Cryptococci

Surv Ophthalmol, 1987 May-Jun, 31(6), 384 - 410
Acquired immunodeficiency syndrome (AIDS); Schuman JS et al.; The Acquired Immunodeficiency Syndrome (AIDS), caused by the human immunodeficiency virus (HIV), also called the human T-lymphotropic virus type III/lymphadenopathy-associated virus {HTLV-III/LAV}, has affected over 23,000 people; more than half of those with the disease have died . The actual case fatality rate approaches 100% . AIDS affects all groups and classes of people, although some are at special risk . Distribution of the disease is worldwide . The illness' effects on the body are widespread; of special interest are the ophthalmologic manifestations . The eye may be infected by various viruses (cytomegalovirus, varicella-zoster virus, herpes simplex virus or HIV itself), toxoplasma gondii, candida sp, cryptococcus neoformans, M . tuberculosis, or M . avium-intracellulare . Kaposi's sarcoma may affect the eye as well . Retinal vascular abnormalities (e.g., cotton-wool spots, vasculitis) are not uncommon in AIDS . The syndrome may present with neuro-ophthalmologic manifestations . No effective treatment for the illness is currently available, although several hold promise and there is hope for an AIDS vaccine . Prevention of infection through reduction of risks appears to be the only defense against AIDS at this time.

Can J Microbiol, 1987 May, 33(5), 396 - 404
Urease testing and yeast taxonomy; Booth JL et al.; When urease production was assayed by the hydrolysis of {14C}urea, all basidiomycetous yeasts tested, including the Cryptococcus vishniacii complex (previously reported urease negative), produced significant amounts of 14CO2 . The Schizosaccharomycetaceae were the only urease-positive ascomycetous yeasts tested . Yarrowia lipolytica was urease negative . The stoichiometry of {14C}urea hydrolysis paralleled by Roberts' rapid urea hydrolysis (RUH) test indicated that causes of anomalous results in conventional urease testing include acidification and alkalinization of the test medium by products of endogenous metabolism and autolysis rather than urease activity . Anomalous results also occurred when cells were grown on media containing the chelating agent ethylenediaminetetraacetic acid (EDTA) prior to RUH . The addition of EDTA to a complex natural medium inhibited urease production in all yeasts reportedly growing at 35 degrees C (and all other yeasts tested), except Filobasidiella (Cr.) neoformans var . neoformans (NIH 12) . The RUH test could differentiate at the varietal level: Fil . (Cr.) neoformans var . neoformans was about 10 times more resistant to EDTA in media used for the growth of cells prior to RUH testing than was Fil . neoformans var . bacillispora (Cr . neoformans var . gattii) (NIH 191) . Urease production by Fil . neoformans var . bacillispora was specifically restored to half maximal activity by the addition of 22 microM Ni+2 (as NiCl2) to a growth medium containing 0.100 mM EDTA.

Antimicrob Agents Chemother, 1987 May, 31(5), 834 - 6
Activity of phenothiazines against medically important yeasts; Eilam Y et al.; Two phenothiazine compounds, trifluoperazine and chlorpromazine, inhibited growth in vitro of the five most common pathogenic yeasts, with MICs ranging from 10 to 40 micrograms/ml . Daily intraperitoneal injections of trifluoperazine (4 to 7 mg/kg of body weight) increased the survival of mice experimentally infected with Candida albicans or Cryptococcus neoformans . The potential use of these drugs against fungal meningitis is discussed.

J Antimicrob Chemother, 1987 May, 19(5), 663 - 70
Efficacy of fluconazole (UK-49,858) against experimental aspergillosis and cryptococcosis in mice; Troke PF et al.; The efficacy of fluconazole, a new bis-triazole antifungal agent, was compared with that of orally administered ketoconazole and parenterally administered amphotericin B against aspergillus and cryptococcus infections in mice . Fluconazole was 5-20-fold more active than ketoconazole against systemic aspergillosis and against systemic, intracranial and pulmonary cryptococcosis but was less active than amphotericin B.

S Afr Med J, 1987 Apr 18, 71(8), 510 - 2
Sensitivity and specificity of a latex agglutination test for detection of cryptococcal antigen in meningitis; Coovadia YM et al.; A cryptococcal latex agglutination test (Crypto-La; International Biological Laboratories, Canbury, New Jersey, USA) was evaluated for its ability to detect cryptococcal antigen in cerebrospinal fluid (CSF) specimens obtained from black patients with a clinical diagnosis of meningitis . Of the 445 Gram-stained and bacterial culture-negative CSF specimens routinely tested for cryptococcal antigen, 34 (7,6%) were positive . With the exception of 1 false-positive result, the remaining 33 specimens were obtained from 12 patients in whom the diagnosis of cryptococcal meningitis was confirmed by the isolation of Cryptococcus neoformans . The Crypto-La test gave false-positive results on 1% (4/384) of control CSF specimens tested . Nonspecific agglutination reactions were observed with 1,6% (13/829) of all CSF specimens and 22% (10) of sera tested . The ethylenediaminetetra-acetic heat-extraction method proved reliable in eliminating false-positives and nonspecific agglutination reactions in CSF and serum specimens.

Br Med J (Clin Res Ed), 1987 Apr 4, 294(6576), 868 - 9
From persistent generalised lymphadenopathy to AIDS: who will progress?
Carne CA, Weller IV, Loveday C, Adler MW.
PIP: The current rate of progression of persistent generalized lymphadenopathy to acquired immunodeficiency syndrome (AIDS) was tested in a cohort of 105 homosexual men in London, UK . 5 patients were lost to follow-up, and the remaining 100 were seen every 3 months . All tested positive for the human immunodeficiency virus antibody . Previous clinical observations had shown oral candida; anemia; leucopenia; thrombocytopenia; enthrocyte sedimentation rate 15 mm in the 1st hour to be possible predictors of AIDS . 5 of the 13 patients who developed AIDS during a mean follow-up period of 22 months (range 12-32) developed Pneumocystis carinii; 5 Karposi's sarcoma; 1 both; 1 P carinii and cryptosporidiosis; and 1 cryptococcal meningitis . A life table technic calculation showed that over 3 years the probability of patients with persistent generalized lymphadenopathy progressing to AIDS was 20.9% . Of the clinical features examined, those most likely to indicate progression to AIDS were Oral candida (relative risk (RR)=12); Lymphopenia (RR=7); Erythrocyte sedimentation rate 15mm (RR=7); and anemia (RR=6) . There were figures for median time before AIDS onset and the range of variation of these median times for these symptoms, e.g . oral candida, 8 months median; range of 1-24 months . Similar prospective studies performed in the US are reviewed . It is determined that a clinical examination and hematological measurements are useful in determining progression risk .

Leukemia, 1987 Apr, 1(4), 288 - 93
Unusual presentations and complications of hairy cell leukemia; Bouroncle BA; In a series of 116 patients with hairy cell leukemia at the Ohio State University, followed for over 20 years, several unusual presentations and complications were encountered . The awareness of these unusual findings might be of help to investigators in the prompt diagnosis and treatment of this disease . The patients presented had, at the time of initial diagnosis, spontaneous rupture of spleen, cryptococcal meningitis, massive splenomegaly with hairy cell infiltration with normal peripheral blood and bone marrow examination, and marked leukocytosis . Some patients developed unusual complications during the course of their illness, such as gastric submucosal infiltration by hairy cells with secondary protein-losing enteropathy, spinal cord compression with paralysis, esophageal perforation with fistula tract, and massive ascites and pleural effusion with typical hairy cells present in the ascitic and pleural fluid.

South Med J, 1987 Apr, 80(4), 511 - 3
Cryptococcemia due to Cryptococcus albidus; Gluck JL et al.; We have described a patient with cryptococcemia due to Cryptococcus albidus . Although usually nonpathogenic, C albidus and other non-neoformans cryptococcal species may occasionally be the causative agents in severe infections in man . The latex agglutination test for cryptococcal polysaccharide capsular antigen appears to be specific for C neoformans and thus may be falsely negative in serious infections caused by non-neoformans cryptococci, as seen in our patient with C albidus fungemia . Severe infections caused by C albidus appear to respond to treatment with amphotericin B with or without 5-fluorocytosine but so few cases are available for analysis that no firm conclusions can be made in this regard at present.

