mar, 137 ( Pt 3), 455 - 64
A cell surface/plasma membrane antigen of Candida albicans; Li RK et al.; Antibody from BALB/cByJ mice immunized against a membranous fraction of Candida albicans agglutinated whole cells as well as the membranous fraction . Hybridoma techniques were used to isolate an IgM monoclonal antibody (mAb) designated 10G which agglutinated whole cells and reacted with the subcellular fraction . Yeast cells of 15 additional C . albicans strains and isolates of C . stellatoidea, C . tropicalis, C . intermedia and C . lusitaniae were also agglutinated by mAb 10G . The antigen was not detected on other fungi, including Candida krusei, C . utilis, Cryptococcus neoformans, Cr . albidus, Torulopsis glabrata, Rhodotorula spp . and Saccharomyces cerevisiae . To determine the cellular location of the epitope to which mAb 10G is specific, freeze-substitution was compared with traditional chemical fixation methods in preparation of samples for immunocolloidal gold electron microscopy (IEM) . With both fixation procedures, the antigen recognized by mAb 10G was found randomly and densely concentrated on the plasma membrane on exponential-phase yeast-form cells and had a patchy distribution on the cell wall surface . Association of the antigen with the plasma membrane was confirmed by IEM of isolated membranes . On developing hyphal cells, antigen appeared first on the plasma membrane and later on the cell wall surface . Treatment of yeast cells with beta-mercaptoethanol and Zymolyase before fixation removed the antigen from the surface but left the cytoplasmic antigen undisturbed . Treatment of yeast cells or solubilized antigen with heat or proteolytic enzyme (trypsin, Pronase B, proteinase K) did not remove or destroy the antigen, suggesting a non-protein nature of the epitope.

N Engl J Med, 1991 Feb 28, 324(9), 580 - 4
A placebo-controlled trial of maintenance therapy with fluconazole after treatment of cryptococcal meningitis in the acquired immunodeficiency syndrome . California Collaborative Treatment Group; Bozzette SA et al.; BACKGROUND AND METHODS . In patients with the acquired immunodeficiency syndrome (AIDS), the rate of relapse after primary treatment for cryptococcal meningitis remains high . We conducted a controlled, double-blind trial to evaluate the efficacy of maintenance therapy with fluconazole . At entry into the study, all participants had sterile cultures of cerebrospinal fluid, blood, and urine after following a standardized course of therapy for culture-proved cryptococcal meningitis . The patients were randomly assigned to take either fluconazole or placebo as maintenance therapy . The dose of fluconazole was 100 mg daily in the first phase of study and 200 mg daily in the second phase . RESULTS . Of 84 patients initially enrolled, 16 (19 percent) were found to have silent, persistent infection on the basis of cultures that became positive after entry into the study; 7 other patients were lost to follow-up shortly after entry . Of the remaining 61 patients, 10 of 27 assigned to placebo (37 percent) and 1 of 34 assigned to fluconazole (3 percent) had a recurrence of cryptococcal infection at any site (difference in risk, 34 percent; 95 percent confidence interval, 15 to 53) . Of the 11 recurrent infections, 7 were detected in urine obtained after prostatic massage . There were four recurrent meningeal infections in the patients taking placebo, but none in those taking fluconazole (mean duration of follow-up, 164 days) (P = 0.03) . In multivariate analyses, the best predictors of recurrence-free survival were fluconazole treatment (P = 0.02; relative hazard, 13.2), a lower serum cryptococcal-antigen titer (P = 0.05; relative hazard, 1.2), and more prolonged primary therapy with flucytosine (P = 0.09; relative hazard, 1.1) . Survival and toxicity were similar in the two maintenance-treatment groups . CONCLUSIONS . In patients with AIDS, silent persistent infection is common after clinically successful treatment for cryptococcal meningitis . Maintenance therapy with fluconazole is highly effective in preventing recurrent cryptococcal infection.

N Z Med J, 1991 Feb 27, 104(906), 57 - 9
Cryptococcal meningitis in Auckland 1969-89; Hutchinson DO et al.; Twenty-six patients with cryptococcal meningitis were seen in Auckland between 1969 and 1989 . The incidence of cryptococcal meningitis in Auckland residents was 0.12 cases/100,000/year . Ten (38%) of the patients were Maori or Pacific Island Polynesians . Nineteen (73%) had a predisposing cause, including immunosuppressive therapy in nine and the acquired immunodeficiency syndrome (AIDS) in seven . The most common presenting syndrome was a subacute or chronic meningitis . Other clinical syndromes included a slowly progressive ataxia, polyradiculopathy, and headache with vomiting . In two patients, the symptoms of meningitis were overshadowed by those of systemic cryptococcal infection . Delay in making the diagnosis was common . The most sensitive method for diagnosing cryptococcal meningitis was the cerebrospinal fluid cryptococcal antigen test . Antifungal therapy cured 17 of the 25 (68%) treated patients overall, 15 of the 19 (79%) without AIDS and six of the seven with no underlying disease.

J Am Vet Med Assoc, 1991 Feb 15, 198(4), 655 - 6
Bronchoalveolar lavage and tracheal wash to determine lung involvement in a cat with cryptococcosis; Hamilton TA et al.; A one-year-old 3-kg female domestic shorthair cat was diagnosed as having cryptococcosis . Although the cat had no clinical signs referable to the pulmonary system and results of thoracic radiography were normal, organisms were recovered by use of tracheal wash and bronchoalveolar lavage . In cases of fungal infections, the latter 2 methods can be more reliable than radiography and evaluation of clinical signs for determining pulmonary involvement.

Kansenshogaku Zasshi, 1991 Feb, 65(2), 200 - 8
{Clinical and pathological analysis of deep mycoses}; Ohsawa H; Clinical and pathological analysis were performed on 127 cases of deep mycoses diagnosed by autopsy during the 24 years between 1964 and 1987 in Juntendo University Hospital . The following findings were obtained . 1) There has been a tendency for the number of mycoses to increase each year, especially notable for candidiasis and aspergillosis . 2) Underlying diseases were, in order of incidence, various hematologic diseases, solid tumors, inflammatory diseases and collagen diseases; the most common were various types of leukemia . 3) Candidiasis was often observed in patients with gastrointestinal tract cancers . Aspergillosis was often observed in patients with collagen diseases . 4) Regarding the visceral distribution of mycoses, aspergillosis was observed in the lung, candidiasis was observed in the lung, kidney and intestinal tract in decreasing order, and cryptococcosis was also observed in the lung and central nervous system . 5) There was a probability of fungal infections occurring in cases of lymphopenia . 6) A fever was present at the time of hospitalization in many cases of aspergillosis, and the presence of an indwelling catheter was a common feature in cases of candidiasis . 7) Fungemia was frequently observed in candidiasis, but very rarely in cases of aspergillosis . 8) The large amounts of corticosteroid hormones and blood transfusions were suspected as causative factors of fungal infections.

Can J Microbiol, 1991 Feb, 37(2), 128 - 35
Cryptococcosis in beige mice: the effect of congenital defects in innate immunity on susceptibility; Salkowski CA et al.; The influence of the beige (bg/bg) mutation on susceptibility to cryptococcosis was assessed by mortality, quantitative culturing, and histopathology of infected organs from bg/bg and bg/+ mice . Immunodeficient bg/bg mice were more susceptible to systemic cryptococcosis than immunocompetent bg/+ mice . Differences in susceptibility of bg/bg and bg/+ mice corresponded with temporal differences in histopathology . In contrast to bg/+ mice, inflammatory responses in infected tissues from bg/bg mice contained less cellular infiltrate, proportionally more polymorphonuclear neutrophils than monocytes and macrophages, and delays in the switch from acute to chronic inflammation . Enhanced growth of Cryptococcus neoformans in the internal organs of bg/bg mice was coincident with delayed inflammatory responses . These quantitative culture and histopathology studies suggest that the defects associated with monocytes and macrophages and polymorphonuclear neutrophils resulted in altered in vivo inflammatory responses and contributed to the enhanced susceptibility of beige mice to C . neoformans.

Yakugaku Zasshi, 1991 Feb, 111(2), 126 - 37
{Synthesis and antifungal activity of butenafine hydrochloride (KP-363), a new benzylamine antifungal agent}; Maeda T et al.; In screening of new antifungal agents, bis(naphthalenemethyl)amines were found to have more potent antifungal activity than clotrimazole . Studies on their structure-activity relationships indicated that benzylamines had potent antifungal activity . Among them, butenafine hydrochloride (N-p-tert-butylbenzyl-N-methyl-1-naphthalenemethylamine hydrochloride, KP-363) has proved to show the strongest activity . It exhibits a wide spectrum activity in vitro against particularly dermatophytes (87 strains; minimal inhibitory concentration (MIC) range, 0.0015 to 0.05 microgram/ml), and also against Aspergillus (15 strains; MIC range, 0.025 to 0.78 microgram/ml), Cryptococcus neoformans (4 strains; MICs 0.78 and 1.56 micrograms/ml) and yeasts of genus Candida (67 strains; MIC range, 3.13 to greater than 100 micrograms/ml).

Curr Opin Radiol, 1991 Feb, 3(1), 16 - 24
Infections of the central nervous system; Rauch RA et al.; Acquired immunodeficiency syndrome has had a major impact on all aspects of clinical neuroscience in the past few years . Thus understanding acquired immunodeficiency syndrome and its associated complications within the nervous system was a major component of this review of the past year's radiologic literature of infection in the central nervous system . Particular topics discussed include the appearance of primary human immunodeficiency virus infection of the brain as well as toxoplasmosis, cryptococcal infection, and progressive multifocal leukoencephalopathy . In addition, the association of acquired immunodeficiency syndrome with the appearance of lymphoma, myeloradiculopathy, and vascular disease are considered . The remainder of the literature on central nervous system infection in the past year generally concerned the imaging characteristics of unusual infections such as cysticercosis, paragonimiasis, tuberculosis, Lyme disease, viral infection, and nonspecific inflammation of the meninges . The availability of an MR imaging contrast agent (gadolinium) also provided important diagnostic information to the radiologist in the imaging of infection in the central nervous system.

J Clin Gastroenterol, 1991 Feb, 13(1), 58 - 64
Pancreatic involvement in human immunodeficiency virus infection; Bonacini M; Involvement of the pancreas by human immunodeficiency virus (HIV) infection has not been adequately addressed and is the object of this review . I analyzed the English language literature, including single case reports of pancreatic involvement and larger series reporting detailed pathological findings of patients with HIV infection . Nonspecific pathological changes in the pancreas are frequently seen at autopsy of HIV-infected patients, but are not more common than in controls . Several types of infections (mainly cytomegalovirus, Cryptococcus neoformans, and Mycobacteria) and neoplasms (lymphoma and Kaposi's sarcoma) can involve the pancreas because they are usually disseminated . Although the serum amylase may be elevated, the patient remains asymptomatic . Occasional instances of severe and even fatal pancreatitis have been reported with HIV infections and attendant drug toxicity . Pentamidine has a predictable incidence of hypoglycemic episodes and 2',3'-dideoxyinosine provokes pancreatitis in a minority of treated patients . Such drug toxicity seems to deserve greater clinical concern than opportunistic infections or neoplasms.

J Clin Microbiol, 1991 Feb, 29(2), 333 - 9
Performance of cryptococcus antigen latex agglutination kits on serum and cerebrospinal fluid specimens of AIDS patients before and after pronase treatment; Hamilton JR et al.; Cryptococcal antigen titers in 97 serum and 42 cerebrospinal fluid (CSF) specimens from 37 AIDS patients with culture-proven cryptococcal infection were determined with the Meridian kit (Meridian Diagnostics Inc., Cincinnati, Ohio) before and after treatment with pronase . The geometric mean titers before and after pronase treatment were 1:45 and 1:588 in serum and 1:97 and 1:79 in CSF, respectively . Only on serum (but not CSF) specimens after pronase treatment were (i) titers increased by 2 to 13 dilutions on 57% of the specimens, all of which had titers of less than or equal to 1:128 before pronase treatment, (ii) false-negative reactions on 27% of specimens before pronase treatment eliminated, all of which had titers from 1:4 to 1:4,096, (iii) prozone-like reactions (titer, less than or equal to 1:256) on 9% of the specimens before pronase treatment eliminated, and (iv) agglutination reactions on all specimens stronger and easier to interpret . Antifungal agents added to serum as well as freeze-thaw cycles did not change antigen titers in serum . After two separate tests, the same titers were obtained on 94% of 35 serum specimens that were treated with pronase and on 96% of 53 CSF specimens that were not treated with pronase . A total of 26 serum specimens and 28 CSF specimens from patients with no cryptococcal disease were negative before and after pronase treatment . The IBL kit (International Biological Labs Inc., Cranbury, N.J.) was compared with the Meridian kit on 41 serum specimens and 14 CSF specimens . Results from the two kits agreed on 54 and 68% of serum specimens and 86 and 93% of CSF specimens before and after pronase treatment, respectively . The IBL kit generally produced higher titers on specimens in disagreement and produced no prozone-like reactions . Routine pronase treatment of serum is recommended with the Meridian kit in order to eliminate false-negative and unclear agglutination reactions by producing a consistent interpretation of agglutination reactions . CSF specimens do not require pronase treatment . Titer results produced by the kits from the two different manufacturers varied considerably: the kits should not be used interchangeably for determining antigen titers in serum specimens.

Todays OR Nurse, 1991 Feb, 13(2), 21 - 4
AIDS and its effect on ophthalmology; Fong AC; 1 . Ocular manifestations of AIDS are, for the most part, due to the opportunistic infections and neoplasias seen in the syndrome . 2 . Ocular manifestations seen in AIDS patients include cytomegalovirus, Toxoplasma gondii, Candida sp, Cryptococcus sp, herpes simplex or zoste, Mycobacterium sp, and ocular syphilis . 3 . Handwashing and disinfection of instruments are recommended to prevent transmission of infection in the ophthalmic practice.