Q J Med, 1987 Apr, 63(240), 283 - 95
Chronic meningitis without predisposing illness--a review of 83 cases; Anderson NE et al.; Eighty-three previously healthy patients with chronic meningitis presenting to a general hospital were reviewed . The single most common cause was tuberculosis (40 per cent) with cryptococcosis (7 per cent), malignancy (8 per cent) and other definable causes much less frequent . In one-third of patients (34 per cent) no cause was found although most appeared to respond to treatment either with anti-tuberculosis drugs or steroids . There were some differences in clinical presentation, the clinical picture being most characteristic in tuberculous meningitis and malignant meningitis . However, there were frequent exceptions to any general rule and, particularly in adults, the clinical features and changes in cell count, protein and glucose in the cerebrospinal fluid (CSF) did not reliably distinguish one form of chronic meningitis from another . Cerebral and meningeal biopsy produced disappointing results with respect to practical guidance in management . It is often necessary to begin treatment before a cause has been identified . Important points in management include the early use of anti-tuberculosis treatment and the difficulty in deciding on a trial of treatment with corticosteroids or amphotericin B . Not emphasised in previous reports is a subgroup of patients with idiopathic chronic meningitis who are responsive to treatment with steroids . Those patients tend to follow a more prolonged indolent course and often require long-term immunosuppression to control symptoms.

Med Trop (Mars), 1987 Apr-Jun, 47(2), 185 - 8
{Salmonella bacteremia and generalized cryptococcosis, a double indicator of African AIDS}; Rogerie F et al.; PIP: This work argues that nontyphoidal Salmonella bacteremia should be included in the provisional World Health Organization case definition of adult AIDS for countries with limited diagnostic resources . The case is described of a 50-year-old-man from Rwanda with proven AIDS who died from generalized cryptococcosis 6 months after episodes of recurrent fever during which Salmonella enteritidis was isolated from blood cultures . 3 months after the initial hospitalization with Salmonella bacteremia a positive hemoculture for Cryptococcus neoformans was obtained, and subsequent ELISA and immunofluorescence tests for AIDS were positive . Adult nontyphoidal Salmonella septicemia affects weakened subjects suffering from deficits of cellular immunity: leukemia, lymphoma, malignant tumors, or treatment with corticoid or other immunosuppressive medications . Numerous publications have drawn attention to the association of Salmonellosis and AIDS . Most of the authors observed the salmonelloses in AIDS patients were recurrent, and some recommended uninterrupted antibacterial treatment for such cases . Several authors mentioned the early character of Salmonella, which often appeared before the 4 opportunistic infections recognized in the WHO definition of AIDS .

J Med Vet Mycol, 1987 Apr, 25(2), 67 - 76
Immunosuppression in experimental cryptococcosis in rats . Induction of afferent T suppressor cells to a non-related antigen; Sotomayor CE et al.; To demonstrate the nature of the suppressor cells elicited in rats infected with Cryptococcus neoformans and immunized with human serum albumin (HSA), spleen mononuclear (SpM) cells were fractionated through a nylon wool column . The adherent and non-adherent populations were collected and transferred to syngeneic rats . In all cases, the non-adherent or T-enriched cells adoptively transferred suppression to HSA, however, the suppressive effects of the non-adherent cells were never as great as those of the unpassed population of SpM cells . The fractions adherent to nylon wool also diminished the delayed-type hypersensitivity response to HSA although this was not significant, but glass-adherent cells did exhibit significant suppressor activity . Immunized, non-infected rats were used as donor controls . Furthermore, we showed that the T-enriched-cells are sensitive to treatment with low doses of cyclophosphamide and that they bind HSA . These data indicate that immune suppression of the induction of the delayed-type hypersensitivity response to HSA in cryptococcosis can occur as a result of infection with C . neoformans, and that at least one mechanism involved is the induction of adherent and non-adherent suppressor cells . Characterization of the non-adherent cells indicates that they are Ts1 cells.

Am J Med, 1987 Mar 23, 82(3 Spec No), 665 - 7
Cryptococcal peritonitis . Report of a case and review of the literature; Poblete RB et al.; Cryptococcus neoformans is a rare cause of peritonitis; only four cases have been reported in the literature . A 63-year-old man in whom isolation of C . neoformans from ascitic fluid provided the initial clue to disseminated cryptococcosis is described . Review of this case and those previously reported reveals striking association between cryptococcal peritonitis and hepatic disease.

Chest, 1987 Mar, 91(3), 459 - 61
Pleural cryptococcosis in the acquired immune deficiency syndrome; Newman TG et al.; Pleural cryptococcosis is extremely rare . We report the first case of cryptococcal pleural effusion in association with the acquired immune deficiency syndrome . Pleural effusion without the evidence of pulmonary parenchymal involvement was the initial and only clinical finding leading to the diagnosis of disseminated cryptococcosis . The pleural effusion resolved spontaneously prior to amphotericin B therapy.

Infection, 1987 Mar-Apr, 15(2), 87 - 92
Problems in antifungal chemotherapy; Stevens DA; The field of antifungal chemotherapy is undergoing rapid change at present, with an accelerating pace of introduction of new agents . The problems at present include the need for more effective agents, particularly with novel modes of action . Fungal infection must be considered more frequently in differential diagnosis, and methods developed for early diagnosis . The literature must be improved, with more precise terms . Trials comparing agents are needed, as are studies directed at determining the appropriate length of therapy . In vitro susceptibility testing must be standardized, and clinical correlations examined . Particular problem areas in current therapy are deep candida infections, zygomycotic infections, fungal endocarditis and meningitis, cryptococcosis in AIDS patients, and ocular infections with Fusarium species . Immunomodulating or "pro-host" drugs present an as yet unexplored avenue for clinical therapy . Regimes to prevent fungal infection need improvement . Until the needed advances occur, we must be resourceful in minimizing the toxicity of the agents presently available.

Infect Immun, 1987 Mar, 55(3), 749 - 52
Protection of mice against experimental cryptococcosis by anti-Cryptococcus neoformans monoclonal antibody; Dromer F et al.; Humoral immunity does not play a prominent role during experimental cryptococcosis . However, previous studies have shown that immunoglobulin G (IgG) anti-Cryptococcus neoformans antibodies can mediate cell-dependent yeast killing in vitro . Therefore, the protective effect of a previously described monoclonal IgG1 anti-C . neoformans antibody (E1) administered intraperitoneally 24 h before intravenous infection with a C . neoformans serotype A strain was evaluated in mice . Heavily infected (3 X 10(6) cells) untreated mice died in 2.9 +/- 0.5 (standard deviation) days . Survival time was 17.9 +/- 1.6 days for mice treated with 100 micrograms of E1 and 3.0 +/- 0.7 days for mice treated with 100 micrograms of a monoclonal IgG1 anti-thyroglobulin antibody used as a control . Protection was dose dependent and required at least 10 micrograms of E1 (mean antibody concentration in serum +/- standard deviation, 6.6 +/- 2.3 micrograms/ml) . Insufficient concentrations of IgG anti-C . neoformans antibody could explain previous negative results obtained with polyclonal immune serum . After infection with a smaller inoculum (5 X 10(3) to 5 X 10(4)), the protective effect of E1 was confirmed by the presence of fewer CFUs in the spleens and brains of treated mice than in those of controls . CFU were still detected in the brains of protected mice 5 days after infection, although soluble antigen was negative in sera . These results suggest that passive serotherapy with monoclonal IgG antibodies could participate in the prevention or treatment of experimental cryptococcosis.

Infect Immun, 1987 Mar, 55(3), 742 - 8
Production, characterization, and antibody specificity of a mouse monoclonal antibody reactive with Cryptococcus neoformans capsular polysaccharide; Dromer F et al.; Two monoclonal immunoglobulin G1 antibodies reacting with Cryptococcus neoformans capsular polysaccharide (CNPS) were produced in mice by using a carefully defined procedure for immunization with unmodified CNPS purified from C . neoformans serotype A . Since the antibodies were found to have the same pattern of specificity, only one of them (E1) is described . This anti-CNPS monoclonal antibody reacted with the glucuronoxylomannan component of CNPS but not with the constituent monosaccharides or with the mannose alpha(1----3)-linked oligosaccharide structures present on CNPS . E1 appeared to be specific for C . neoformans serotype A by agglutination of whole cells; it was specific for soluble CNPS A by gel immunoprecipitation . However, indirect immunofluorescence and competitive-binding enzyme-linked immunosorbent assay experiments showed low levels of cross-reactivity with serotypes B and D but not with serotype C . Concentrations 10,000 times higher for serotypes B and D cells than for serotype A cells were required for a 50% inhibition of E1 anti-CNPS A activity as measured by enzyme-linked immunosorbent assay . Among the other yeasts tested, a cross-reaction was only detected with Trichosporon beigelii . The four serotypes of C . neoformans could be distinguished based on intensities and patterns of fluorescence in an indirect immunofluorescence assay using the monoclonal anti-CNPS A antibody . Monoclonal anti-CNPS A antibodies could be useful for fundamental studies on the glucuronoxylomannan structure, as well as for clinical applications such as serotyping and possibly the serological diagnosis of cryptococcosis.

J Clin Neuroophthalmol, 1987 Mar, 7(1), 45 - 8
Visual loss in cryptococcal meningitis; Ofner S et al.; Optic neuropathy with visual loss is a well-known complication of chronic elevated intracranial pressure . The association of visual loss with cryptococcal meningitis may reflect the intracranial hypertension often seen in this condition . However, the generally poor results of optic nerve sheath fenestration and analysis of autopsy cases have led to the suggestion that direct invasion of the visual system by organisms may be the more common mechanism of visual loss . We describe a patient with severe visual loss from cryptococcal meningitis in whom organisms were demonstrated in the optic nerve sheath obtained at the time of fenestration . This is the first report to demonstrate this finding in a living patient.

Acta Chir Scand, 1987 Feb, 153(2), 133 - 5
Fungal mastitis . Case report; Walia HS et al.; Fungal (cryptococcal) mastitis in a young woman seemed to be a systemic manifestation of the infection, since it recurred contralaterally within 4 months . Diagnostic problems are discussed . Only two previous reports of deep mammary mycosis were found . In addition to excision, ketoconazole is recommended to prevent recurrence or serious complications.

Mycopathologia, 1987 Feb, 97(2), 117 - 9
Aspergillus myositis in a patient with a myelodysplastic syndrome; Reboli AC et al.; We present the case of an elderly man who, while being treated with corticosteroids for a myelodysplastic syndrome, developed myositis of the calf due to Aspergillus fumigatus . Despite therapy with amphotericin B the myositis failed to resolve and he died . At autopsy, a localized necrotizing myositis of the right calf was found with no evidence of disseminated Aspergillus infection . Myositis in the setting of disseminated candidiasis or cryptococcosis has been previously reported . This case is unique in that it is the first reported case of localized fungal myositis and of myositis caused by Aspergillus.

J Clin Microbiol, 1987 Feb, 25(2), 430 - 1
Cryptococcus neoformans var . gattii in Australia; Ellis DH; An examination of 45 clinical isolates of Cryptococcus neoformans revealed an unusually high incidence of C . neoformans var . gattii in South Australia (65%) and in the Northern Territory (95%) . In assessing all the available data from Australian isolates of C . neoformans, there appeared to be an endemic focus for the incidence of C . neoformans var . gattii in the rural aboriginal population of the Northern Territory.

Diagn Microbiol Infect Dis, 1987 Feb, 6(2), 131 - 8
Biochemical serogrouping of clinical isolates of Cryptococcus neoformans; Shadomy HJ et al.; Three hundred twenty-three clinical isolates of Cryptococcus neoformans of diverse geographic origins were biochemically serogrouped using glycine-cycloheximide-phenol red agar (GCP), the same medium less cycloheximide (GOP), and glycine-L-canavanine bromothymol blue agar (CGB) . Twenty isolates gave positive reactions on all three media typical of the B and C serotypes . Three were from the Peoples' Republic of China; three each were from Michigan (two patients) and Louisiana; two each were from California, Georgia, and Virginia; and one each was from Alabama, Florida, North Carolina, Oklahoma, and Tennessee . Two hundred seventy-six isolates were identified as belonging to the A/D serogroup; 272 were of American origin and four were from China . Twenty-seven isolates were biochemically ungroupable . Evaluations of the reactions on all three media were open to subjective interpretations . Utilization of glycine was the most frequent atypical variable; 36 of 276 (13%) A/D isolates utilized glycine while being inhibited by either GCP or CGB or both . Significant differences between A/D and B/C serogroups in terms of susceptibility to 5-fluorocytosine but not to amphotericin B were observed; B/C serogroup isolates appeared to be less susceptible to 5-fluorocytosine in vitro than were the A/D serogroup isolates . These results provided new evidence on the distribution of B/C serogroup isolates of C . neoformans in America and demonstrate the difficulties of using biochemical tests for serotyping purposes . They also offer a possible explanation for the apparent more refractory therapeutic responses of infections caused by B and C serotypes to conventional antifungal chemotherapy.

Lancet, 1987 Jan 3, 1(8523), 1 - 4
Laboratory testing on cerebrospinal fluid . A reappraisal; Hayward RA et al.; 555 consecutive cases in which cerebrospinal fluid (CSF) was sent for cell count were reviewed to determine which cerebrospinal-fluid tests affect diagnosis or therapy . Among 334 cases (60%) with a normal opening pressure, cell count, and protein, 1385 additional tests were done, but such tests were useful in only 3 patients (0.9%) with multiple sclerosis . Among 148 consecutive cases of bacterial, chronic infectious, and malignant meningitis the opening pressure, cell count, or protein was abnormal in all but 3 (2 childhood bacterial meningitis and 1 cryptococcal meningitis in a patient with the acquired immunodeficiency syndrome) . If the opening pressure, cell count, and protein are normal, no additional CSF tests are needed in most instances; however, in immunocompromised patients and in those with possible multiple sclerosis or childhood bacterial meningitis additional tests may be indicated.

Neuroradiology, 1987, 29(1), 43 - 6
Cryptococcus meningitis, clinical--CT scan considerations; Tan CT et al.; Twenty adult cases of cryptococcus meningitis and their cranial CT scan findings were reviewed . Ten patients had abnormal CT scans . The findings were hydrocephalus, gyral enhancement, focal nodules, decreased attenuation in the white matter, and patchy increased uptake of contrast . The CT scan appearance often failed to correspond with symptoms . None of the appearances was specific to the cryptococcal infection . Fourteen patients developed papilloedema during the course of the illness . The majority of the patients who developed papilloedema did not have demonstrable hydrocephalus.

Am J Med, 1987 Jan, 82(1), 149 - 50
Acquired immune deficiency syndrome presenting as bone marrow and mediastinal cryptococcosis; Witt D et al.; Disseminated cryptococcosis developed as the first manifestation of the acquired immune deficiency syndrome in a previously healthy Haitian man . Following presentation with a febrile illness that included massive mediastinal and peripheral lymphadenopathy, the patient died of overwhelming pulmonary, visceral, and meningeal cryptococcosis.

Clin Exp Neurol, 1987, 23, 127 - 37
Cryptococcal infections of the central nervous system: a ten year experience; Waterston JA et al.; Twenty cases of cryptococcal CNS infection treated at the Alfred and Fairfield Infectious Diseases Hospitals from 1975 to 1985 were reviewed . A predisposing immunological deficit was present in 40% of the cases and nearly half had evidence of pulmonary involvement . Severe headache was an almost universal presenting feature but fever and meningismus were not . Measurement of CSF cryptococcal antigen and CSF culture were far more reliable diagnostic markers than Indian ink smears . Cerebral CT scanning identified abnormalities in nearly 30% of cases, including 2 with cystic lesions and 2 with mass lesions . Combination therapy with amphotericin B and 5-fluorocytosine was used as first line treatment . Ventricular shunts were required for 2 patients with hydrocephalus, and persistently raised intracranial pressure often required frequent lumbar punctures and corticosteroids for control . Mortality was 30% and correlated with the presence of impaired conscious state, hydrocephalus or other neurological deficit, underlying immunodeficiency and low CSF glucose levels.

Rev Neurol (Paris), 1987, 143(4), 290 - 3
{Quasi-normal cerebrospinal fluid in patients with acquired immunodeficiency syndrome and cryptococcal meningitis}; Gudesblatt M et al.; We report eight patients with cryptococcal meningitis and a cerebrospinal fluid characterized by few or no white blood cells and chemistries that may be near normal . In four of these patients, only testing for cryptococcal antigen allowed the initial diagnosis . Seven of the patients had a certain diagnosis of AIDS . Six have died . Autopsies performed in two cases indicated a poor meningeal inflammatory response . Contrary to the findings in most immunodeficient patients, in AIDS cryptococcal meningitis may present with few cellular or biochemical abnormalities in the cerebrospinal fluid . In AIDS patients presenting with headache and fever or change in mental status, examination of the cerebrospinal fluid should not be limited to routine studies.