J Clin Invest, 1991 Feb, 87(2), 528 - 35
Binding of Cryptococcus neoformans by human cultured macrophages . Requirements for multiple complement receptors and actin; Levitz SM et al.; We studied the receptors on human cultured macrophages (MO-M phi) responsible for binding encapsulated and isogenic mutant acapsular strains of Cryptococcus neoformans, and whether such binding leads to a phagocytic event . Both strains required opsonization with complement components in normal human serum in order for binding to occur . Binding of the acapsular, but not the encapsulated, strain led to phagocytosis . MAb directed against any of the three defined complement receptors (CR) on MO-M phi (CR1, CR3, and CR4) profoundly inhibited binding of serum-opsonized encapsulated (and to a lesser extent acapsular) organisms to MO-M phi . Immunofluorescence studies demonstrated migration of CR to the area of the cryptococcal binding site . Trypsin and elastase inhibited binding of encapsulated and, to a lesser extent, acapsular yeasts to MO-M phi . Binding of encapsulated C . neoformans was profoundly inhibited by incubation in the cold or by inhibitors of receptor capping and actin microfilaments . Thus, multiple CR appear to contribute to binding of serum-opsonized encapsulated C . neoformans by MO-M phi . Binding is an energy-dependent process that requires conformational changes in actin yet does not lead to phagocytosis of the organism . In contrast, energy is not required for binding of acapsular yeasts by MO-M phi and binding triggers phagocytosis.

Chest, 1991 Feb, 99(2), 370 - 2
Utility of bronchoscopic sampling techniques for cryptococcal disease in AIDS; Malabonga VM et al.; Although cryptococcal pneumonia is a well recognized complication of the acquired immunodeficiency syndrome, optimal diagnostic approaches remain to be defined . During a 32-month period (October 1984 to June 1987), 11 patients were diagnosed with CP at our institution . The diagnosis was established in all 11 patients from specimens obtained via fiberoptic bronchoscopy (ten) and/or double-lumen catheter lavage (one) . Direct stains of sedimented bronchoalveolar lavage were positive for organisms characteristic of Cryptococcus neoformans in nine of 11 patients . Transbronchial biopsies were positive (special histologic stains) in six of eight patients; bronchial washings were positive (direct smear) in seven of ten patients, the bronchial brushings were positive on stain in six of nine patients, and in one patient, a Wang transbronchial needle aspirate was positive on stain . Fungal cultures were positive on the BAL in seven of 11 patients, and on the bronchial washings in four of ten patients; the TBBx culture samples were all negative (zero of three) . The serum cryptococcal antigen titer was elevated (median = 1:1024) in all eight patients in which it was assayed . Our data suggest that BAL and bronchial washings have a combined sensitivity on smear equal to that of TBBx and superior to that of TBBx fungal culture . The TBBx does not appear to be necessary in this setting . In addition, an elevated serum cryptococcal antigen titer appears to be an important adjunct in the evaluation of pulmonary infiltrates in AIDS.

Otolaryngol Head Neck Surg, 1991 Feb, 104(2), 265 - 9
Sudden hearing loss due to AIDS-related cryptococcal meningitis--a temporal bone study; Kwartler JA et al.; We have presented the clinical history and temporal bone findings in a patient who manifested sudden hearing loss, and who subsequently was found to have cryptococcal meningitis associated with AIDS . The histopathologic findings are similar to earlier reports in patients without AIDS . Because cryptococcal infection is so much more common in AIDS patients than in the general population, it must be considered a causative factor when presented with an AIDS patient with progressive or sudden hearing loss . This offers the patient a chance for timely and effective treatment.

Infect Immun, 1991 Feb, 59(2), 486 - 93
A monoclonal antibody to gamma interferon blocks augmentation of natural killer cell activity induced during systemic cryptococcosis; Salkowski CA et al.; These studies demonstrate that the cytotoxic activity of splenic natural killer (NK) cells is augmented in both nu/nu and nu/+ mice during systemic cryptococcosis . Both the kinetics and the regulation of NK cell activity differed in Cryptococcus neoformans-infected nu/nu and nu/+ mice . Greater augmentation was observed following challenge with 10(5) cells than with smaller inocula, and augmented NK cell activity was not always associated with enhanced control of systemic cryptococcosis . Infection with a nonencapsulated strain of C . neoformans induced an early but transient increase in splenic NK cell activity in nu/nu and nu/+ mice . Injection of capsular polysaccharide induced a transient augmentation of splenic NK cell activity in nu/+ mice but caused a persistent increase in splenic NK cell activity in nu/nu mice . In vivo treatment with monoclonal antibody to gamma interferon abrogated the augmentation of splenic NK cell activity induced during cryptococcal infections in both nu/nu and nu/+ mice and enhanced the susceptibility of nu/+ mice to C . neoformans to a greater extent than it did that of nu/nu mice . These results suggest that gamma interferon is an important mediator of resistance to C . neoformans.

Enferm Infecc Microbiol Clin, 1991 Feb, 9(2), 90 - 4
{16 cases of infection by Cryptococcosis neoformans in patients with AIDS}; Castro Guardiola A et al.; Sixteen patients with AIDS (6% of the total AIDS patients) who had infection by Cryptococcus neoformans were studied . Most of these patients (94%) had cryptococcal meningitis . Only 50% of the cases showed clinical manifestations of neurological involvement . Blood cultures and antigen level measurement were the diagnostic techniques with best results due to their high percentage of positivity . Sixty nine percent of patients survived the acute phase of the infection and only 3 of those who died in this period showed evidence of active infection patients by the fungus.

Ophthalmology, 1991 Feb, 98(2), 196 - 201
Resolution of microsporidial epithelial keratopathy in a patient with AIDS; Yee RW et al.; A patient with a positive human immunodeficiency virus (HIV) titer and cryptococcal meningitis suffered bilateral epithelial keratopathy caused by Encephalitozoon, which did not respond to sulfas, erythromycin, bacitracin, tobramycin, neomycin, polymyxin B, or fluconazole . Eventual administration of itraconazole for the meningitis apparently produced resolution of the long-lasting (2-month) ocular infection . This new oral triazole antifungal may be valuable against the increasingly prevalent microsporidial infections in patients with acquired immune deficiency syndrome . Debulking of the infection by corneal scraping may have contributed to the authors' success.

Infect Immun, 1991 Jan, 59(1), 29 - 35
Effects of Cryptococcus neoformans-specific suppressor T cells on the amplified anticryptococcal delayed-type hypersensitivity response; Buchanan KL et al.; Cell-mediated immunity is an important host resistance mechanism against Cryptococcus neoformans, the etiological agent of cryptococcosis . Previous studies from our laboratory have shown that the anticryptococcal cell-mediated immune response as measured by delayed-type hypersensitivity (DTH) is down-regulated by a cascade of antigen-specific T suppressor (Ts) cells . Recently, we have identified a population of CD4 T cells that up-regulate the anticryptococcal DTH response (Tamp cells) . The Tamp cells are found in the spleens of donor mice at 6 days after immunization with cryptococcal antigen, and they amplify the anticryptococcal DTH response when transferred to syngeneic recipients at the time of immunization of the recipients . In this study, we determined the effects of C . neoformans-specific Ts cells on the induction of the Tamp cells in the Tamp cell-donor mice and on the induction and expression of the amplified anticryptococcal DTH response in the Tamp cell-recipient mice . When cryptococcal-specific Ts1 cells were given at the time of immunization of the Tamp cell-donor mice, induction of Tamp cells was inhibited . In contrast, when Ts1 cells were given at the time of adoptive transfer of Tamp cells, the recipients displayed amplified DTH responses, indicating that Ts1 cells do not affect the Tamp cells' function once the Tamp cells have been produced . C . neoformans-specific Ts2 cells given at the time of either immunization or footpad challenge of the Tamp cell-recipient mice did not alter, to any measurable extent, the amplified DTH response . These results indicate that in addition to amplifying the anticryptococcal DTH response, Tamp cells may protect the anticryptococcal TDH cells from suppression by C . neoformans-specific Ts cells, much like contrasuppressor cells do in other systems . However, further characterization of the Tamp cells revealed that they are not adherent to Viscia villosa lectin, indicating that the anticryptococcal Tamp cells do not have this characteristic in common with contrasuppressor cells of other antigen systems.

Trans R Soc Trop Med Hyg, 1991 Jan-Feb, 85(1), 123 - 7
Murine monoclonal antibodies recognizing a non-capsular antigen that distinguishes between Cryptococcus neoformans var . neoformans and C . neoformans var . gattii; Hamilton AJ et al.; A panel of 4 monoclonal antibodies (mabs) of the IgG1 subclass have been made against a cytoplasmic antigen of Cryptococcus neoformans . Mab 4E2 recognized isolates of C . neoformans var . gatti by enzyme-linked immunosorbent assay (ELISA), whilst the other antibodies did not recognize these antigens . By Western blot 4E2 recognized determinants at 110-125, 65-70, 45-50 and 36-38 kDa . Mabs 9E6, 7C7 and 5D9 recognized bands at 36-38 and approximately 30 kDa . All 4 mabs (4E2, 9E6, 7C7 and 5D9) recognized both non-encapsulated and encapsulated isolates of C . neoformans var . neoformans by ELISA, and in addition showed reactivity to only the cytoplasm and cell membrane of yeasts by immunofluorescence . Mab 7C7 recognized antigens of the closely related fungus Trichosporon beigelii by ELISA but did not recognize any other fungal antigens . The other 3 mabs showed no recognition of T . beigelii or any other fungal pathogens tested.

J Med Vet Mycol, 1991, 29(1), 25 - 30
AIDS-associated cryptococcosis in Bujumbura, Burundi: an epidemiological study; Swinne D et al.; Cryptococcus neoformans var . neoformans was isolated from domestic dust in 54% of houses occupied or recently occupied by AIDS+ cryptococcosis patients and in 20% of control houses randomly chosen in Bujumbura, Burundi . It was not isolated from wards of similar patients in the University Hospital . This seems to prove that patients could not contaminate their own environment and that the presence of C . neoformans var . neoformans had another origin . In 40% of the cases, patients admitted contact with pigeons in the city and pigeon coops are frequently positive . We are convinced that the pigeon coops of the city play a part in the contamination of HIV+/AIDS patients; however, some patients denied any contact with pigeons and in these cases, the only possible source of contamination identified thus far is domestic dust, although the origin of the yeast remains unknownPIP: Researchers took 800 samples from the environment in Bujumbura, Burundi to examine the role of Cryptococcus neoformans var . neoformans in HIV positive/AIDS patients . Specifically they took 375 dust samples from 25 houses of 24 AIDS patients with cryptococcosis (1 patient had 2 homes) . 5 of the these patients lived in 1 area . So the researchers also took control samples from the same area . They also obtained contact plate samples from 10 internal medicine wards (4 with AIDS/Cryptococcosis patients, 2 AIDS patients who did not have cryptococcosis, and 4 vacant wards) in Kamenge University Hospital . The researchers isolated C . neoformans var . neoformans in the dust of 54% of the homes either occupied or recently occupied by the patients and in the dust of 20% of the control homes . Further 40% of the patients reported contact with pigeons . In fact, the researchers were able to sample the avian source of 25% (6) of all patients . They detected high doses of C . neoformans in 5 of the 6 pigeon coops . In those patients who did not report contact with pigeons, the researchers assumed these patients contracted cryptococcosis from spores in domestic dust . No spores were evident in the hospital wards including those with AIDS patients with cryptococcosis . Even though the researchers experiments with dissemination of spores did not reveal the extent of contamination they expected, they were sure that pigeon coops do play a contributory role in contaminating HIV positive and AIDS patients . Further they were concerned that AIDS patients who have received successful cryptococcosis treatment could be reinfected by returning to a home contaminated with dust harboring spores .

J Clin Lab Anal, 1991, 5(3), 168 - 74
Diagnostic value of lactate dehydrogenase isoenzymes in cerebrospinal fluid; Chatterley S et al.; To evaluate the diagnostic value of lactate dehydrogenase (LD) isoenzymes in cerebrospinal fluid (CSF), 93 consecutive CSF specimens were analyzed . These specimens were from patients of four categories: tumors, infections, hemorrhages, and others . It was found that the isoenzyme patterns overlapped among different categories, but they differed within each category and were thus helpful in differential diagnosis . For instance, metastatic tumors showed prominent LD-5, whereas a primary brain tumor demonstrated an increase in all fractions . Viral encephalitis revealed an increase in the first three isoenzymes and bacterial meningitis, the last two . In acquired immune deficiency syndrome (AIDS) cases, however, LD isoenzyme changes were demonstrated in CSF when only cryptococcal meningitis and not when encephalitis was present . Both subdural and subarachnoid hemorrhages showed elevation of all fractions in our study . Elevation of the first three fractions was usually due to brain tissue damage or hemorrhage, as proven by our isoenzyme study of hemolysate mixed with CSF . The prominence of the last two fractions was related to anaerobic metabolism in the central nervous system or to granulocytic infiltration . In conclusion, LD isoenzyme analysis in CSF is helpful in differential diagnosis of various CNS disorders, although its sensitivity awaits further improvement.

Rev Med Panama, 1991 Jan, 16(1), 50 - 6
{Pulmonary cryptococcosis}; Echavarria A et al.; The authors present the clinical history of a 61 year old woman who was treated in the Metropolitan Hospital Complex Arnulfo Arias Madrid of the Social Security . The patient had experienced weight loss, chills and pain in the left chest for a period of one month . The chest X-ray showed an irregular oval shaped pulmonary infiltrate, 5 x 5 cm, in the upper one third of the left lung field . Fiberoptic bronchoscopy revealed an endobronchial lesion in the superior division of the left upper lobe bronchus . Transbronchial biopsy and bronchial brushings showed Crytpcoccus neoformans . Clinical evaluations did not reveal involvement of the central nervous system, the immunological system or evidence of neoplastic disease . The patient was treated with Amphotericin B and Ketoconazole resulting in a complete cure . Amphotericin B was used on an ambulatory basis for the first time in their institution and in Panama.

J Comp Pathol, 1991 Jan, 104(1), 117 - 20
Concurrent systemic cryptococcosis and haemangiosarcoma in a dog; Kock ND et al.; A young dog with progressive neurological signs was humanely killed by the injection of barbiturate for postmortem examination . Lesions in the nose, lung, pancreas, lymph nodes, kidneys and the meninges were heavily infiltrated with Cryptococcus neoformans . In addition, haemangiosarcoma was detected in the right atrium . The finding of systemic mycosis and neoplasia together in a young dog suggests an immunosuppressed state.

Rev Infect Dis, 1991 Jan-Feb, 13(1), 64 - 7
Manifestations of pulmonary cryptococcosis in patients with acquired immunodeficiency syndrome; Cameron ML et al.; Cryptococcosis is a common opportunistic infection in patients with AIDS . Meningitis is the most frequent manifestation of infection with Cryptococcus neoformans; pneumonia due to this organism, though less frequently recognized, is also a significant entity . A retrospective review was performed of all patients seen at Duke University Medical Center between January 1981 and July 1989 who were infected with both human immunodeficiency virus type 1 and C . neoformans . Of 31 patients with these concomitant infections, 12 had cryptococcal pneumonia (10 definite and two presumptive cases) . Eleven of these 12 patients had evidence of extrapulmonary cryptococcal disease as well . Chest radiography showed interstitial infiltrates in 11 instances . For ten of the 12 patients, pulmonary cultures were positive for C . neoformans . Bronchoalveolar lavage fluid from all five patients who underwent bronchoscopy yielded the organism . Acute-phase mortality from cryptococcosis was 42% among patients with pneumonia . Cryptococcal pneumonia in patients with AIDS is probably more common than has previously been recognized and typically presents as interstitial disease that may mimic other opportunistic infections.

Dermatologica, 1991, 182(1), 7 - 11
Variant of hyper-IgE syndrome: the differentiation from atopic dermatitis is important because of treatment and prognosis; Hochreutener H et al.; The hyper-IgE syndrome is characterized clinically by recurrent staphylococcal abscesses of the skin, lungs and other sites from infancy . Affected patients also have a pruritic dermatitis that differs in character and distribution from lesions of atopic dermatitis . Most lack other signs of atopic disease, develop persistent pneumatoceles and have osteopenia . Laboratory abnormalities include the consistent presence of marked hyperimmunoglobulinemia E and eosinophilia of blood, sputum and tissues . They may have other inconsistent abnormalities of humoral and cellular immune responses and sometimes of phagocytic cell chemotactic responsiveness . Other clinical problems reported in such patients have included lymphomas, cryptococcal meningitis and cutaneous fungal disease . An 18-year-old male patient with a variant of the hyper-IgE syndrome, which he had acquired after a measles attack at the age of 5 years, suffered from recurrent ulcerative dermatitis and lymph node abscesses . Immunological investigation revealed an excessively elevated total serum IgE level (46,850 IU/ml), the presence of specific IgE to staphylococci, and quantitative and functional deficiency of IgG2 . Skin and serological (radioallergosorbent) tests to inhalant and nutritive allergens were negative . Differentiation from atopic dermatitis should be made, because a long-term antistaphylococcal regime not only improves skin lesions but hinders the occurrence of lung abscesses and pneumatoceles.

J Clin Microbiol, 1991 Jan, 29(1), 192 - 6
Demonstration of a cell wall antigen cross-reacting with cryptococcal polysaccharide in experimental disseminated trichosporonosis; Melcher GP et al.; Patients with disseminated infections caused by Trichosporon beigelii have a circulating antigen that cross-reacts with the polysaccharide capsule of Cryptococcus neoformans . We studied the localization of this antigen by immunoelectron microscopy in a rabbit model of experimental disseminated trichosporonosis . Deparaffinized lung sections were examined by using a murine monoclonal anti-cryptococcal polysaccharide antibody and colloidal gold particles coated with goat antibody to murine immunoglobulin G . Antigen that cross-reacted with the monoclonal antibody was observed in the T . beigelii cell wall and in a fibrillar matrix extending from the cell wall.

Infect Immun, 1991 Jan, 59(1), 59 - 64
Facilitated isolation, purification, and analysis of glucuronoxylomannan of Cryptococcus neoformans; Cherniak R et al.; Cryptococcus neoformans was cultured in a chemically defined medium . The culture was adjusted to 0.25% formaldehyde or autoclaved after 5 days of growth at 35 degrees C, and a cell-free supernatant was obtained by centrifugation . Solid calcium acetate was added to the supernatant to give a 5% solution, and the pH was adjusted to approximately 5 with glacial acetic acid . The polysaccharide (PS) was precipitated by the addition of 3 volumes of 95% ethanol . The PS was dissolved in 0.2 M NaCl, and insoluble calcium salts were solubilized by the addition of several drops of glacial acetic acid . The PS solution was treated by ultrasonic irradiation for 15 min . This concurrently decreased the molecular weight of the PS and reduced the viscosity of the solution . The ultrasonically irradiated PS was precipitated by differential complexation with hexadecyltrimethylammonium bromide at 23 degrees C, the complex was dissolved in 1 M NaCl, and the glucuronoxylomannan was precipitated by adding 3 volumes of ethanol . The glucuronoxylomannan was dissolved in 1 M NaCl and then ultrasonically irradiated for 2 h to reduce the molecular mass to a limiting value of approximately 100 kDa (GXMS) . The purified GXMS was centrifuged, dialyzed, and finally recovered by lyophilization . GXMS was chromatographed on DEAE-cellulose at reasonable concentrations without the complication of high solution viscosity . The sugar composition and structure of GXMS were determined by gas-liquid chromatography, permethylation gas-liquid chromatography-mass spectrometry, and 13C nuclear magnetic resonance spectroscopy . The improved solution characteristics of GXMS were ideal for the determination of its chemical and serological properties.

Infect Immun, 1991 Jan, 59(1), 24 - 8
Killing of Cryptococcus neoformans strains by human neutrophils and monocytes; Miller MF et al.; The susceptibility of various strains of Cryptococcus neoformans to killing by human polymorphonuclear leukocytes (PMNs) and monocytes was investigated . Five previously characterized strains of C . neoformans serotype A, a capsule-free mutant, and six recent clinical isolates were compared . PMNs and monocytes were isolated from normal peripheral blood and allowed to adhere to the flat-bottom wells of microtiter plates . Yeast cells of C . neoformans were added in the presence of normal human serum, and the plates were incubated at 37 degrees C . After 4 h, killing was determined by comparing the quantitative plate counts of viable yeast cells in experimental wells with counts in control wells containing yeast cells in the absence of leukocytes . No appreciable growth of yeast cells occurred in the wells during the incubation period . Both PMNs and monocytes effectively killed yeast cells at effector-to-target ratios as low as 1:1, although monocytes failed to kill the capsule-free strain 602 at a 1:1 ratio . With 9 of 12 strains, PMNs killed C . neoformans more effectively than did monocytes . Significant interstrain variation in killing occurred for both monocytes and PMNs, and the recent, clinical isolates were more resistant to killing by monocytes and PMNs than were the previously characterized strains . The extent to which different strains were killed by monocytes and PMNs was not consistently related to the size of the capsule or the entire cell . Normal PMNs and monocytes are remarkably effective in killing strains of C . neoformans in the absence of specific antibody and appear to constitute a significant defense mechanism in the peripheral circulation.

Am J Gastroenterol, 1991 Jan, 86(1), 1 - 15
Hepatobiliary manifestations of the acquired immune deficiency syndrome; Cappell MS; Patients with the acquired immune deficiency syndrome (AIDS) frequently develop hepatic dysfunction . Although hepatic injury may indirectly result from malnutrition, hypotension, administered medications, sepsis, or other conditions, the hepatic injury is frequently due to opportunistic hepatic infection, directly related to AIDS . Infection with Mycobacterium avium intracellulare typically occurs in patients with advanced immunocompromise and with systemic symptoms due to widely disseminated infection . In contrast, hepatic tuberculosis often occurs with less advanced immunocompromise . Cytomegaloviral infection may produce a hepatitis . Cytomegaloviral and cryptosporidial infections have been implicated as causes of acalculous cholecystitis and of a secondary sclerosing cholangitis . About 10-20% of patients with AIDS have chronic hepatitis B infection . These patients tend to develop minimal hepatic inflammation and necrosis . The clinical findings in patients with hepatic cryptococcal infection are usually due to concomitant extrahepatic infection . Hepatic histoplasmosis usually develops as part of a widely disseminated infection with systemic symptoms . Hepatic involvement by Kaposi's sarcoma is rarely documented ante mortem because an unguided liver biopsy is an insensitive diagnostic procedure . Patients with non-Hodgkin's lymphoma of the liver typically have lymphadenopathy, hepatomegaly, and systemic symptoms . As a pragmatic approach, patients with liver dysfunction and HIV-related disease should have a sonographic or computerized tomographic examination of the liver . Patients with dilated bile ducts should undergo endoscopic retrograde cholangiopancreatography because opportunistic infection may produce biliary obstruction . Patients with a focal hepatic lesion should be considered for a guided liver biopsy . Patients with a significantly elevated serum alkaline phosphatase level should be considered for a percutaneous liver biopsy . When performed for these indications, liver biopsy will demonstrate a significant disease involving the liver in about 50% of patients with AIDS and in about 25% of patients who are HIV seropositive but who are not known to have AIDS . The clinical impact of a diagnostic biopsy is blunted by a lack of efficacious therapy for many opportunistic infections.

Ann Pathol, 1991, 11(4), 236 - 47
{Neuropathologic study of 135 adult cases of acquired immunodeficiency syndrome (AIDS)}; Gray F et al.; The central nervous system was examined in 135 adult AIDS patients who died between August 1982 and December 1990 . Twenty two brains showed non-diagnostic changes including microglial nodules, discrete myelin pallor with reactive astrocytosis, mineralization of blood vessels and granular ependymitis . In 105 brains with specific changes, toxoplasmosis was the most frequent finding (55 cases) manifested by multifocal necrotic lesions or diffuse pseudo-encephalitic process . Other opportunists included cytomegalovirus (21 case), progressive multifocal leukoencephalopathy (1 cases), cryptococcosis (6 cases), mycobacterium avium intracellulaire (2 cases), varicella-zoster virus (2 cases), aspergillosis (1 case) and multiple bacterial microabscesses (1 case) . Multinucleated giant cells were found in 52 cases . In 40 cases, they were widely disseminated throughout the brain and in 39 cases, they were associated with diffuse or multifocal white matter changes . Fifteen cases had a cerebral lymphoma, 9 hepatic encephalopathy, 1 centropontine myelinolysis and 1 focal pontine leukoencephalopathy . Three cases had a cerebral haemorrhage due to disseminated intravascular coagulation, antithrombin therapy and amyloid angiopathy . Spinal changes in 13 cases included vacuolar myelopathy (7 cases), HIV myelitis (1 case) and ganglio-radiculitis (1 cases), cytomegalovirus myelo-radiculitis (1 case) secondary spread from a lymphoma (1 case) and spinal infarcts due to disseminated intravascular coagulation (1 case) . These lesions were frequently atypical and various combinations of all these pathologies were encountered in the same brain, sometimes in the same area and occasionally in the same cell . Chronological variations in the incidence of some complications could be related to changes in treatment.

Diagn Cytopathol, 1991, 7(5), 536 - 9
Primary diagnosis of disseminated fungal disease by fine-needle aspiration of soft-tissue lesions; Sherman ME et al.; Two cases of disseminated fungal infections diagnosed by fine-needle aspiration of soft-tissue masses are presented . Both patients were initially treated on an outpatient basis for a presumed musculoskeletal disorder before the diagnostic biopsy was obtained . The first patient apparently contracted Coccidioides immitis infection while residing in Arizona, but the diagnosis was rendered on an aspirate of a buttock mass performed in Boston . The second patient, a non-insulin-dependent diabetic, was diagnosed with a cryptococcal abscess on an aspirate of a shoulder mass performed in the emergency room . The diagnosis of coccidioidomycosis was confirmed by culture and that of Cryptococcus by serology . Fungal infection was clinically unsuspected in both patients and the cytologic diagnosis facilitated rapid implementation of therapy.

Diagn Cytopathol, 1991, 7(5), 508 - 12
Granulomatous prostatitis: a spectrum including nonspecific, infectious, and spindle cell lesions; Stanley MW et al.; Most granulomas of the prostate are nonspecific; infectious, post-operative, and allergic lesions are much less common . Fine-needle aspiration findings in the typical case are distinctive and easily recognized . Several series have been reported, but few have included histologic follow-up . We describe three cases of granulomatous prostatitis (GP) which showed a spectrum of findings confirmed by histologic sections . In all cases, carcinoma was suspected clinically . Case 1 represents typical nonspecific GP with epithelioid and multinucleated histiocytes . In case 2, aggregates of epithelioid histiocytes alternated with areas of necrosis and neutrophils . Histologically, the granulomas showed purulent centers . Silver stains revealed budding yeast in smears and sections . Cultures of FNA material subsequently revealed Cryptococcus . In case 3, the histiocytes were predominantly spindled and occurred singly and in groups . The differential diagnosis included reactive and neoplastic spindle cell lesions . Histologic sections showed GP with spindled histiocytes . Appreciation of the broad cytologic spectrum of GP will facilitate accurate cytologic diagnosis.

Diagn Cytopathol, 1991, 7(4), 415 - 6
Cryptococcal thyroiditis: report of a case diagnosed by fine-needle aspiration cytology; Vaidya KP et al.; A 54-yr-old female diabetic presented with a febrile illness and respiratory distress associated with bilateral alveolar infiltration . The left lobe of the thyroid gland was enlarged and failed to concentrate pertechnetate . The patient was euthyroid . Cryptococcus neoformans was recognized in a fine-needle aspirate and was confirmed by culture; it was also grown in blood culture . Death was attributed to the respiratory condition . This report emphasizes the emergence of mycotic infections of the thyroid and presents an efficient method for their identification.