Ann Pathol, 1987, 7(1), 15 - 24
Acquired immune deficiency syndrome (AIDS) in Brazil . Necropsy findings; Michalany J et al.; PIP: Clinical and autopsy findings obtained from 15 male patients treated for acquired immunodeficiency syndrome (AIDS) at 3 hospitals in Sao Paulo provided a clearer profile of AIDS cases in Brazil . Of the 12 patients whose sexual orientation was recorded, 9 were homosexual and 3 were bisexual . 75% were between the ages of 22-36 years; 14 were white . The duration of diseases ranged from 14 days-7 months in this series, confirming the rapid evolution of AIDS from 1st symptom to death . The most common clinical manifestations of disease were fever, cough, weight loss, diarrhea, and lymphadenopathy . Organs most frequently involved were the lungs (13 cases) and encephalum (9 cases) . Microscopic findings revealed 9 types of microorganisms, fungi, and protozoa, the most common of which was Cytomegalovirus (7 cases) . The cause of death was meningoencephalitis in 7 cases and panlobar pneumonia in 3 cases . The incidence of Kaposi's sarcoma (2 cases) was surprisingly low in this series . In addition to lesions produced by microorganisms, there were important associated lesions represented by lymphocytic depletion, acute myocarditis, brown atrophy of neuronia, acute pancreatitis, and liver cirrhosis . Several microorganisms and tumors in these AIDS patients were discovered only at autopsy, confirming the importance of necropsy to the study of the natural history of this disease . An unexpected pathological finding in this series was the absence of cellular reactions to microorganisms, particularly Pneumocystis carinii, Cryptococcus neoformans, and Mycobacterium tuberculosis .

J Med Primatol, 1987, 16(1), 39 - 47
Spontaneous cryptococcosis of a squirrel monkey (Saimiri sciureus) in French Guyana; Roussilhon C et al.; An old female squirrel monkey (Saimiri sciureus) with a tumor-like growth of the lower jaw died in shock after 2 months of illness . Histological studies of different tissue samples demonstrated that the pathological agent was Cryptococcus . Multiple foci of fungus existed in the thoracic cavity with essentially pulmonary and glandular localizations.

Mycopathologia, 1987 Jan, 97(1), 9 - 16
Description of a case of rhinosporidiosis in Spain; Alonso MJ et al.; Rhinosporidiosis is reviewed, and the first autochthonous case in Spain is presented (site: in the nasal cavity of a 19-year-old male from a rural background) . Diagnosis was established morphologically after eliminating the possibilities of Cryptococcus neoformans, Coccidioides immitis, and Chrysosporium crescens . Clinico-pathological features are described . Preparations were stained with hematoxylin-eosin, PAS, and methenamine silver, and studied for fluorescence . Certain aspects of the epidemiology and diagnosis are commented upon.

Histopathology, 1987 Jan, 11(1), 9 - 20
Fungal and nocardial infections of the kidney; Raghavan R et al.; This report describes 16 cases of candidiasis, seven of aspergillosis, four of mucormycosis, two of cryptococcosis and one of nocardiosis in which the kidney was involved . Characteristic patterns of renal tissue injury were seen in each of these infections . Candida and nocardia caused microabscesses in the cortex and medulla . Tissue destruction was minimal with candidiasis and when present was confined to the papillary tips and produced only mild impairment of renal function . Aspergillus and mucor invaded blood vessels resulting in thrombosis and extensive necrosis of cortical and medullary tissue and most patients had clinical and biochemical evidence of renal disease . Cryptococcosis caused no tissue reaction or clinically evident renal disease in the two immunosuppressed patients studied.

Mycopathologia, 1987 Jan, 97(1), 25 - 31
Evaluation of SOC for the presumptive identification of Candida albicans and Cryptococcus neoformans; Fleming WH 3rd et al.; SOC, a fungal growth medium composed of Solryth, oxgall, and caffeic acid, was evaluated as a medium to provide rapid, differential identification of Candida albicans and Cryptococcus neoformans . Using a variety of common isolation media to produce the yeast inocula, the germ tube methods tested ranked in the following order of decreasing sensitivity: SOC (97% +/- 1), serum (92% +/- 5), rabbit coagulase plasma with EDTA in combination with tryptic soy broth (89% +/- 5), TOC (89% +/- 6), and rabbit coagulase plasma with EDTA (83% +/- 4) . In chlamydospore production, SOC also proved to be the most sensitive after 24 h incubation: SOC (96% +/- 2), TOC (80% +/- 2), and cornmeal-Tween 80 agar (14% +/- 3) . Other medically important yeasts showed normal patterns of growth within 24 h on SOC, thus assisting in their identification . Eighty strains of Cryptococcus neoformans showed characteristic brown pigmentation on SOC and TOC within 18 h, while all other species of the genus Cryptococcus and 229 Candida isolates did not show a change in pigmentation.

Crit Rev Microbiol, 1987, 14(2), 99 - 170
The genetics of medically important fungi; Whelan WL; The present review is concerned with recent progress in basic genetic investigations with a variety of fungi which are pathogenic for man and animals . The principles and strategies involved in undertaking genetic investigations of sexual species and of asexual species are discussed . Progress in genetic analysis of Cryptococcus neoformans made possible by the discovery of its sexual phase is described in detail, as is progress in development of parasexual methods of analysis in Candida albicans . The genetic bases of virulence and drug resistance are discussed for those few species in which these phenotypes have been investigated . Suggestions for future research, including the application of recent advances in molecular biology to the study of pathogenic fungi, are presented.

J Am Acad Dermatol, 1987 Jan, 16(1 Pt 2), 243 - 9
Localized cutaneous cryptococcosis successfully treated with ketoconazole; Granier F et al.; A 27-year-old female recipient of a renal allograft, treated with systemic steroids and azathioprine, developed progressive cutaneous lesions (an ulcer, a nodule, and an abscess) . Histopathologic and tissue-culture examination of the skin lesions led to the diagnosis of cutaneous cryptococcosis . A description of the light and electron microscopic features of the cutaneous lesions is reported . A thorough visceral investigation failed to detect systemic involvement . The patient was treated with oral ketoconazole (400 mg daily) for 6 months . A gradual healing of the lesions was obtained, and cultures performed 3 months after the onset of treatment failed to show Cryptococcus neoformans . No relapse or dissemination has so far been observed.

Rev Infect Dis, 1987 Jan-Feb, 9 Suppl 1, S4 - 14
Evolution of antifungal agents: past, present, and future; Drouhet E et al.; Important progress has been achieved in antifungal chemotherapy in recent years . Two groups of drugs are now used: those produced by various organisms and those made synthetically . In the first group, only amphotericin B (1956) administered systemically is active in numerous deep mycoses . Although toxicity limits the use of amphotericin B, it is still the drug of choice for systemic mycoses . Griseofulvin was the first agent used for oral treatment of dermatophytoses . The introduction of flucytosine began a new era in chemotherapy; however, although flucytosine is orally administered and rapidly distributed, its antifungal activity is limited to cryptococcosis and systemic candidosis . The rapid induction of flucytosine-resistant mutants led to the development of treatment regimens of amphotericin B plus flucytosine . With the development of imidazole derivatives in 1969, a new generation of azole antifungal agents has emerged . Of these, only ketoconazole was orally active . New azole derivatives and triazoles have been synthesized, but only itraconazole has been successful in the treatment of superficial and deep mycoses in humans . Future trends for the development of agents with fungicidal activity, wider spectra, and better distribution are proposed . The association of immunotherapy with antifungal chemotherapy may offer new treatments for fungal infections in immunocompromised patients.

Arch Pathol Lab Med, 1987 Jan, 111(1), 53 - 7
Advantage of Fontana-Masson stain in capsule-deficient cryptococcal infection; Ro JY et al.; We describe light and electron microscopic findings in three cases of pulmonary infection caused by capsule-deficient Cryptococcus neoformans (CDCN) and emphasize the value of the Fontana-Masson silver (FMS) stain in diagnosing cryptococcosis . Capsule-deficient C neoformans infections, including coccidioidomycosis, histoplasmosis, typical cryptococcosis, blastomycosis, candidiasis, and pneumocystosis were used as controls . Several stains including mucicarmine, alcian blue, and FMS were done on tissue sections from all of the above mentioned infections . It was found that while the FMS stain was positive only in the organisms of CDCN and typical C neoformans, the mucicarmine was positive only in typical C neoformans . The negativity of the mucicarmine in the organisms of CDCN reflected the absence of capsular material as demonstrated by ultrastructural study . Therefore, when fungal cultures are not available or are negative, and tissue mucicarmine is negative, the FMS stain is a valuable alternative for use on tissue sections . It may be used, along with routine fungal stains, when a yeast-forming fungal infection is suspected.

Retina, 1987 Summer, 7(2), 75 - 9
Cryptococcal chorioretinitis and endophthalmitis; Henderly DE et al.; The diagnosis of endogenous ophthalmic fungal infection may be difficult . A patient initially presented with hydrocephalus and later developed a progressive bilateral intraocular inflammation unresponsive to corticosteroids or antituberculous therapy . Further evaluation with vitreous biopsy study and lumbar puncture led to the diagnosis of cryptococcal chorioretinitis, endophthalmitis, and meningitis . Initial treatment with intravenous amphotericin failed to control the intraocular infections . Vitrectomy and intravitreal injections of amphotericin combined with the systemic intravenous amphotericin halted progression of the intraocular disease . This case demonstrates the difficulty in making the diagnosis of an endogenous fungal endophthalmitis and the value of diagnostic vitreous biopsy study in cases of increasing intraocular inflammation unresponsive to medical therapy . It also suggests the usefulness of vitrectomy combined with intravitreal amphotericin in cases of fungal endophthalmitis that are unresponsive to systemic antifungal agents.