Biol Met, 1991, 4(3), 141 - 3
Novel broad-spectrum metal-based antifungal agents . Correlations amongst the structural and biological properties of copper (II) 2-acetylpyridine N4-dialkylthiosemicarbazones; Kumbhar AS et al.; Copper(II) complexes of the type {Cu(L)X}, where L = tridentate anion of 2-acetylpyridine N4-diethyl thiosemicarbazone and X = C1 or Br, were screened against seven fungal strains pathogenic to man viz . Aspergillus niger, Aspergillus fumigatus, Candida albicans, Cryptococcus neoformans, Tricophyton rubrum, Epidermophyton floccosum and Microsporum canis . The greater growth inhibition exhibited by the bromo complex can be explained on the basis of its lower Cu(II)/Cu(I) redox couple and greater covalent bonding . These compounds represent a novel class of metal-based antifungal agents which provide opportunities for a large number of synthetic variations for modulation of the activities.

Mycoses, 1991 Jan-Feb, 34(1-2), 63 - 5
Cryptococcal meningoencephalitis in a patient with Hodgkin's lymphoma: successful treatment with fluconazole; Bolignano G et al.; The authors report a case of cryptococcal meningoencephalitis in a 22-year-old male with Hodgkin's disease at third stage B . Cryptococcus neoformans was isolated from cerebral spinal fluid (CSF) and blood specimens . Latex antigen agglutination tests and India ink preparations also were positive for this pathogenic yeast . Drug treatment for a week with 20 mg i.v./day of amphotericin B in combination with 2.5 g i.v./day of 5-fluorocytosine did not lead to any improvement in the patient . The patient became asymptomatic after the first week of treatment with a daily dose of 400 mg of fluconazole, administered intravenously . After two months of this regimen, all laboratory tests on CSF and blood specimens were negative.

J Med Vet Mycol, 1991, 29(2), 121 - 4
Temperature regulation of the cryptococcal phenoloxidase; Jacobson ES et al.; Melanin formation at 37 degrees C has been proposed as a virulence factor in Cryptococcus neoformans . However, whereas catecholamine uptake is maintained at this temperature, phenoloxidase, which catalyses the oxidation of catecholamine to melanin, is severely decreased in most wild type strains cultivated at 37 degrees C.

Ann Pathol, 1991, 11(3), 169 - 75
{Intestinal microsporidiosis . 3 cases in HIV seropositive patients}; Michiels JF et al.; Three cases of intestinal microsporidiosis are reported, in acquired immunodeficiency syndrome patients, with a chronic diarrhea . The first case is associated with an intestinal cryptococcosis and with a cytomegalovirus infection and the second case was diagnosed on ileal biopsy specimen . Since the first description of Enterocytozoon bieneusi in 1985 . 49 cases of intestinal microsporidiosis are reported in the literature, all in AIDS patients and the frequency of this infection is probably underrated . Prospective studies find it in 6 to 30% of cases . This parasite must be suspected in HIV seropositive patients with clinically chronic unexplained diarrhea or with intestinal atrophy.

J Bacteriol, 1991 Jan, 173(1), 401 - 3
Catecholamine uptake, melanization, and oxygen toxicity in Cryptococcus neoformans; Jacobson ES et al.; Oxygen sensitivity mutations of Cryptococcus neoformans were mapped to three genetic loci . Three oxygen-sensitive mutants had mutations that appeared allelic and exhibited albinism tightly linked to oxygen sensitivity; these three and a fourth exhibited defects in catechol uptake and catechol oxidation to melanin . Catecholamine metabolism appears to protect C . neoformans from oxidants.

Microbiol Immunol, 1991, 35(2), 125 - 38
Comparison of serological and chemical characteristics of capsular polysaccharides of Cryptococcus neoformans var . neoformans serotype A and Cryptococcus albidus var . albidus; Ikeda R et al.; The antigenic formula and chemical structure of capsular polysaccharide (CPS) of Cryptococcus albidus var . albidus (C . albidus) were studied in relation to those of C . neoformans var . neoformans serotype A (C . neoformans A) . The results of slide agglutination tests with factor sera and reciprocal adsorption experiments showed that antigenic formula of C . albidus was the same as that of C . neoformans A . The soluble CPSs from the two species were obtained from culture supernatants by precipitation with ethanol followed by purification by chromatography on DEAE-cellulose column . The structural analyses of such CPSs from the two species showed that the antigenic CPS fractions consisted of a backbone of alpha(1-3)-linked D-mannopyranosyl residues with a single branch of beta(1-2)-xylose or glucuronic acid, and mostly with O-acetyl groups, in which side chains and O-acetyl groups were responsible for antigenic specificity . It was found that there was a minor difference between the CPS of C . neoformans A and that of C . albidus; in the former, unsubstituted mannose residues existed in a low frequency, but in the latter none . Moreover, the 1H-nuclear magnetic resonance spectra of partially hydrolyzed acidic fragments of the two CPSs indicated that two xylose side chains were present between glucuronic acid side chains . Taken together, it was suggested that these two species of C . neoformans A and C . albidus are closely related to each other in their CPSs.

J Gen Intern Med, 1991 Jan-Feb, 6(1 Suppl), S24 - 31
Neurologic and psychiatric manifestations of HIV disease; Hollander H; Neuropsychiatric problems have assumed an increasingly prominent role in HIV-infected individuals . Disease occurs at all levels of the central and peripheral nervous systems by a variety of mechanisms . The AIDS dementia complex is the prototypical example of "direct" effects of HIV on the neuraxis, while infections such as toxoplasmosis and cryptococcal meningitis are complications of HIV-induced immunosuppression . Neurologic manifestations vary in frequency depending upon the overall stage of HIV disease; diagnostic difficulties may be encountered because of HIV's effect on cerebrospinal fluid parameters . The uncertainties of management of neurosyphilis in this setting provide and example of these problems . As is the case with other organ systems, the main goal of neurodiagnostic efforts is to find the increasing number of treatable components of neuropsychiatric dysfunction.

J Med Vet Mycol, 1991, 29(2), 125 - 8
Inhibition of I-A expression in rat peritoneal macrophages due to T-suppressor cells induced by Cryptococcus neoformans; Masih DT et al.; The expression of I-A antigen in rat peritoneal cells was significantly reduced during infection with Cryptococcus neoformans . When studying the in vitro action of T-suppressor cells induced by the fungus, or a soluble factor from the T-suppressor cells, a significant decrease in I-A expression by the peritoneal cells was observed . This expression was partially restored by indomethacin.

Scand J Infect Dis, 1991, 23(6), 697 - 702
Low yield of screening for cryptococcal antigen by latex agglutination assay on serum and cerebrospinal fluid from Danish patients with AIDS or ARC; Hoffmann S et al.; From July 1, 1989 to September 5, 1990, 530 serum specimens and 50 cerebrospinal fluid (CSF) specimens from 334 HIV-1 infected patients, most of whom had AIDS or ARC, were analysed in a cryptococcal antigen latex agglutination assay, and all were negative . Three cases of meningitis due to Cryptococcus neoformans diagnosed by microscopy and culture in 3 HIV-1 infected patients are presented . Stored specimens of serum and CSF from these patients were assayed for cryptococcal antigen, and in all 3 the onset of meningitis was preceded by the presence of cryptococcal antigen in serum . It is concluded that the low occurrence of cryptococcosis in our patient population does not justify a routine serum screening for cryptococcal antigen.

Rev Mal Respir, 1991, 8(6), 583 - 6
{A predominant manifestation of pleural cryptococcosis in acquired immunodeficiency syndrome}; Bayle JY et al.; Systemic cryptococcosis occurs in at least 6% patients with human immunodeficiency virus infection (HIV) . The lung infection by cryptococcus neoformans, less frequently observed than meningeal involvement, consists usually in focal parenchymal mycosis . Authors report an apparently isolated pleural cryptococcosis in a 41 years old mal with HIV infection . Diagnosis was performed initially by pleural and bronchial alveolar lavage (BAL) fluid culture . Characteristic cryptococcosis pathological and histologic findings from thoracoscopy and open pleural biopsy are described . Cryptococcus capsular polysaccharides stainings and thoracoscopy interests are emphasized.

Ann Fr Anesth Reanim, 1991, 10(5), 463 - 7
{Cerebral aspergillosis in immunocompromised patients}; Preckel MP et al.; Three cases of central nervous system (CNS) aspergillosis in immunocompromised patients are reported . All three had neurological symptoms with normal cerebrospinal fluid (CSF) . The CT scan showed poorly defined low density lesions which were not enhanced by contrast medium . They also had pulmonary signs and fever despite antibiotic treatment . Aspergillus fumigatus was isolated from bronchoalveolar lavage fluid . Antifungal therapy was started promptly, associating amphotericin B, itraconazole and flucytosine . Unfortunately, they died within 2 days to 2 weeks after admission in the intensive care unit . Postmortem examinations revealed disseminated aspergillosis with colonization of brain, lung, heart and kidney . The CT scan signs were quite different from those seen with the more usual bacterial ring lesions . In immunocompromised patients, the agents responsible for producing these findings are Aspergillus, Nocardia, Cryptococcus, Toxoplasma and Mycobacterium tuberculosis . Signs involving organs other than the CNS, and an examination of the CSF, should provide elements for establishing a differential diagnosis . Early antifungal treatment is the only chance of survival . Recrudescent fever and pulmonary signs occurring in neutropenic patients after antibacterial antibiotic treatment has been started are sufficient criteria for empirically starting amphotericin B administration unless clinical judgement dictates otherwise.

Neuroradiology, 1991, 33(5), 443 - 6
Gd-DTPA-enhanced MR imaging of cryptococcal meningoencephalitis; Takasu A et al.; This report describes magnetic resonance (MR) imaging of biopsy-proved cryptococcal central nervous system (CNS) infection in a 31-year-old HIV negative man . Initial MR imaging revealed multi-focal Gd-DTPA enhancement and showed more lesions than contrast enhanced CT . The lesions regressed after antifungal therapy . MR imaging aids in diagnosis as well as helps to monitor the response to the pharmacological therapy of cryptococcal meningoencephalitis and possibly provides valuable insights into the pathophysiology of this condition.

Nephrol Dial Transplant, 1991, 6(9), 649 - 55
Ocular complications in renal allograft recipients; Das T et al.; Ocular complications in renal allograft recipients are a significant cause of morbidity . Of 80 renal transplant recipients, 42 (52.5%) developed ocular complications . These included posterior subcapsular cataract in 22 patients (27.5%), opportunistic ocular infections by CMV, cryptococcus, mucormycosis, herpes simplex and herpes zoster in five (6.25%), steroid-induced raised intraocular pressure in four (5%) and primary disease-related vascular complications in ten (12.5%) . Our findings highlight the importance of regular ocular examination of all allograft recipients in the post-transplant period.

Diagn Cytopathol, 1991, 7(1), 88 - 91
Fine-needle aspiration cytology of adrenal cryptococcosis: a case report; Powers CN et al.; A case of adrenal cryptococcosis diagnosed by fine-needle aspiration biopsy cytology in a 58-yr-old man is presented . The organisms were easily seen with routine modified Wright stain (Diff-Quik) as variably sized yeasts, some with a brightly eosinophilic capsule . The diagnosis was confirmed with mucicarmine and silver stains . The identification of fungi with routine cytologic stains allows a rapid presumptive diagnosis of the infectious agent, collection of material for confirmatory special stains, and prompt initiation of therapy.

Rev Pneumol Clin, 1991, 47(3), 133 - 6
{Pleuropulmonary cryptococcosis disclosing AIDS}; Zalcman G et al.; The authors report a case of AIDS revealed by pleuropulmonary cryptococcosis . The infection was diagnosed by culture of the pleural fluid and confirmed by microscopic examination of the cerebrospinal fluid, using Indian ink as stain . Apyrexia and return to normal of chest radiography were obtained with oral fluconazole . Twelve months after this episode the patient is alive and had no relapse under maintenance treatment with this drug.

J Acquir Immune Defic Syndr, 1991, 4(8), 770 - 6
Predictive value of CD4 lymphocyte numbers for the development of opportunistic infections and malignancies in HIV-infected persons; Crowe SM et al.; Infection with the human immunodeficiency virus (HIV) results in progressive depletion of the CD4 subset T-lymphocytes and the development of opportunistic infections and certain malignancies . Charts were reviewed for 185 HIV-infected individuals with 265 AIDS-defining illnesses (ADIs) who had T-lymphocyte subset analyses performed within 2 months prior to or 1 month following the diagnosis . Also included were 22 HIV-infected patients with oral candidiasis and 20 with asymptomatic infection . Significant differences in CD4 lymphocyte numbers were observed between the 12 ADIs, oral candidiasis, and asymptomatic infection, allowing them to be grouped into five general categories, based on mean CD4 count: (a) asymptomatic infection, CD4 greater than 500/mm3; (b) oral candidiasis and tuberculosis, range 250-500/mm3; (c) Kaposi's sarcoma, lymphoma, and cryptosporidiosis, range 150-200/mm3; (d) Pneumocystis carinii pneumonitis, disseminated Mycobacterium avium complex, herpes simplex ulceration, toxoplasmosis, cryptococcosis, and esophageal candidiasis, range 75-125/mm3; (e) cytomegalovirus retinitis, less than 50/mm3 . Our data concur with clinical impressions and provide a basis for interim treatment and prophylaxis recommendations.

Pediatrie (Bucur), 1991, 40(1-2), 69 - 83
{Pneumocystis carinii pneumonia}; Dragomir D et al.; The paper reports on a theme of important pediatric interest, pneumonia with Pneumocystis carinii (PC), a more widespread affection lately, due to the progress in pediatric reanimation, on the one hand (that allowed the survival for a long time of several biologically handicapped infants) and as a consequence of the more and more common use of immunosuppressing therapy, on the other hand (malignant diseases, transplant of organs, etc.); another important role in the increase of the PC pneumonia is played, recently, both in the adult and the child, by the infection with HIV (acquired immunodeficiency syndrome) . The authors discuss largely on the pathogenic agent, PC, proved to be a fungus by molecular genetic studies, and on the biological field (small age, dystrophy, prematurity, "debilitating" chronic diseases, long diarrheic diseases, congenital malformations, hospitalization, some infections with long evolution: tuberculosis, Cryptococcus, infection with cytomegalic virus) . The paper also deals with epidemiology, pathogeny and pathologic anatomy of the disease (characteristic macroscopic aspect: nonaired lung of high consistency, with whitish infiltrations alternating with congestive zones and the microscopic aspect of alveolo-interstitial pneumonia) . The clinical picture includes the common form, met in the biologically handicapped infant and hypoergic hypoimmune form, appearing in all ages in immunodeficient subjects . Radiological examination, pulmonary scintigraphy and a series of laboratory data (with evidence of parasitic cysts) complete the clinical examination, making easier the diagnosis . The techniques of seroimmunological diagnosis offers great hope for the future . The positive diagnosis shows the clinical elements that suggest the presence of the disease, the contribution of the radiologic examination and mainly the presence of the parasite in the bronchitic secretions; the therapeutic response is a retroactive element in the positive diagnosis . The differential diagnosis is presented in detail . The paper concludes with a series of treatment schemes used, prophylaxis, evolution, complications and prognosis of the disease.

Clin Neurol Neurosurg, 1991, 93(3), 257 - 8
Treatment of impaired consciousness with lumbar punctures in a patient with cryptococcal meningitis and AIDS; van Gemert HM et al.; A 50 year old man with AIDS, cryptococcal meningitis and a normal CT-scan developed impaired consciousness and even deep coma associated with very high CSF pressure . After lumbar CSF drainage consciousness improved dramatically . We conclude that in patients with cryptococcal meningitis who have impaired consciousness and a normal CT scan, CSF drainage to improve the level of consciousness should be considered.

Nippon Juigaku Zasshi, 1990 Dec, 52(6), 1171 - 4
Isolation of saprophytic Cryptococcus neoformans; Pal M et al.; Isolation of Cryptococcus neoformans was carried out on sunflower seed agar medium (SFA) and Sabouraud dextrose agar (SDA) . Out of 346 environmental substrates (133 fruits, 107 avian extreta, 91 vegetables and 15 wooden scrapings) tested, 3 specimens were positive for C . neoformans . The positive isolations came from the fruits of 2 banana (Musa sapientum) and a potato tuber (Solnum tuberosum) . The pathogen could not be demonstrated in 107 samples of avian droppings and 15 of wooden materials . All the 3 isolates of the yeast were obtained on SFA, while they were not cultured on the plates of SDA with chloramphenicol which were badly contaminated with rapidly growing molds, yeasts and bacteria . To the present author's knowledge, this appears to be the first reports of the isolation of this pathogenic basidiomycetous yeast from contaminated fruits of banana . We suggest more comprehensive ecological surveys to search for environmental niche of C . neoformans var . neoformans and C . neoformans var . gattii as the latter variety is also implicated in the etiology of cryptococcosis.

Infect Dis Clin North Am, 1990 Dec, 4(4), 789 - 808
Fungal meningitis; Treseler CB et al.; Fungal meningitis tends to be a subacute or chronic process; however, it may be just as lethal as bacterial meningitis if untreated . There are many similarities between the pathogenic fungi . Most of the fungi are aerosolized and inhaled, and initiate a primary pulmonary infection which is usually self-limited . Hematogenous dissemination may follow the initial infection, with subsequent involvement of the CNS . Rarely, trauma or local extension provides the route to CNS infection . The host is frequently, although not always, immunosuppressed . The hyphae of molds generally cause focal disease with hemorrhagic necrosis secondary to vascular thrombosis . The yeasts tend to cause a more diffuse process with the base of the brain being primarily affected, such that hydrocephalus is seen as a frequent complication of chronic disease . Diagnosis may be difficult, as the CSF may be normal, with negative smears and sterile cultures, although more often there is at least one abnormality indicating disease . Serologies (if available, depending on the fungus) may point towards the proper diagnosis, as may a careful travel history . Currently, amphotericin B is still the drug of choice in most situations; however, the newer azole antifungal agents offer great promise, especially in the treatment of cryptococcal meningitis . The precise role of such agents will remain unclear until appropriate large-scale studies of their effectiveness have been completed . The treatment of the unusual CNS mycoses will continue to be based on clinical experience, and reports of the use of new azoles in these diseases need to be critically evaluated.

Infect Dis Clin North Am, 1990 Dec, 4(4), 583 - 98
Approach to diagnosis of meningitis . Cerebrospinal fluid evaluation; Greenlee JE; CSF evaluation is the single most important aspect of the laboratory diagnosis of meningitis . Analysis of the CSF abnormalities produced by bacterial, mycobacterial, and fungal infections may greatly facilitate diagnosis and direct initial therapy . Basic studies of CSF that should be performed in all patients with meningitis include measurement of pressure, cell count and white cell differential; determination of glucose and protein levels; Gram's stain; and culture . In bacterial meningitis, Limulus lysate assay and tests to identify bacterial antigens may allow rapid diagnosis . Where there is strong suspicion of tuberculous or fungal meningitis, CSF should also be submitted for acid-fast stain, India ink preparation, and cryptococcal antigen; unless contraindicated by increased intracranial pressure, large volumes (up to 40-50 mL) should be obtained for culture . If a history of residence in the Southwest is elicited, complement-fixing antibodies to Coccidioides immitis should also be ordered . Newer tests based on immunologic methods or gene amplification techniques hold great promise for diagnosis of infections caused by organisms that are difficult to culture or present in small numbers . Despite the great value of lumbar puncture in the diagnosis of meningitis, injudicious use of the procedure may result in death from brain herniation . Lumbar puncture should be avoided if focal neurologic findings suggest concomitant mass lesion, as in brain abscess, and lumbar puncture should be approached with great caution if meningitis is accompanied by evidence of significant intracranial hypertension . Institution of antibiotic therapy for suspected meningitis should not be delayed while neuroradiologic studies are obtained to exclude abscess or while measures are instituted to reduce intracranial pressure.

Infect Dis Clin North Am, 1990 Dec, 4(4), 555 - 81
Pathogenesis and pathophysiology of meningitis; Tunkel AR et al.; Advances in the understanding of the pathogenesis and pathophysiology of meningitis have occurred primarily through the use of experimental animal models . These models have proven to be particularly valuable in experimental bacterial meningitis, focusing on the bacterial virulence factors responsible for the initiation of infections, CNS invasion, and induction of SAS inflammation . Recent studies have examined the formation of host inflammatory cytokines in response to these virulence factors . These cytokines may be responsible for many of the pathophysiologic consequences of bacterial meningitis (eg . increased BBB permeability, cerebral edema, and increased intracranial pressure) . Meningitis due to C . neoformans occurs most commonly in patients with defects in cell-mediated immunity (eg, AIDS), and the depletion of T helper cells in AIDS patients may allow unrestricted cryptococcal growth . Viral meningitis is an illness of low prevalence when compared with the overall occurrence of viral infections at other sites . CNS infection usually occurs by means of traversal across barriers that normally exclude viral invasion of the CNS, primarily through hematogenous dissemination from initial sites of infection . These advances in the pathogenesis and pathophysiology of bacterial, fungal, and viral meningitis may lead to the development of innovative treatment strategies for these disorders.

Am Rev Respir Dis, 1990 Dec, 142(6 Pt 1), 1313 - 9
Human alveolar and peritoneal macrophages mediate fungistasis independently of L-arginine oxidation to nitrite or nitrate; Cameron ML et al.; Human alveolar macrophages (HAM) from 28 normal volunteers were found to inhibit replication of Cryptococcus neoformans . Conditions under which fungistasis occurred were different than those required for mouse peritoneal macrophage-mediated fungistasis . Inhibition of fungal replication by mouse peritoneal macrophages (MPM) requires that the macrophages are activated and that the cocultures of C . neoformans and macrophages be done in the presence of serum, L-arginine, and endotoxin . During MPM-mediated fungistasis and tumor cell killing, L-arginine is oxidized to NO2-, NO3-, and L-citrulline . In addition, MPM have arginase activity that converts L-arginine to L-ornithine and urea . HAM-mediated fungistasis was similar to that mediated by MPM in terms of the serum requirement, but HAM did not require L-arginine or endotoxin . HAM did not produce NO2- or NO3- detectable by colorimetric and bioassay, nor did HAM produce L-citrulline or L-ornithine from 14C-radiolabeled L-arginine as detectable by reverse-phase ion-pairing HPLC of macrophage-C . neoformans coculture supernatants . HAM had no detectable arginase activity, hence there was no evidence for L-arginine nitrogen metabolism in HAM . HAM-mediated fungistasis was not enhanced by endotoxin or by recombinant human interferon-gamma (rHIFN-gamma) . The combination of endotoxin and rHIFN-gamma inhibited the fungistatic effect of HAM . Human peritoneal macrophages (HPM) from women undergoing laparoscopy were tested for fungistasis and L-arginine nitrogen oxidation . Partial inhibition of cryptococcal replication occurred; however, there was no evidence of L-arginine metabolism to NO2- or NO3-.(ABSTRACT TRUNCATED AT 250 WORDS)

Eur J Epidemiol, 1990 Dec, 6(4), 398 - 403
Epidemiological and clinical aspects of mycoses in patients with AIDS-related pathologies; Morace G et al.; Mycological, cultural and/or serological studies were performed on 98 patients hospitalized in the Department of Infectious Diseases of the Catholic University in Rome with diagnoses of acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC) diseases . The incidence of mycoses was evaluated by retrospectively analyzing the results of mycological examinations and comparing them with clinical manifestations . The presence of concomitant bacterial, viral and parasitic infections was also examined . For epidemiological purposes, the study was extended to include the biotyping of all yeasts isolated from patients hospitalized between September 1988 and February 1989 in the same Department . Antimycotic susceptibility was also determined for the first yeast isolate obtained from each of these patients . Oral candidiasis (50 cases) caused by Candida albicans was the most frequent mycosis, followed by esophageal candidiasis (13 cases) and cryptococcosis (6 cases) . Four out of the 6 cryptococcosis patients had meningeal involvement . Systemic candidiasis (2 cases) and aspergillosis (1 case) were less common . Biotyping of yeasts isolated between September 1988 and February 1989 with the killer system revealed type 377 to be the most common among the C . albicans isolates . It represented 70% of all the yeasts isolated.

DICP, 1990 Dec, 24(12), 1175 - 6
Massive hepatic enlargement with fatty change associated with ketoconazole; Gradon JD et al.; Several forms of hepatic toxicity have been described with the antifungal agent ketoconazole . We report a case of massive liver enlargement with fatty infiltration presenting as gastric compression . This occurred in a young woman with AIDS taking ketoconazole as maintenance therapy for cryptococcal meningitis . This is the first reported case of ketoconazole causing fatty change in the liver.

Appl Environ Microbiol, 1990 Dec, 56(12), 3851 - 4
Microflora of partially processed lettuce; Magnuson JA et al.; Bacteria, yeasts, and molds isolated from partially processed iceberg lettuce were taxonomically classified . The majority of bacterial isolates were gram-negative rods . Pseudomonas, Erwinia, and Serratia species were commonly found . Yeasts most frequently isolated from lettuce included members of the genera Candida, Cryptococcus, Pichia, Torulaspora, and Trichosporon . Comparatively few molds were isolated; members of the genera Rhizopus, Cladosporium, Phoma, Aspergillus, and Penicillium were identified.

Ir Med J, 1990 Dec, 83(4), 157 - 8
Cryptococcal meningitis occurring in HIV infected individuals; Horgan M et al.; Three cases of cryptococcal meningitis in patients with HIV infection are described . A high index of suspicion is required for diagnosis . India ink preparation and culture of the CSF for cryptococcus is mandatory in HIV seropositive patients irrespective of the CSF white cell count and biochemistry.

Can J Microbiol, 1990 Dec, 36(12), 856 - 8
Utilization by yeasts of D-glucarate, galactarate, and L-tartarate is uncommon and occurs in strains of Cryptococcus and Trichosporon; Schneider H et al.; In 38 yeast genera tested, utilization of D-glucarate was uncommon, occurring with only 10 strains out of 373 . The ability was prominent among Cryptococcus strains, with 8 out of 8 tested being positive, including the pathogen Cryptococcus neoformans . The ability was present also in Trichosporon where 2 out of the 4 strains tested were positive . There was a correlation between ability to utilize D-glucarate, galactarate, L-tartarate, and D-glucuronate . Use of L-ascorbate occurred in more genera than use of D-glucarate, but all strains that grew on D-glucarate grew on L-ascorbate . The utilization of certain hydroxylated carboxylates by strains, mainly found in two genera, is of interest in identifying the catabolic pathways involved, in taxonomic studies, and in developing rapid methods of yeast identification.

Kekkaku, 1990 Dec, 65(12), 867 - 71
{Tuberculosis sequelae: secondary fungal infections}; Iwata H et al.; The antibody activities against Aspergillus fumigatus, Cryptococcus neoformans and Coccidioides immmitis by complement fixation (CF) were examined for active and cured pulmonary tuberculosis in 1985, and against Aspergillus fumigatus and Candida albicans by indirect hemagglutination (IHA) and counterimmunoelectrophoresis (CIE) in 1986 . The antibody activity against Aspergillus by CF was positive in 8.6% of the sera and negative against Cryptococcus, and Coccidioides . The IHA results were positive in 2.9% against Aspergillus and in 44.9% against Candida . The CIE results were positive in 19.5% against Aspergillus and in 16.3% against Candida . Based on chest X-ray films, the development of pulmonary candidiasis was non-specific but that of pulmonary aspergilloma in tuberculous cavities was specific . Before aspergillomas were formed, the tuberculous cavities had become thin-walled . Then the cavities increased or decreased in size . It is postulated that the cavity has tension when check-valved by mycetome in the drainage bronchus, and becomes smaller or distinct when ventilated inadequately . In cases cavities do not change in size due to intracavitary proliferation of Aspergillus, the wall of cavity is rough, prominent, or opaque.