Am J Med, 1987 Jan, 82(1), 129 - 31
Disseminated cryptococcal infection in a patient with hypogammaglobulinemia and normal T cell functions; Gupta S et al.; The immunologic status of a patient with disseminated cryptococcosis and no underlying predisposing factor was evaluated . The proportions and numbers of T cells, T cell subsets, B cells and proliferative responses to mitogens and soluble antigens, including cryptococcal antigen, were comparable to those in healthy control subjects; however, the patient had moderately severe hypogammaglobulinemia . The patient continues to do well clinically with intravenous gammaglobulin and antifungal therapy . This study suggests that antibodies might also play a role in the defense against cryptococcal antigen.

Ann Med Interne (Paris), 1987, 138(8), 607 - 9
{Adrenal lesions in AIDS: anatomopathological study}; Bricaire F et al.; Systematic autopsy studies of 100 patients with AIDS confirmed a high incidence of adrenal lesions . Eighty eight cases were analysed, 79 men and 9 women; 57 had opportunist infection alone, 6 had Kaposi sarcomas and 30 had an association of both pathologies . The adrenal glands were normal in 19 cases and abnormal in 64 cases . One case has non-specific spongiocytic depletion and 4 were uninterpretable because of necrosis . The main adrenocortical changes were inflammatory (N = 37) or necrotic (N = 22) . The commonest sites were in the adrenal medulla in the cortex or at the cortico-medullary junction . There was a high incidence of cytomegalic inclusion bodies (44 cases) . In 7 cases specific lesions were observed; cryptococcus (1), toxoplasmosis (1), tuberculosis (2), Kaposi (3) . Adrenal insufficiency was diagnosed before death in only 3 cases.

Ann Biol Clin (Paris), 1987, 45(5), 588 - 90
{Significance of the presence of Candida sp . in bronchopulmonary secretions . Contribution of pulmonary biopsy}; Roux P et al.; Candida SP is often found in broncho-pulmonary secretions (expectorations, bronchial aspirations, bronchiolo-alveolar lavage...); however, its presence even in massive amounts, is difficult to interpret . Is it a sign of broncho-pulmonary candidosis or mouth-pharynx contamination? The different clinical and biological elements, in particular immunology in immunodepressed patients, bring little information . In this article, we present the retrospective study of 18 patients hospitalized in Pneumology Department of Tenon Hospital for severe extensive pneumopathy of unexplained origin . In these patients, for the most part immunodepressed, Candida sp was found in large amounts in at least a sample (expectorations {5} and/or bronchial aspirations {4} and/or bronchiolo-alveolar lavage {12} . No lesion suggestive of candidiasis was found during bronchial endoscopy carried out for these different samples . In pulmonary biopsy with diagnostic in view, these yeasts were found only in one patient . In this patient, as C . tropicalis was associated with Pneumocystis carinii and Cryptococcus neoformans, it was difficult to know the respective part of each of these agents in pulmonary symptomatology . In the other 17 cases, the direct examination and cultures were negative . The presence of Candida sp in the different broncho pulmonary secretions is not synonymous of bronchopulmonary candidiasis; likely it is, in most cases, a sign of contamination of mouth-pharynx origin.

Rev Neurol (Paris), 1987, 143(10), 631 - 42
{Neuropathological study of 31 cases of acquired immunodeficiency syndrome}; Henin D et al.; Post-mortem study of every patient who died from AIDS in Pitie-Salpetrire Hospital from June 1984 to November 1985 was performed without regard to the presence of neurological signs and symptoms . Autopsy were performed in 31/48 cases . Patients had been hospitalized in the Departments of Parasitology-Infectious Disease (24 cases) Internal Medicine (4 cases) and Neurology (3 cases) . In every case, formalin-fixed material from the brain and the spinal cord were embedded in paraffin (20 samples), stained with hematoxylin-eosin, PAS, Alcian blue, Giemsa, Grocott and Ziehl techniques and Bodian's silver impregnation along with Luxol fast blue, and, in celloidin (8 samples), stained with hematoxylin-eosin and Loyez' impregnation . There were 30 men (27 caucasian, 1 egyptian, 1 haitian, 1 senegalese) and one woman (congolese) . Twenty eight (28) patients were homosexuals . AIDS was transfusion-associated in two cases . Neurologic complications revealed the disease in 2 cases . Eighteen (18) patients had neurological signs or symptoms before death . Age range at death was 22-58 (mean 38) . Brain weight in AIDS (from 1150 gms to 1750 gms-mean 1428 gms) was not statistically different from the mean weight of 100 male patients in the same age range autopsied in the same laboratory during the identical period (mean 1427 gms, standard deviation: 23) . Microscopic abnormalities were present in every brain examined . These included non-Hodgkin lymphoma (3 cases), opportunistic infections (21 cases: 13 toxoplasmosis, 4 cytomegalovirus encephalitis, 3 cryptococcal meningitis, 1 infection by mycobacterium avium-intracellulare), and subacute encephalitis (17 cases, 9 isolated, 8 associated with other disorders) . The characteristic changes consisted of lympho-monocytic focal infiltrates (so-called microglial nodules) and mild lympho-monocytic perivascular cuffs in 10 cases . Typical giant cells were seen only in one case . Mild demyelinating changes were also seen in only one case . No spinal cord spongiosis, nor Progressive Multifocal Leukoencephalopathy was found . HIV localization was performed on frozen sections utilizing in situ hybridization techniques (2 cases) and immunohistologic techniques (5 cases) . HIV, RNA and proteins, was detected in 2 cases with subacute encephalitis . Infected cells were labeled with macrophage markers, and rarely with T4 lymphocyte markers . Infected astrocytes (identified by anti-GFAP serum) or neurons (identified by anti-NSE serum) were never observed . No giant cells were seen in these two cases.

Crit Rev Microbiol, 1987, 15(1), 45 - 56
The genetic basis of resistance to 5-fluorocytosine in Candida species and Cryptococcus neoformans; Whelan WL; In terms of genetically determined susceptibility to the clinical antifungal agent 5-fluorocytosine (5-FC), Candida albicans may be homozygous sensitive (FCY/FCY), homozygous resistant (fcy/fcy), or heterozygous (fcy/FCY) . Although heterozygotes are only slightly resistant, they occur at significant frequency among clinical strains and carry preexisting resistance determinants which may be responsible, following homozygosis, for treatment failures . There are two resistance genes (FCY1 and FCY2) known . Resistance in fcy1/fcy1 strains was associated with decreased UMP pyrophosphorylase activity, whereas resistance in fcy2/fcy2 strains was associated with decreased cytosine deaminase activity . These results were confirmed and extended in a 19F nuclear magnetic resonance study of 5-FC uptake and metabolism in genetically defined strains . By means of hybridization via spheroplast fusion, a complementation test was devised to test allelism of resistance determinants . Resistance to 5-FC was employed as a useful genetic marker in basic studies . In tetraploid hybrids which bore appropriate fcy markers, it was possible to select for reduction in ploidy by selecting for increased resistance to 5-FC; a novel parasexual system was thus generated (2n x 2n----4n----2n) . In linkage studies, the gene FCY1 was shown to be linked to the gene HIS . Reciprocal mitotic recombination was demonstrated repeatedly with fcy1 and his alleles in cis and in trans configurations and evidence for nonreciprocal recombination (mitotic gene conversion) was also obtained . In Cryptococcus neoformans, mutation in either of two genes (FCY1, FCY2) is sufficient to confer resistance . These genes behave as simple Mendelian determinants which recombine freely . Diploid C . neoformans heterozygous for resistance (FCY/fcy) provided useful strains in which to develop genetic mapping methodology based on mitotic recombination.

Microbiol Immunol, 1987, 31(5), 449 - 60
Evaluation of the experimental pathogenicity of some Cryptococcus species in normal and cyclophosphamide-immunodepressed mice; De Bernardis F et al.; The pathogenic potential of distinct Cryptococcus species has been evaluated in mice rendered leukopenic by one or two injections of the potent immunosuppressive drug cyclophosphamide (Cy) . Pathogenicity assessment included enumeration of viable cryptococcal cells in animal organs and histopathological observations . It was found that putatively non-pathogenic species of Cryptococcus, in particular C . cereanus and C . albidus, showed significant lethality for Cy-treated mice . In Cy-immunodepressed mice, challenged with the infectious cryptococcal cells two days after pharmacological treatment, a significant decrease of LD50 (equivalent to at least one order of magnitude) was observed for all Cryptococcus species . However, the pathogenicity enhancement due to Cy immunodepression was greater with C . neoformans . In all cases, brain and kidney were the most invaded tissues as also evidenced by histopathological examination, which showed the typical cystic lesion . All the observations made point to the conclusion that the pathogenic potential, for the immunomodulated host, of Cryptococci other than C . neoformans is significant being quantitatively and not qualitatively different from that of C . neoformans, as evidenced by a similar organotropism and similar type of histological lesions in the target organs (brain and kidney).