Mycopathologia, 1990 Nov, 112(2), 113 - 8
A toxic substance produced by Nocardia otitidiscaviarum isolated from cutaneous nocardiosis; Mikami Y et al.; During our studies on toxic substances from clinically isolated Nocarida, a new isolate identified as Nocardia otitidiscaviarum from cutaneous nocardiosis was found to produce a toxic substance called HS-6 that had strong in vitro as well as in vivo toxicity . The mouse intraperitoneal LD50 value was 1.25 mg/kg and the ED50 value for L1210 cultured cells was 0.3 ng/ml . The structure of HS-6 was determined and found to belong to the 16-membered macrocyclic group with a molecular formula of C43H68O12 . HS-6 also showed activity against pathogenic fungi such as Cryptococcus neoformans.

Ann Cardiol Angeiol (Paris), 1990 Nov, 39(9), 519 - 25
{Cardiac involvement in carriers of the human immunodeficiency virus . Report of 38 cases}; Blanc P et al.; The anatomopathological study of the heart, carried out during the autopsy of a series of 38 subjects seropositive for the human immunodeficiency virus, has enabled the observation of histological lesions in 23 cases (60%) . The heart affection is more often asymptomatic since it has been clinically suspected in only four cases . A myocarditis is present in 42 p . cent of the cases, and lesions specific to a pathogenic agent are visible in half of the myocarditis cases . These pathogenic agents are: toxoplasma (2 cases), cryptococcus (2 cases), candida (1 case), aspergillus (1 case) and cytomegalovirus (1 case) . Lymphocytic myocarditis, with no isolated aetiological agent, and without viral inclusion, has been observed in 9 cases . The histological affection of the pericardium is observed in 4 cases and that of the endocardium in 3 cases . The lesions are not specific . The cardiotropism of the HIV is suspected, but not established . It could explain the frequency of lymphocytic myocarditis and dilated cardiomyopathies observed in HIV positive patients . The frequency of heart localizations in HIV positive subjects, even strictly asymptomatic as observed in this study, leads us to advise a systematic specialized cardiac examination.

Nihon Kyobu Shikkan Gakkai Zasshi, 1990 Nov, 28(11), 1436 - 41
{Step section preparation of transbronchial lung biopsy material in diffuse lung disease}; Nagata N et al.; We retrospectively prepared step sections of the transbronchial lung biopsy (TBLB) materials which revealed nondiagnostic findings in their original sections in patients with diffuse lung disease, and evaluated the significance of the examination of step sections in the diagnosis of diffuse lung disease . Of 131 cases with nondiagnostic TBLB findings, the preparation of step sections resulted in specific findings in 6 cases (malignancy 3 cases, tuberculosis 1 case, cryptococcosis 1 case and viral infection 1 case), and histopathological changes consistent with the clinical diagnosis in 25 cases . The step section preparation was especially useful for the detection of epithelioid granuloma and tumor tissue in patients with sarcoidosis and carcinoma, respectively, while its contribution to the diagnosis of collagen-vascular disease, hypersensitivity pneumonitis, atypical pneumonia and pneumoconiosis was relatively small . The step section preparation was also useful for the detection of bronchiolitis obliterans . In addition, step sections uncovered clinically unnoticed infection (purulent exudate in the alveolar space) in 6 cases, 3 of whom actually developed pneumonia thereafter . Thus, the preparation of step sections was considered to be useful clinically in 37 cases (28.2%) . The preparation of step sections is recommended before a further diagnostic procedure is chosen, when TBLB performed in patients with diffuse lung disease reveals nondiagnostic findings.

Clin Neuropathol, 1990 Nov-Dec, 9(6), 284 - 9
Neoplastic angioendotheliomatosis (NAE) of the CNS in a patient with AIDS subacute encephalitis, diffuse leukoencephalopathy and meningo-cerebral cryptococcosis; Dozic S et al.; A 12-year-old, hemophilic boy died with acquired immune deficiency syndrome (AIDS) after a clinical course characterized by progressive psycho-organic syndrome and opportunistic infections . Postmortem neuropathological examination revealed a cerebral form of neoplastic angioendotheliomatosis (NAE), leukoencephalopathy, giant cell encephalitis and meningo-cerebral cryptococcosis . The most unusual finding was the presence of proliferated neoplastic cells within lumina of some blood vessels throughout the central nervous system (CNS) . These cells displayed cytologic features of malignancy and stained positively for common leukocyte antigen . Coronal sections showed diffuse cerebral and cerebellar leukoencephalopathy with most pronounced loss of myelin and axons in deep white matter, while the subcortical arcuate fibers and the corpus callosum were partially spared . In these areas numerous small foci of severe myelin loss were present . Microglial nodules and distinctive multinucleated giant cells (MGC) were numerous . Intracytoplasmic and intranuclear acidophilic inclusions were found in a few multinuclear and mononuclear cells . Close contact between mononuclear and multinuclear cells suggesting their fusion was also observed . As far as we know this is the first case of NAE encountered in AIDS, one of the rare primary cerebral forms and the youngest reported case of NAE up to now . This case could be considered as one proof more that NAE is a special form of malignant lymphoma.

J Clin Microbiol, 1990 Nov, 28(11), 2565 - 7
Comparison of Guizotia abyssinica seed extract (birdseed) agar with conventional media for selective identification of Cryptococcus neoformans in patients with acquired immunodeficiency syndrome; Denning DW et al.; Growth of Cryptococcus neoformans from the sputum of patients with acquired immunodeficiency syndrome may be obscured by oral contamination with Candida albicans on conventional media . We prospectively compared direct plating of sputum and urine onto birdseed agar and compared birdseed agar plating with plating onto Mycosel and Sabouraud dextrose agar cultures . Thirty-two sputum and three urine specimens were compared . C . neoformans was isolated from five specimens . In two specimens, one of sputum and one of urine, C . neoformans was detected only on the birdseed agar plate because of overgrowth on the conventional media by C . albicans . C . neoformans produced dark colonies on birdseed agar, unlike C . albicans, which produces white colonies . The use of birdseed agar as the primary culture medium for sputum and urine specimens from patients with acquired immunodeficiency syndrome increases sensitivity for C . neoformans.

Vet Clin North Am Small Anim Pract, 1990 Nov, 20(6), 1615 - 32
Recently described feline dermatoses; Medleau L; This article discusses the etiology, clinical signs, diagnosis, and treatment of several diseases . Feline immunodeficiency, virus infection, cryptococcosis, dermatophyte pseudomycetomas, demodicosis, Sezary-like syndrome, and discoid lupus erythematosus in cats are reviewed.

Infect Immun, 1990 Nov, 58(11), 3508 - 15
Aspergillus fumigatus complement inhibitor: production, characterization, and purification by hydrophobic interaction and thin-layer chromatography; Washburn RG et al.; Aspergillus fumigatus has previously been shown to produce a soluble extracellular inhibitor of the alternative complement pathway, called Aspergillus complement inhibitor, or CI . We now report an efficient method for production of CI which relies on the fact that poorly conidiating cultures yielded CI activity with approximately sevenfold-higher potency than CI produced by conidiating cultures . CI from poorly conidiating cultures provided 50% inhibition of alternative pathway-mediated binding of 125I-labeled complement component C3 to cryptococcal blastoconidia at a mean concentration of 60 micrograms/ml . The ability of crude CI to inhibit the alternative complement pathway seemed to be independent of intact protein or polysaccharide structure, as evidenced by resistance of inhibitory activity to digestion by proteases, including subtilisin, alpha-chymotrypsin, papain, and pepsin as well as endoglycosidases F and H . Separation of the active inhibitory component of CI from contaminating materials contained in crude CI preparations was achieved by using Phenylsuperose hydrophobic interaction chromatography in a fast protein liquid chromatography system . The active material proved to be extremely hydrophobic, desorbing from the column only during elution with ethanol; it contained only 15% protein and 5% polysaccharide . Furthermore, results from preparative thin-layer chromatography indicated that lipids which comigrated with phosphatidylserine/phosphatidylinositol and phosphatidylethanolamine possessed significant complement-inhibitory activity . Taken together, these data suggested that phospholipids from A . fumigatus contributed to the functional activity of CI.

Chest, 1990 Nov, 98(5), 1060 - 6
Pulmonary manifestations of disseminated cryptococcosis in patients with AIDS; Chechani V et al.; Forty-eight patients with disseminated cryptococcosis and AIDS were retrospectively studied to define the pulmonary manifestations . Cryptococcus neoformans (CN) was first isolated from a pulmonary site in 12 patients . Disseminated disease was subsequently documented in all these patients . Symptoms and roentgenographic manifestations (normal, nodular/circumscribed infiltrates, pleural effusions, lobar consolidation) were diverse . Interstitial infiltrates predicted the presence of another opportunistic lung infection besides cryptococcosis in five patients (three untreated and two treated patients) . Infectious causes other than cryptococcosis were established by culture and clinical course in five of the ten patients who developed chest roentgenographic abnormalities during amphotericin B therapy . Endobronchial abnormalities were identified in four patients at bronchoscopy . Bronchoalveolar lavage (9/9) and pleural fluid (3/3) cultures were sensitive tests for detection of pulmonary involvement with CN.

Cesk Epidemiol Mikrobiol Imunol, 1990 Nov, 39(6), 335 - 46
{Urban cycles of zoonotic mycoses}; Ditrich O et al.; Based on their own results assembled during mycological examinations of 9958 subjects, 5496 animals and 648 specimens of non-animal substrates, and using data from the literature, the authors tried to formulate general laws concerning the prevalence of causal agents of mycoses with a zoonotic character which circulate steadily in urban areas: Microsporum canis, M . persicolor, Trichophyton mentagrophytes, M . equinum and T . equinum, T . verrucosum, some geophilic dermatophytes, Cryptococcus neoformans and Emmonsia crescens . In the characteristics of different urban cycles they used as a basis the evaluation of the prevalence of reservoir animals and reservoir substrates on the territory of towns and the evaluation of the most frequent routes of transmission of the agents from extrahuman sources to man . Preventive provisions leading to a reduction of the risk of the disease in humans must be specific with regard to different urban cycles.

Rev Inst Med Trop Sao Paulo, 1990 Nov-Dec, 32(6), 456 - 60
Coagglutination test (COA) for Cryptococcus neoformans circulating antigen detection in cerebral spinal fluid (CSF); Cano MI et al.; We tested 82 CSF of 24 renal transplanted patients (RT) with cerebral cryptococcosis, 8 CSF of asymptomatic RT patients, 43 CSF of proven cryptococcosis cases (positive control) and 35 CSF of patients with other diseases (histoplasmosis, paracoccidioidomycosis and bacterial infections) as negative control . The RT CSF were cultured in Sabouraud agar slant added with sunflower seeds and both control and RT CSF were qualitatively examined by cryptococcosis latex test (Crypto-LA test) . The COA test was developed both qualitatively and quantitatively . The highest titre encountered was 1:2048 . No false reactions appeared among the controls . The diagnostic value demonstrated by Galen and Gambino's method was: sensitivity--92.1%; specificity--92.6% and efficiency--92.3% . Besides that, the COA proved to be quick, exact and cheap, but it depends on CSF and sera pre-treatment, in order to avoid autoagglutination and increase its sensibility.

AJNR Am J Neuroradiol, 1990 Nov-Dec, 11(6), 1235 - 45
Encephalopathy in AIDS patients: evaluation with MR imaging; Flowers CH et al.; The presence and extent of encephalopathy were evaluated in 47 patients with AIDS or AIDS-related complex (ARC) by the use of MR imaging . Twenty-nine (62%) of the patients showed some form of white matter disease, exhibited as high signal intensity on T2-weighted images . Focal white matter lesions were seen in 23 (49%) of the patients, while a diffuse white matter process was observed in six patients (13%) . Of the 29 patients who had white matter disease on MR scans, 17 (36%) had a suggestion of white matter involvement on an initial CT study . Meanwhile, 12 (26%) of the patients had a normal CT scan on the initial examination . MR findings showed predominant disease in the subinsular and peritrigonal white matter areas . Marked cerebral atrophy was observed in 17 (36%) of 47 patients, cerebellar atrophy in 18 (38%), and brainstem atrophy in seven patients (15%) . Pathologic findings showed that toxoplasmosis was present in eight patients (17%), and primary CNS lymphoma was present in three patients (6%) . Cryptococcal meningitis was noted in two (4%) of the patients at autopsy, and Mycobacterium tuberculosis was seen in one (2%) of the patients at autopsy . MR imaging has been shown to be a valuable technique for the detection of encephalopathy in AIDS patients.

Enferm Infecc Microbiol Clin, 1990 Nov, 8(9), 548 - 52
{Bacteremia and fungemia in patients with AIDS . Study of 56 episodes}; Ruiz I et al.; We report 56 episodes of bacteremia and fungemia in 45 patients (23%) out of overall 193 cases of AIDS . 41% of the isolates were gram-negative bacilli, with a predominance of Salmonella enteritidis (30%), most of them community-acquired . Gram-positive cocci (18 episodes) were hospital-acquired in 61%, with a predominance of Staphylococcus sp (10 cases) . Mycobacteria and Cryptococcus neoformans were isolated in 8 patients . 88.8% of our patients with cryptococcosis (8/9) had positive blood cultures . 76% of the episodes (43/56) were community-acquired, with a high incidence of primary bacteremias (59%) . 48% of the patients were cured, whereas 27% died from causes related with the bacteremia.

Trans R Soc Trop Med Hyg, 1990 Nov-Dec, 84(6), 800 - 2
Infection with Pneumocystis carinii is prevalent in healthy Gambian children; Wakefield AE et al.; Pneumocystis pneumonia is rarely identified in the many immunosuppressed individuals with acquired immune deficiency syndrome (AIDS) and malnutrition in Africa . To test whether infection with Pneumocystis carinii occurs in the continent we conducted a comparative serological study, measuring by enzyme-linked immunosorbent assay antibodies to the parasite in 150 healthy young individuals from both Britain and the Gambian savanna . The prevalence of significant titres of antibody to P . carinii steadily increased with age and included more than 70% of both populations by 8 years of age . Infection with P . carinii is, therefore, common in the Gambia . Thus opportunistic pneumocystis pneumonia may be an important but largely unrecognized disease in the continent, though its impact is probably diminished by the prevalence of fatal tuberculous infection, particularly in the AIDS populationPIP: The prevalence of sero-positivity toward Pneumocystis carinii parasite antigens was determined in 150 British subjects aged 3 months-40years, and in 150 Gambians of the same age age range . The Gambians were from Katabas villages north of the Gambian river . The sera were tested with an ELISA assay developed from parasites and cysts isolated from rats, which were previously shown to share many antigens with organisms from humans . IgG titers reactive with P . carinii increased with age in the British and Gambian subjects, with essentially no positives at ages 3-6 months, to a peak of 70% positive in both groups by age 8 years . British children and parents were questioned about history of pneumonia illness, with negative findings . There are very few reports of P . carinii infections, judging from sputum and bronchoscopic lavage, in African AIDS patients . 2 cases of Cryptococcus have been reported, but tuberculosis is a common and rapidly lethal infection in African AIDS patients .

Pathologica, 1990 Nov-Dec, 82(1082), 663 - 77
{AIDS pathology: various critical considerations (especially regarding the brain, the heart, the lungs, the hypophysis and the adrenal glands}; Giampalmo A et al.; Our studies on pathology of AIDS point to four major conclusions . 1) The brain is often directly affected by the HIV infection (with the characteristics of subacute microglial encephalitis with pathognomonic multinucleated giant cells) and then by opportunistic infections such as Cytomegalovirus, Herpes-virus, Papova-virus JC (with progressive multifocal leucoencephalopathy), Mycobacterium tuberculosis, Toxoplasma gondii, Cryptococcus neoformans, Candida albicans and Aspergillus fumigatus; opportunistic neoplasms (i.e . B cell lymphoma mostly pluricentric) could also developed . 2) The heart is frequently involved as well; perivascular sclerosis and myocytolysis are the hallmarks of a peculiar cardiomyopathy . 3) In the lung viral, bacterial, fungal an protozoan severe infections are frequently present: common are those caused by Cytomegalovirus and Pneumocystis carinii . Frequently thin fibrotic interalveolar septa are observed (with consequent alteration of hematosis) . 4) Adrenal (most frequently) and pituitary may display necrotic-hemorragic areas (in adrenals chiefly due to Cytomegalovirus) . These may be extensive enough to explain the occurrence of clinical syndromes of endocrine insufficiency.

Antimicrob Agents Chemother, 1990 Nov, 34(11), 2055 - 60
Improvement of amphotericin B activity during experimental cryptococcosis by incorporation into specific immunoliposomes; Dromer F et al.; Cryptococcosis is an opportunistic infection that is responsible for increased morbidity and mortality in patients with the acquired immunodeficiency syndrome . The high toxicity of the antifungal agent that is mainly used against cryptococcosis, amphotericin B (AMB), accounts for the need for new treatments, especially in patients with the acquired immunodeficiency syndrome because of the high relapse rate of cryptococcosis . Drug targeting may be one of these alternate treatments . Since we have demonstrated that an immunoglobulin G1 (IgG1) anti-Cryptococcus neoformans serotype A monoclonal antibody (E1) was protective during experimental cryptococcosis in mice, we investigated whether specific targeting of AMB with liposomes that bear E1 would improve the therapeutic index of the drug . For that purpose, in vitro and in vivo experiments were designed to compare the specificities and activities of these liposomes with those of control immunoliposomes bearing a nonrelated IgG1 monoclonal antibody (CY34) . The immunoliposomes were prepared by covalently linking E1 or CY34 and small unilamellar vesicles . When immunoliposomes were incubated with yeast cells, only E1-bearing liposomes recognized C . neoformans . In vivo, mice that were treated 24 h after infection with one injection of AMB (0.12 mg/kg of body weight) intercalated into E1-bearing liposomes survived significantly longer than did those given the same dose of AMB alone or AMB intercalated into nontargeted liposomes or control immunoliposomes . None of the mice that were given control treatments did statistically better than those that were given AMB . Keeping in mind that this kind of therapy requires knowledge of the antigenic type of the infecting organism, the results suggest that specific targeting of small doses of AMB improve the efficacy of AMB and might be an alternative to the use of larger doses of AMB.

Lancet, 1990 Oct 13, 336(8720), 923 - 5
Ecology, life cycle, and infectious propagule of Cryptococcus neoformans; Ellis DH et al.; Cryptococcus neoformans is a biotrophic smut-like fungus, and the epidemiology of cryptococcosis can mainly be explained by exposure to an infective aerosolised inoculum . For C neoformans var gattii it is postulated that the principal infectious propagule is the basidiospore and that exposure to Eucalyptus camaldulensis, the host tree, is required to initiate infection in man and animals . C neoformans var gattii may have been exported from Australia by infected seeds of E camaldulensis containing dormant dikaryotic mycelium of the fungus . For C neoformans var neoformans both the basidiospore and desiccated encapsulated yeast cells are postulated to act as infectious propagules, the basidiospores showing a seasonal distribution in association with an as yet unidentified host plant, and the encapsulated yeast cells dispersed from accumulations of dried bird (mainly pigeon) droppings which act as a year-round vector.

Rev Prat, 1990 Oct 11, 40(23), 2136 - 40
{Clinical aspects of AIDS in Africa}; Itoua-Ngaporo A; The clinical manifestations of HIV infection in Africa are similar to those observed in Europe and North America . However, some features related to ecological and diagnostic factors give the disease a certain African peculiarity . In more than 80 p . 100 of the cases AIDS is characterized by deep alteration of the subject's general condition, with chronic diarrhoea, severe asthenia, prolonged fever and massive loss of weight . This "slim disease" is only found at the terminal stage of AIDS in North America . Opportunistic infections are multiple, often associated, and their frequency differs from that found in Europe and the USA . Thus, pulmonary pneumocystosis is rare (12.5 to 21 p . 100 of the cases, as against 50 to 80 p . 100 in Europe) . Isosporosis is frequent (4 to 48 p . 100 of the cases instead of 0.2 p . 100 in the USA), and this also applies to cryptosporidiosis (7 to 21 p . 100 of the cases, compared with 3.3 p . 100 in the USA) . Gastrointestinal candidiasis occurs in 21 to 49 p . 100 and cryptococcosis in 10 to 30 p . 100 of the patients . Material problems make it impossible to evaluate the prevalence of certain infections, notably toxoplasma and CMV infections . The prevalence of Kaposi's sarcoma is low (15 to 20 p . 100) . Dermatological manifestations occur at an early stage and are both common and varied (papular eruption, prurigo, herpes zoster, changes in the hair and skin appearance); they characterize the "African aspect" of AIDS . Tuberculosis is particularly frequent: in Africa, 30 to 40 p . 100 of tuberculous patients are HIV seropositive, as opposed to 10-25 p . 10 in Western countries.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbohydr Res, 1990 Oct 10, 206(2), 251 - 6
Hydrolysis of (1----3)- and (1----2)-beta-D-xylosidic linkages by an endo-(1----4)-beta-D-xylanase of Cryptococcus albidus; Vrsanska M et al.; The substrate specificity of an endo-(1----4)-beta-D-xylanase of the yeast Cryptococcus albidus was investigated using a series of methyl beta-D-xylotriosides . In addition to (1----4) linkages, the enzyme could cleave (1----3) and (1----2) linkages adjacent to a (1----4) linkage and further from the non-reducing end of the substrate . The enzyme could hydrolyse a (1----3) linkage that attached a terminal xylopyranosyl group to a (1----4)-linked xylobiosyl moiety . The enzyme did not attack alpha-D-xylosidic linkages . The rate of cleavage of (1----4) linkages was much higher than those of other linkages at 0.5mM substrate, but the rates were comparable at 20mM substrate when transglycosylation reactions also occurred that facilitated degradation of the substrates.

Infect Immun, 1990 Oct, 58(10), 3300 - 6
Pathogenesis of Cryptococcus neoformans in congenitally immunodeficient beige athymic mice; Salkowski CA et al.; Mortality after intravenous challenge with 10(4) Cryptococcus neoformans demonstrated that doubly immunodeficient beige athymic (bg/bg nu/nu) mice were more susceptible to systemic cryptococcosis than either bg/bg or nu/nu mice . Infected bg/bg nu/nu mice also had a shortened lifespan compared with their bg/bg nu/+ littermates . Beige athymic (bg/bg nu/nu) but not bg/bg nu/+mice developed cryptococcal lesions in the skin, demonstrating that C . neoformans is dermatotropic in a T-cell-deficient host . Higher numbers of C . neoformans were isolated from the lungs and spleen of infected bg/bg nu/nu than bg/bg nu/+ mice as early as day 3 after challenge, indicating that in lymphoid-rich organs, T cells can alter the course of systemic cryptococcosis early in the infection . Despite extensive abscess formation in the brains of bg/bg nu/+ mice, dissemination and growth rate of C . neoformans in the brain was similar in both genotypes . The primary histopathological feature in tissues from bg/bg nu/nu mice infected with C . neoformans consisted of foci of encapsulated yeast cells with minimal to no inflammatory response . In contrast to bg/bg nu/nu mice, bg/bg nu/+ mice mounted a vigorous inflammatory response to C . neoformans that progressed from acute to chronic inflammation . Beige athymic mice are a new animal model that will be useful in clarifying the innate and acquired immune factors important in resistance to cryptococcosis.

Br J Ophthalmol, 1990 Oct, 74(10), 610 - 4
Choroidal lesions in patients with AIDS; Rosenblatt MA et al.; Seven cases of bilateral, scattered, yellow-white choroidal lesions have been seen in AIDS patients since January 1988 . One resulted from presumed extension of cryptococcal meningitis into the optic nerve and choroid . All the remaining six patients had pneumocystis pneumonia at some time during the course of the disease and were receiving aerosolised pentamidine therapy . None died quickly of disseminated Pneumocystis carinii infection, unlike previously reported patients . Mycobacterial infection was also present in five of these six patients . The differential diagnosis of this entity in AIDS patients is discussed.

Aust N Z J Med, 1990 Oct, 20(5), 645 - 9
Cryptococcosis in a renal unit; Kong NC et al.; Cryptococcosis is a known opportunistic infection in immunosuppressed hosts . We report our experience of all cases presenting to our Department between December 1975 and September 1988 . Eight post-renal transplant patients and three systemic lupus erythematosus (SLE) patients were affected . All were receiving treatment with steroids, in association with either azathioprine or cyclosporin . The diagnosis of cryptococcal meningitis was initially based on a positive cerebrospinal fluid (CSF) cryptococcal antigen, by latex agglutination test, and subsequently confirmed by cultures . Common clinical presentations, in descending order of frequency, included headaches, fever, mental confusion, epilepsy and papilloedema . Meningism was not a prominent feature . CT brain scans were obtained in eight patients and one showed a focal lesion and one showed cerebral atrophy . Four patients also had an abnormal chest X-ray (CXR) and one had disseminated cryptococcosis . Amphotericin and 5-fluorocytosine were the mainstay of therapy, although ketoconazole alone was subsequently used in three selected patients with cure . Four early deaths occurred in patients with delayed diagnosis and treatment, usually in association with other severe concurrent infections . We conclude that awareness of cryptococcosis is essential in immunocompromised hosts presenting with headache with, or without, mental confusion or fever.

Mycopathologia, 1990 Oct, 112(1), 27 - 32
Polyamine depletion and growth inhibition of Cryptococcus neoformans by alpha-difluoromethylornithine and cyclohexylamine; Pfaller MA et al.; The ability of two known inhibitors of polyamine synthesis alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase (ODC), and cyclohexylamine, an inhibitor of spermidine synthase, to inhibit the in vitro growth and polyamine synthesis of clinical isolates of Cryptococcus neoformans was examined . Treatment of C . neoformans with either DFMO or cyclohexylamine resulted in depletion of cellular polyamines and inhibition of growth . Cryptococcus neoformans was shown to lack detectable spermine and to require high concentrations of spermidine, but not putrescine, for growth . The growth inhibition by DFMO and cyclohexylamine was reversed by exogenous polyamines . These findings document the ability of cyclohexylamine and DFMO to inhibit polyamine synthesis and growth in clinically important isolates of C . neoformans.

Am J Gastroenterol, 1990 Oct, 85(10), 1421 - 4
Disseminated, nonmeningeal gastrointestinal cryptococcal infection in an HIV-negative patient; Daly JS et al.; Gastrointestinal cryptococcosis is extremely rare, especially in patients with no involvement of the central nervous system . We describe a 63-yr-old man undergoing prednisone therapy for chronic hepatitis and cirrhosis who presented with peritonitis, colitis, and skin lesions . Pathological studies revealed necrosis and numerous cryptococcal organisms in the colon, omentum, and skin, and cultures yielded Cryptococcus neoformans . The patient died of multisystem organ failure following emergency exploratory surgery performed when he had onset of symptoms of a bowel perforation after an endoscopic biopsy . Clinicians should be aware that gastrointestinal cryptococcosis can occur in the absence of infection of the central nervous system or lungs, and that it may affect relatively healthy patients who are immunocompromised because of splenectomy, chronic liver disease, or steroid therapy.