Trop Geogr Med, 1987 Jan, 39(1), 67 - 9
Recurrent meningitis of 5 years duration due to Cryptococcus neoformans; Woo E et al.; A patient with recurrent meningitis over five and a half years due to Cryptococcus neoformans is reported . The relapsing course and the unusual diagnostic features are emphasized.

Am J Surg Pathol, 1987, 11 Suppl 1, 3 - 15
Tissue diagnosis of selected AIDS-related opportunistic infections; Rotterdam H; Opportunistic infections are the most common initial manifestations of AIDS and, in many instances, are first encountered in surgical specimens . Pneumocystis carinii pneumonitis is by far the most frequent infection seen in biopsy specimens of AIDS patients . Most pathologists are familiar with its histopathologic presentations from previous experience . By contrast, many other opportunistic infections are either new or present clinically and pathologically in unfamiliar ways . Cytomegalovirus affects primarily the alimentary tract and lung . Colitis is the most common presentation . Penetrating ulcers may perforate . Most often, mesenchymal cells, endothelium in particular, show the typical intranuclear and intracytoplasmic inclusion bodies . The greater the number of inclusion bodies in tissues the shorter is the survival of the patient . Mycobacterium avium-intracellulare affects mainly small intestine and lymph nodes and produces a clinical and histologic picture similar to that of Whipple's disease . Diffuse infiltrates of histiocytes stuffed with acid-fast bacilli are characteristic . Cryptosporidiosis is the most ominous enteric opportunistic infection . Protozoa attach themselves to the epithelial surface and produce severe profuse, watery diarrhea . Cryptococcosis is seen in lung, lymph node, and brain biopsy specimens . Large numbers of organisms, sometimes with deficient mucinous capsules, and little or no inflammatory reaction, are notable . Toxoplasmosis is the most common cause of neurological complications in AIDS . Brain biopsy specimens show necrosis, microglial nodules, perivascular lymphocytic infiltrates, and, in 50% of cases, trophozoites.

Rev Infect Dis, 1987 Jan-Feb, 9 Suppl 1, S33 - 42
Degenerative changes in fungi after itraconazole treatment; Borgers M et al.; Changes in morphogenetic behavior and structural degeneration after exposure to itraconazole are illustrated in Candida albicans, Cryptococcus neoformans, Pityrosporum ovale, Paracoccidioides brasiliensis, Trichophyton rubrum, and Aspergillus fumigatus . With the exception of P . ovale, primary alterations are seen at the cell periphery and the cytoplasmic vacuoles in which lipid-like vesicles assemble . These changes are usually accompanied by a marked increase in cell volume, impaired cell division, or abortive hyphal outgrowth . The concentration of itraconazole necessary to induce irreversible structural degeneration (necrosis) depends greatly on the species used, the time of incubation, and the morphogenetic form in which the fungus is grown and varies from 10(-10) M (P . brasiliensis) to greater than 10(-6) M (C . albicans) . Itraconazole achieves these effects either at a concentration comparable to that required for ketoconazole (C . albicans and C . neoformans); at concentrations 10- to 100-fold lower (P . ovale, T . rubrum, P . brasiliensis), or at concentrations 100-fold lower (A . fumigatus).

Rev Infect Dis, 1987 Jan-Feb, 9 Suppl 1, S15 - 32
Activity of orally, topically, and parenterally administered itraconazole in the treatment of superficial and deep mycoses: animal models; Van Cutsem J et al.; The activity of itraconazole in vitro was evaluated for 2,094 strains of 132 fungal species, one achloric alga, nine actinomycetes, and six bacterial species . Itraconazole was active against dermatophytes (271 strains), Candida species (1,303), Cryptococcus neoformans (27), Torulopsis species (170), Pityrosporum species (40), Aspergillus species (87), Sporothrix schenckii (12), dimorphic fungi, Dematiaceae, and various other organisms . This activity depended largely on the test conditions and the medium used . Ittraconazole was as active as ketoconazole in the treatment of dermatophytoses and of both superficial and deep candidosis at oral doses about eight and four times lower, respectively, than the doses of ketoconazole required . Disseminated dermatophytosis was cured more rapidly by itraconazole than by ketoconazole . Parenteral and oral itraconazole were of equal efficacy for the treatment of systemic candidosis . Itraconazole used topically was more active than reference compounds against microsporosis, trichophytosis, and superficial candidosis . Given orally, itraconazole was effective therapy for aspergillosis and meningo-cerebral cryptococcosis in mice and for generalized cryptococcosis, histoplasmosis, and sporotrichosis in guinea pigs . No drug-related adverse effects were observed.

Am Fam Physician, 1987 Jan, 35(1), 109 - 18
Thoracic manifestations of AIDS; Hollerman JJ et al.; Of 67 hospitalized AIDS patients, 39 had pulmonary pathology . More than half of these patients died of pulmonary disease . Pneumocystis carinii, cytomegalovirus, Cryptococcus neoformans and Mycobacterium avium-intracellulare were the most common pulmonary pathogens, and Kaposi's sarcoma was the most common neoplasm . Infections and neoplasms frequently coexist in the thorax of an AIDS patient . The chest radiograph may be normal in an AIDS patient with active Pneumocystis pneumonia.

Infect Immun, 1987 Jan, 55(1), 233 - 9
Induction of a macrophage-suppressive lymphokine by soluble cryptococcal antigens and its association with models of immunologic tolerance; Blackstock R et al.; Soluble extracts of Cryptococcus neoformans were examined for their ability to induce a macrophage-regulatory T-suppressor cell known to appear in the spleens of mice infected with cryptococci . Suppressor cells were induced by injection of extracts of encapsulated or thinly encapsulated strains of cryptococci . Dose-response analysis showed that as little as 25 micrograms of soluble capsular polysaccharide antigen could induce significant suppressor cell activity, with maximum suppression occurring at a dose of 100 micrograms . The suppressor cells appeared within 1 week of injection of antigen and persisted for at least 2 months . Suppressor cells were induced in animals given tolerogenic doses of levan, human gamma globulin, and soluble capsular polysaccharide antigen . When these same antigens were administered in immunogenic form, no suppressor cell activity was detected . Therefore, the suppressive mechanism was common to models of immunologic tolerance and was not unique to cryptococcal disease or cryptococcal capsular polysaccharide antigen . The phagocytosis-inhibiting lymphokine produced by the suppressor cell population completely inhibited the phagocytic activity of only a portion of peritoneal exudate cells . Other macrophages in the population were not totally inhibited but exhibited a reduction in the number of yeast cells engulfed.

Chemotherapy, 1987, 33(5), 381 - 95
Combination therapy of experimental candidiasis, cryptococcosis, aspergillosis and wangiellosis in mice; Polak A; Combination pairs of 5-fluorocytosine (5-FC) + itraconazole (Itra), 5-FC + fluconazole (Fluc), and amphotericin B (Amph B) + Itra were administered to mice with experimental candidiasis, cryptococcosis, aspergillosis and wangiellosis with a variety of combination ratios . The life-prolonging effect of the combinations was compared with the effect of each partner administered alone and with a double dosage . Using the U test of Mann and Whitney, the effects of the concentration were classified as synergistic, additive, indifferent or antagonistic; the degree of the interaction was compared with the known effect of Amph B and 5-FC combinations . The combination 5-FC + Itra was definitely synergistic or additive in candidiasis and aspergillosis . The most pronounced synergism occurred in the infection with a 5-FC-resistant strain of Candida albicans . The degree of synergism was the same as with 5-FC + Amph B . In cryptococcosis this combination was indifferent . The combination of 5-FC + Itra merits clinical investigation, especially in candidiasis and aspergillosis . Amph B + Itra was mostly indifferent and weakly antagonistic; the degree of antagonism was significantly weaker than the one observed with Amph B + ketoconazole (Keto) . In candidiasis, 5-FC + Fluc was synergistic, but indifferent in cryptococcosis and aspergillosis.