Ann Intern Med, 1990 Oct 1, 113(7), 520 - 4
Chemotherapy for advanced thymoma . Preliminary results of an intergroup study; Loehrer PJ Sr et al.; OBJECTIVE: To determine the efficacy of combination therapy with cisplatin, doxorubicin, and cyclophosphamide alone or with radiotherapy for patients with extensive and those with limited unresectable thymoma . DESIGN: Nonrandomized, prospective phase I-II trial . SETTING: A Cooperative Oncology Group trial involving tertiary medical centers . PATIENTS: Twenty of twenty-two patients with measurable, extensive or limited, unresectable thymoma were evaluable for response . INTERVENTION: Patients were given cisplatin, 50 mg/m2 body surface area, doxorubicin, 50 mg/m2, and cyclophosphamide, 500 mg/m2, on day 1, with cycles repeated every 21 days until progression or until the maximally tolerated total doxorubicin dosage (for example, 450 mg/m2) was reached . Intravenous hydration with normal saline was administered during treatment courses . For responding patients with limited disease, 4500 cGy was administered to primary tumors after the second cycle of chemotherapy and before the initiation of the third cycle . MEASUREMENTS AND MAIN RESULTS: Three complete and eleven partial remissions were seen in 20 evaluable patients, for a total response rate of 70% (95% CI, 46% to 88%) . The median duration of remission was 13 months with three patients remaining continuously disease free for over 2 years . The median survival time of all eligible patients was 59 months (CI, 22 months to infinity) . Four patients developed infections, including listerial and aseptic meningitides, mucocutaneous candidiasis, and cryptococcal pneumonia, that were indicative of a defect in cell-mediated immunity . CONCLUSIONS: Combination therapy with cisplatin, doxorubicin, and cyclophosphamide frequently produces objective remissions in patients with advanced thymoma . Further experience with this treatment regimen is warranted to clarify potential prognostic factors in patients with unresectable thymoma.

Doc Ophthalmol, 1990 Oct, 75(3-4), 315 - 20
Periorbital necrotising fasciitis due to Cryptococcus neoformans in a healthy young man; Doorenbos-Bot AC et al.; A case report is presented of a healthy 25-year-old man who developed a periorbital necrotising fasciitis after a trivial trauma with a wooden splinter . Necrotising fasciitis of the eyelids occurs rarely . Cryptococcus neoformans is not described as a causative factor of necrotizing fasciitis . Cryptococcus neoformans usually infects patients with immunodeficiencies, diabetes mellitus or steroid therapy . This patient was healthy and developed a periorbital necrotising fasciitis due to Cryptococcus neoformans.

Lancet, 1990 Sep 29, 336(8718), 763 - 5
Antimicrobial actions of calcium binding leucocyte L1 protein, calprotectin; Steinbakk M et al.; The calcium binding L1 protein was found to inhibit growth of blood culture isolates of Candida spp and cerebrospinal fluid isolates of Cryptococcus neoformans . Minimum inhibitory concentrations (MIC) were 4-128 mg/l, and concentrations 2-4 times the MIC were fungicidal . Blood culture isolates of Escherichia coli, Klebsiella spp, Staphylococcus aureus, and Staphylococcus epidermidis had MIC values of 64-256 mg/l . Antibacterial activity was strongly influenced by the nature of the culture medium . In view of the biological activity of L1, the name calprotectin is proposed to describe this antimicrobial protein with calcium binding properties.

Pneumonol Pol, 1990 Sep-Oct, 58(9-10), 544 - 8
{A case of skin cryptococcosis in systemic lupus erythematosus}; Halweg H et al.; Here is presented a case of woman treated by immunosuppressive preparations because of systemic lupus erythematosus with ski manifestations as tubercles and ulcerations on skin of trunk and extremities . On the basis of histological examination of tubercle skin specimens and mycological examinations of material obtained from skin ulcerations cryptococcosis was diagnosed . Disease was limited to skin that was an entry of infection . Patient was treated by Amphotericin B administered intravenously and Flucitosine per os . Amphotericin B was also applied topically . The results of cultures became gradually negative, up to total disappearance of fungus cells in direct specimens, prepared from examined material . After treatment continuing for 5 months only discoloured scars were observed on sick skin.

Antimicrob Agents Chemother, 1990 Sep, 34(9), 1648 - 54
Collaborative investigation of variables in susceptibility testing of yeasts; Pfaller MA et al.; A multicenter study was performed to evaluate the effect of medium, incubation time (24 and 48 h), and temperature (30 and 35 degrees C) on intra- and interlaboratory variations in MICs of flucytosine, amphotericin B, and ketoconazole for yeasts . Testing was performed on coded isolates of Candida species (11 strains) and Cryptococcus neoformans (2 strains) by using a standard macrodilution protocol 11 laboratories . Four chemically defined media buffered to pH 7.0 with morpholinepropanesulfonic acid were evaluated, including buffered yeast nitrogen base, synthetic amino acid medium-fungal, RPMI 1640 medium, and high-resolution antifungal assay medium . Intralaboratory variability was less than or equal to fourfold for 97% of the replicate sets of data . The highest level of interlaboratory agreement, irrespective of antifungal agent or incubation conditions, was observed with RPMI 1640 medium . Intralaboratory variability was less than or equal to fourfold for 93% of the determinations with ketoconazole and 100% with flucytosine tested in RPMI 1640 medium at 35 degrees C for 24 h . Variability in amphotericin B results was less than or equal to fourfold for 81% of the determinations in RPMI 1640 medium at 35 degrees C for 48 h . The rank order of MICs within each antifungal test group was similar among the various laboratories and was generally in agreement with the reference rank order regardless of the test medium that we used.

Indian J Med Res, 1990 Sep, 91, 382 - 5
Reactivity of Cryptococcus neoformans & Candida species with concanavalin A & blood grouping sera; Mishra SK et al.; Forty strains of Cryptococcus neoformans, 30 of Candida albicans, 24 of C . parapsilosis and 10 strains each of C . tropicalis and C . (Torulopsis) glabrata were examined . A 0.2 per cent solution of concanavalin A (Con A) in phosphate buffered saline and commercial anti-A and anti-B blood grouping sera were used in the whole cell slide agglutination test . All the isolates of Candida species strongly reacted with Con A and over 90 per cent were agglutinated by anti-A and -B blood grouping sera . In contrast, except for one strain, Cryptococcus neoformans did not agglutinate with Con A or blood grouping sera . These findings suggest, on one hand, a fundamental difference in the sugar mosaic of the cell surface components of Cryptococcus neoformans and Candida species, and on the other, presence of similar antigenic determinant(s)/receptors on the cell surface of Candida species and human erythrocytes.

DICP, 1990 Sep, 24(9), 860 - 7
Fluconazole: a new triazole antifungal agent; Pasko MT et al.; Fluconazole is a fluorine-substituted, bis-triazole antifungal agent . Its mechanism of action, like that of other azoles, involves interruption of the conversion of lanosterol to ergosterol via binding to fungal cytochrome P-450 and subsequent disruption of fungal membranes . Activity against Aspergillus spp., Blastomyces dermatitidis, Candida spp., Coccidioides immitis, Cryptococcus neoformans, Histoplasma capsulatum, and Paracoccidioides brasiliensis has been demonstrated in several animal models . Fluconazole can be administered both orally and intravenously . Mean peak serum concentrations achieved in human volunteers after 50 and 100 mg (oral) are 3.1 and 7.0 mumols/L respectively . Protein binding is low (11 percent) and cerebrospinal fluid to serum ratio is 0.58 to 0.89 . Serum half-life is long (22-32 hours) and elimination is via renal clearance of unchanged drug . Clinical trials and reports support the use of fluconazole in treatment of candidiasis, particularly oropharyngeal and esophageal infections in immunocompromised hosts . Fluconazole is also approved for initial and suppressive therapy of cryptococcal meningitis . Its role in management of systemic fungal infections will be further defined once results of other comparative trials become available . Fluconazole is well tolerated and its effects on steroidogenesis are markedly less than those of ketoconazole . Antipyrine clearance is not altered at low doses (50 mg) of fluconazole; however, drug interactions with the use of larger doses can be anticipated with agents such as cyclosporin, phenytoin, oral hypoglycemics, and warfarin . Rifampin appears to decrease metabolic clearance of fluconazole . Fluconazole is available as oral and parenteral formulations . Once-daily doses of 100-400 mg are recommended . Dosage reduction is advised for patients with impaired renal function.

No To Shinkei, 1990 Sep, 42(9), 863 - 6
{Successful treatment of Candida meningitis with miconazole}; Fukui S et al.; This paper presents a case of successful treatment of candida meningitis with miconazole . A 55-year-old woman was admitted due to high fever, vomiting and urinary incontinence on November 11, 1986 . Four months prior to this episode, she had been treated for a ruptured aneurysm with neck-clipping and V-P shunt for NPH . Candida albicans was cultured from her CSF . The shunt system was immediately removed and an Ommaya's reservoir was installed for external drainage and intrathecal administrations . Combination therapy (amphotericin B and flucytosine) was initiated . However, it was discontinued after ten days because of high fever and chills after intrathecal injection of amphotericin B . Treatment with miconazole intrathecally (10-90 mg/week, total 565 mg) and intravenously (200-1200 mg/day, total 70.4 g) was begun on November 23 . Clinical and CSF findings were improved soon . No side effect of miconazole was observed . After V-P shunt revision, she was discharged without neurological deficit on March 12, 1987 . Reports of mycosis in central nervous system are recently increasing, especially for candidosis . Cryptococcosis is noted frequently as an opportunistic infection of AIDS . The administration of amphotericin B and flucytosine has been the main therapy for mycotic meningitis . Unfortunately, however, Amphotericin B has many toxic effects, including renal dysfunction, and flucytosine can induce the emergent resistance . Miconazole has been used to successfully treat cryptococcosis, aspergillosis or coccidiosis, and was effective in our case of candida meningitis . Few side effects have been reported with its use . The intrathecal injection of miconazole is recommended for meningitis, because the drug is taken up minimally into CSF space after intravenous administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Rev Infect Dis, 1990 Sep-Oct, 12(5), 768 - 77
Spectrum of Cryptococcus neoformans infection in 68 patients infected with human immunodeficiency virus; Clark RA et al.; Sixty-eight patients infected with human immunodeficiency virus (HIV) and Cryptococcus neoformans who presented to three major medical centers in New Orleans, Louisiana, were studied retrospectively . In patients with meningitis the most common presenting symptoms were fever and headache . Those without central nervous system involvement generally had an isolated pulmonary infection due to C . neoformans and presented with cough and dyspnea . CSF parameters were abnormal in 41% of patients, and the India ink preparation was positive in 88% of patients with cultures of CSF positive for C . neoformans . The overall median survival time for the 47 patients who died was 5 months, with a range of 0-22 months . Of the 27 patients who received maintenance therapy with amphotericin B, two (7%) relapsed . The only factors found to be associated with a poor prognosis were abnormal computed tomography of the head and altered mental status on presentation . C . neoformans infections in HIV-infected patients remain difficult to treat and have a poor prognosis.

Mycopathologia, 1990 Sep, 111(3), 133 - 64
Review of animal mycoses in Australia; Connole MD; This review covers the available literature on the mycoses of animals in Australia since the last review published in 1967 . Of the cutaneous infections, dermatophytoses have been recorded in a wide range of animals: cattle, horses, goats, pigs, sheep, cats, dogs, mice, guinea-pigs, rabbits, a lion, kangaroos, a camel, koalas and wallabies . These infections were caused by several species and varieties of the genera, Microsporum and Trichophyton . Eight agents of ringworms have been recorded in the horse . Two subcutaneous mycoses, phaeohyphomycosis and sporotrichosis have been reported . Phaeohyphomycosis is becoming more common but sporotrichosis is rare having been recorded only once in a cat . The following systemic mycoses have been recorded: adiaspiromycosis, aspergillosis, candidiasis, cryptococcosis, dactylariosis, fusariomycosis, histoplasmosis, miscellaneous mycoses, mycotic abortion and related conditions, zygomycosis, pythiosis, protothecosis and green algal infections . Cryptococcosis has affected 11 different animal species . Mycotic abortion is a serious disease in Victoria . Pythiosis of horses has been extensively studied in northern Australia.

J Infect, 1990 Sep, 21(2), 175 - 81
The value of serum cryptococcal antigen in the diagnosis of cryptococcal infection in patients infected with the human immunodeficiency virus; Nelson MR et al.; Serum cryptococcal antigen titres were measured in 828 HIV-infected patients with pyrexia, 69 of whom had meningism . Serum cryptococcal antigen was positive in 17 patients of whom 16 had meningism with cryptococcus isolated from their CSF . The other patient had no meningism, had no evidence of cryptococcal infection on repeated CSF examination and remains well . A positive serum cryptococcal antigen test was therefore valuable in the diagnosis of cryptococcal meningitis, although in all 16 patients meningism was present and a diagnostic lumbar puncture was therefore carried out . In our experience routine screening for serum cryptococcal antigen did not predict patients who subsequently developed cryptococcal meningitis.

J Clin Microbiol, 1990 Sep, 28(9), 1938 - 41
Evaluation of the updated Vitek yeast identification data base; el-Zaatari M et al.; Using 398 isolates of yeasts and yeastlike fungi comprising 9 genera and 26 species, as well as the hyphomycete Geotrichum candidum and the achlorophyllous alga Prototheca wickerhamii, we compared the API 20C yeast identification system with the modified Vitek yeast identification system with an expanded data base . We found 11 discrepancies between the two systems: five (1.3%) of the isolates (Blastoschizomyces capitatus, 1; Candida albicans, 1; Hansenula anomala, 1; Rhodotorula minuta, 2) had biocodes not included in the expanded Vitek data base, and six (1.5%) of the isolates (Candida lusitaniae, 1; Candida parapsilosis, 1; Cryptococcus uniguttulatus, 1; H . anomala, 1; Torulopsis candida, 2) were misidentified by the Vitek system . Overall, the efficacy of the Vitek system compares favorably with that of the API 20C in the identification of clinically important yeasts.

Rev Med Brux, 1990 Sep, 11(7), 278 - 82
{Current progress in antifungal therapy: the value of fluconazole}; Meunier F; Invasive fungal infections are major problems in immunocompromised patients and optimal therapeutical modalities are still far from optimal . Recently, progresses of antifungal therapy have been achieved with the development of new antifungal agents . In particular, fluconazole seems very promising due to the availability of oral and intravenous formulations . Tolerance and compliance of patients are excellent and side effects as well as interaction with other drugs are less commonly observed than with other antifungal agents available so far . The major indications of fluconazole are candidiasis and cryptococcosis.

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