Blood Cells, 1987, 13(1-2), 171 - 84
Mechanisms of erythroid suppression in the anemia of chronic disease; Roodman GD; The mechanism underlying the hypoproliferative anemia in patients with chronic diseases has not been clearly defined . We have examined the effects of marrow macrophages from anemic patients with chronic diseases and normals to determine if they suppress erythroid progenitors in vitro . We found that marrow macrophages from patients with the anemia of chronic disease (ACD) significantly suppressed erythroid progenitor cell growth, whereas marrow macrophages from normals did not . Since ACD is seen in conditions that activate macrophages, we then determined if activated macrophages could suppress erythroid progenitor cell growth . Peritoneal macrophages activated by chronic Cryptococcus neoformans infection significantly suppressed erythroid progenitor cell growth, although resting macrophages did not . We then examined the effects of a product of activated macrophages, tumor necrosis factor (TNF), for its effects on CFU-E and BFU-E . TNF significantly suppressed CFU-E and BFU-E growth in concentrations as low as 10(-11)-10(-12) M . Preincubation of marrow samples with TNF for as little as 15 minutes was sufficient to suppress CFU-E and BFU-E growth . Addition of TNF, after the onset of culture could only suppress CFU-E and BFU-E if added within the first 48 hours . TNF (10(-10)-10(-11) M) also inhibited the growth of hematopoietic cell lines K562, HL60, and HEL cells . These cell lines expressed low numbers of high affinity TNF receptors, with 80%-90% of the cells expressing TNF receptors.

Ophthalmology, 1987 Jan, 94(1), 23 - 6
The value of calcofluor white in the diagnosis of mycotic and Acanthamoeba infections of the eye and ocular adnexa; Marines HM et al.; In search of an easy and quick method for the diagnosis of fungal and Acanthamoeba infections of the eye, the authors have used calcofluor white (CFW), a fluorescent brightener with marked affinity for chitin and cellulose which are present in the cell walls of fungi and cysts of Acanthamoeba . Paraffin-embedded tissues containing mycotic organisms were stained with CFW and examined under a fluorescent microscope . Several fungi such as Candida sp, Aspergillus sp, Phycomycetes, Fusarium solani, Histoplasma capsulatum, Cryptococcus neoformans, Rhinosporidium seeberi, and others were studied . Trephine corneal biopsy specimens (2 mm) and methanol-fixed corneal scrapings containing Acanthamoeba sp were also examined . The walls of fungi and Acanthamoeba cysts stained bright greenish white in contrast to the reddish-orange background of the supporting tissues . The results demonstrate that the CFW method is a highly reliable and rapid technique for identification of mycotic organisms as well as cysts of Acanthamoeba . This method may also be applied in surgical pathology when performing frozen sections, as well as cytologic examination of corneal smears, vitrectomy specimens, and others.

Arch Inst Pasteur Tunis, 1986 Dec, 63(4), 477 - 80
{2 cases of mycotic infection caused by Cryptococcus neoformans}; Ben Jilani S et al.; The authors present two cases of Cryptococcus neoformans disease in two young persons . Its appears, in the first case, a diffuse ganglionnary and cutaneous lesion with an evolutive meningo-encephalic localization, and in the second case it appears only a meningitic lesion . These two observations are characterized by the apparition of the infection in a immunodepression patient and by an unfavorable evolution in spite of the treatment.

J Neurol Sci, 1986 Dec, 76(2-3), 187 - 98
Neuropathology of acquired immunodeficiency syndrome (AIDS) . Analysis of 22 Brazilian cases; Rosemberg S et al.; PIP: Involvement of the central nervous system is not uncommon in patients with acquired immunodeficiency syndrome (AIDS) . The neuropathologic aspects of 22 consecutive autopsies of Brazilian AIDS victims were investigated to gain more information on this manifestation . 13 (59%) of these cases exhibited neuropathologic changes, including infection by Toxoplasma (4 cases), Cryptococcus neoformans (3 cases), viral encephalitis (4 cases), primary lymphomas (2 cases), isolated cerebral infarct (1 case), and reactive gliosis (1 case) . In 2 cases, primary lymphoma and viral encephalitis were associated . 3 of the 4 cases of toxoplasmosis had macroscopical abscesses in the region of the internal capsule, basal ganglia, or thalamus . Axonal spheroids in the gracilis and cuneatus nuclei were present . All 3 cryptococcosis cases demonstrated a meningeal inflammatory process; in addition, multiple microcysts were found in the cortex of the cerebral hemispheres and in the basal ganglia in 2 of these cases . The 4 encephalitis cases showed multiple microglial nodules and occasional foci of perivascular lymphocytic cuffings, with dissemination of lesions throughout the grey structures of the central nervous system . All 22 patients autopsied in this series were male; 19 were homosexual . Previous studies of the incidence of neurologic complications in AIDS reported in the US and European literature have yielded rates between 23-73% .

J Thorac Cardiovasc Surg, 1986 Dec, 92(6), 977 - 80
The thoracic surgical spectrum of acquired immune deficiency syndrome; Miller JI; The acquired immune deficiency syndrome has presented a complex and, as yet, unsolvable spectrum of pulmonary disease characterized by bizarre infections, pneumothoraces, respiratory distress, and death . Thirty-eight patients underwent 49 surgical procedures during 42 months . Ages of the patients ranged from 24 to 56 years . Surgical procedures included tracheostomy, closure of air leaks, mediastinoscopy, lobectomy, open lung biopsy, and esophagogastrectomy . Hospital mortality was 10 of 38 (24%); the 1 year survival rate was 13 of 38 (34%) . Pulmonary infections included Pneumocystis carinii, cytomegalovirus, Microbacterium avium, toxoplasmosis, candidiasis, and Cryptococcus neoformans . Open lung biopsy and surgical closure of air leaks can be accomplished safely with low morbidity . Tracheostomy and ventilatory support should be avoided at present in the majority of patients with this syndrome, as the mortality has been 100% when that stage of the disease is reached.

Arq Neuropsiquiatr, 1986 Dec, 44(4), 351 - 8
{Cerebrospinal fluid signalization in chronic inflammatory diseases of the central nervous system}; Livramento JA et al.; Dynamics of cerebrospinal fluid (CSF) cyto-proteic dual obeys to different models when central nervous system (CNS) inflammatory diseases are considered . In order to evaluate these models data pertinent to multiple sclerosis (20 cases), neurosyphilis (20 cases), neurocysticercosis (20 cases), subacute sclerosing panencephalitis (20 cases), neuroschistosomiasis (18 cases) and neuro-cryptococcosis (20 cases) are compared in report to a control group: chronic vascular headache (50 cases) . CSF data on cytology and proteins were considered . Cytology was evaluated as to the total cell count (cumm); the cytomorphological profile (%) and as to lymphocytes subpopulations (B, T, T-active, T-sensitized, and T-avid for T-total and for T-active) . Proteins were evaluated as to the total content (mg/dl) and protein fractions (agar gel electrophoresis) . Antibodies determinations were studied for comparative purposes and diagnosis . Results were analyzed according to the groups considered and comparatively . Analyses support conclusions on cells and proteins dual interaction . This interaction is expressed by phenomena that obey similar parameters . These parameters permit to consider two models of chronic inflammatory signalization: the continuous model and the repetitive model . Neurosyphilis and subacute sclerosing panencephalitis obey the chronic continuous inflammatory model . Neurocysticercosis and multiple sclerosis obey the repetitive model.

J Med Vet Mycol, 1986 Dec, 24(6), 433 - 6
Systemic mycoses in the United States, 1980-1982; Reingold AL et al.; To evaluate temporal trends in the incidence of systemic mycoses resulting in hospitalization, we reviewed hospital discharge data from the Professional Activity Study of the Commission on Professional and Hospital Activities for 1980-1982 . In comparison with results from similar studies in 1970 and 1976, the incidences of the mycoses that are more likely to be opportunistic and/or hospital-acquired infections (candidiasis, aspergillosis, cryptococcosis) increased in 1980-1982 as did the incidences of sporotrichosis and actinomycosis . At the same time the incidences of most community-acquired mycoses (histoplasmosis, coccidioidomycosis, and blastomycosis) remained stable or declined . These results are consistent with the increasing number of immunocompromised patients with severe underlying illnesses, who are at risk of developing opportunistic mycoses.

J Infect Dis, 1986 Dec, 154(6), 944 - 51
Inhibition of complement by culture supernatants of Aspergillus fumigatus; Washburn RG et al.; Aspergillus fumigatus produced a water-soluble extracellular material that inhibited the opsonization of fungal cells by normal human serum . Blastospores of Cryptococcus neoformans and conidia from A . fumigatus or Aspergillus niger were used as fungal targets for ingestion by human monocytes . The opsonic inhibitor from A . fumigatus was found to decrease binding of complement component C3b to fungal surfaces by selectively interfering with activation of the alternative complement pathway . Inhibition of complement did not appear to result simply from proteolysis, as judged by the minimal degradation of casein and of purified C3 and C4 . The complement-inhibiting activity was partially labile to heating at 100 C and could be concentrated by using dialysis tubing with a 10,000-dalton exclusion limit . Aspergillus flavus, which is also a pathogen for humans, also produced this activity; A . niger did not . We speculate that this material may represent a pathogenesis factor for Aspergillus species.

J Immunol, 1986 Dec 1, 137(11), 3624 - 31
Natural cellular resistance of beige mice against Cryptococcus neoformans; Hidore MR et al.; Previous reports have demonstrated that natural killer (NK) cells are capable of inhibiting the growth of Cryptococcus neoformans in vitro, and recent studies indicate that adoptively transferred NK cell-enriched spleen cell populations enhance clearance of cryptococci from the tissues of cyclophosphamide-pretreated recipients . The primary objective of these studies was to confirm that NK cells participate in early clearance of C . neoformans in vivo . Secondarily, the anti-cryptococcal activities of polymorphonuclear leukocytes and macrophages were examined . Seven-week-old C57BL/6 bg/+ mice, which have normal levels of NK cell activity, were compared with their bg/bg littermates, which have impaired NK cell function . One and 3 days after injecting both groups of mice i.v . with 2 X 10(4) cryptococci, we assessed the NK cell activities in spleens, lungs, and livers and clearance of the organism from corresponding tissues as determined by the mean log10 numbers of cryptococcal colony-forming units (CFU) per organ . Three days postinfection, the mean numbers of cryptococcal CFU in lungs and spleens of bg/+ mice were significantly lower than in the corresponding organs of bg/bg mice . NK cell activities in spleens and lungs of bg/+ mice were significantly higher than were the NK cell activities in similar cell populations from bg/bg mice . In contrast, the mean numbers of cryptococcal CFU in livers of the two groups of animals were nearly equivalent, a situation not unexpected, since liver NK cell activities were extremely low and similar in both groups of animals . Although these data indicated a correlation between early clearance of cryptococci from tissues and levels of NK cell activities in the corresponding tissues, it was also possible that differences in phagocytic cell function between the bg/+ and bg/bg animals could account for the observed differences in clearance of cryptococci from the tissues . Therefore, phagocytic cells from the two groups of animals were compared with respect to their abilities to phagocytize and inhibit the growth of cryptococci and to their abilities to respond to chemotactic stimuli in vivo . Peritoneal PMNL from bg/+ and bg/bg mice were similar in their abilities to phagocytize and inhibit the growth of cryptococci, as well as in their chemotactic responses to viable cryptococci or sodium caseinate . In addition, there were no differences in splenic macrophage functions between the two groups of mice.(ABSTRACT TRUNCATED AT 400 WORDS)

Infect Immun, 1986 Dec, 54(3), 742 - 50
Binding of purified and radioiodinated capsular polysaccharides from Cryptococcus neoformans serotype A strains to capsule-free mutants; Small JM et al.; Strains 6, 15, 98, 110, and 145 of Cryptococcus neoformans serotype A vary in capsule size, animal virulence, and susceptibility to in vitro phagocytosis . The isolated capsular polysaccharides (CPSs) differ in monosaccharide composition ratios and molecular size, as determined by gel filtration . The purpose of this investigation was to characterize the binding of CPSs to capsule-free mutants of C . neoformans and to examine CPSs from these strains for differences in their ability to bind, to determine whether such differences might explain the variation in the pathobiology of these strains . CPSs were partially periodate oxidized, tyraminated, iodinated with 125I, and used in binding studies with two capsule-free mutants of C . neoformans, strain 602 and Cap59 . Binding was specific for yeast species and for polysaccharide and was saturable, which is consistent with a receptor-mediated mechanism of attachment . Binding occurred rapidly and was only slowly reversible . Binding was also independent of pH from pH 5.5 to 8, of cation concentrations, and of competition by sugars up to 1.0 M concentrations . Only a portion of CPS was capable of binding, and strains varied in the extent to which their CPS bound . CPS-15-IV (peak IV was the major polysaccharide peak on DEAE-cellulose chromatography of CPS from strain 15) had the highest proportion of binding (40%), followed by CPS from strains 98, 6, 145, 110, and 15-III (peak III was an earlier eluting fraction of CPS from strain 15) . The CPSs differed similarly in their ability to competitively inhibit binding . Treatment of CPS, but not yeast cells, with proteinase XIV abolished binding without altering the CPS gross structure . Treatment of yeast cells with proteases, heat, or formaldehyde did not alter binding, and both strain 602 and Cap59 bound CPS similarly . Binding to encapsulated yeast cells was minimal.

Infect Immun, 1986 Dec, 54(3), 735 - 41
Strain variation in composition and molecular size of the capsular polysaccharide of Cryptococcus neoformans serotype A; Small JM et al.; The capsule of Cryptococcus neoformans is an important virulence factor . In this investigation capsular polysaccharides (CPSs) were isolated by ethanol precipitation from culture filtrates of C . neoformans serotype A strains 6, 15, 98, 110, and 145 . Capsule sizes on India ink examination ranged from barely perceptible (strain 15) to greater than the diameter of the yeast cell (strain 6); the others were intermediate in size . On ion-exchange chromatography on DEAE-cellulose each CPS eluted at 0.2 M NaCl; CPS of strain 15 had two major peaks, designated III and IV . On gel-permeation chromatography CPSs of strains 6, 98, 110, and 145 eluted at the void volume of Sepharose CL-2B in the presence or 0.1 M EDTA, while the CPS of strain 15 eluted in two peaks . Sephacryl S-1000 resolved CPSs of all five strains in the following order, from largest to smallest molecular size: 145 greater than 110 greater than 98 greater than 6 much greater than 15 . All five CPSs contained mannose, xylose, and glucuronic acid, while the carboxyl-reduced CPS of strain 110 also contained a large percentage of an inositol-like compound . The CPS of strain 110 contained approximately 30% uronic acid by weight, while the others had 15 to 20% . The composition of peak IV from the CPS of strain 15 resembled those of the other strains; peak III of strain 15 contained a substantial amount of galactose . Each CPS contained less than 0.2% protein by weight . The significant differences in molecular size and sugar composition among CPSs of these strains of C . neoformans serotype A may partially explain strain differences in virulence and biological properties of the organism.

Acta Neurol Scand, 1986 Dec, 74(6), 467 - 74
Neurological complications and concomitants of AIDS; Helweg-Larsen S et al.; A survey of the literature of neurological manifestations associated with the acquired immune deficiency syndrome (AIDS) shows a broad disease spectrum affecting approximately one third of the patients in large hospital series . The complications include focal cerebral lesions caused by abscesses, lymphomas, leucoencephalopathy or infarcts as well as encephalitis, meningitis and myelitis . Most opportunistic infections of the central nervous system presumably are caused by toxoplasma gondii, cytomegalovirus and cryptococcus neoformans . One tenth of all patients have neurological disease as their initial symptom of AIDS . The diagnosis should always be considered in patients at risk and in males with an unusual neurological history or with a peculiar CT scan of the brain . Besides the opportunistic complications of AIDS, LAV/HTLV-III itself probably attacks the nervous system and gives rise to concomitant lesions of the long tracts of the spinal cord with ataxia, paresis and spasticity and to subacute encephalopathy and peripheral nerve abnormalities as well.

Science, 1986 Nov 21, 234(4779), 955 - 63
AIDS in Africa: an epidemiologic paradigm; Quinn TC et al.; Cases of the acquired immune deficiency syndrome (AIDS) have been reported in countries throughout the world . Initial surveillance studies in Central Africa suggest an annual incidence of AIDS of 550 to 1000 cases per million adults . The male to female ratio of cases is 1:1, with age- and sex-specific rates greater in females less than 30 years of age and greater in males over age 40 . Clinically, AIDS in Africans is often characterized by a diarrhea-wasting syndrome, opportunistic infections, such as tuberculosis, cryptococcosis, and cryptosporidiosis, or disseminated Kaposi's sarcoma . From 1 to 18% of healthy blood donors and pregnant women and as many as 27 to 88% of female prostitutes have antibodies to human immunodeficiency virus (HIV) . The present annual incidence of infection is approximately 0.75% among the general population of Central and East Africa . The disease is transmitted predominantly by heterosexual activity, parenteral exposure to blood transfusions and unsterilized needles, and perinatally from infected mothers to their newborns, and will continue to spread rapidly where economic and cultural factors favor these modes of transmission . Prevention and control of HIV infection through educational programs and blood bank screening should be an immediate public health priority for all African countries.

J Neurol, 1986 Nov, 233(6), 362 - 6
Cryptococcal meningoencephalitis: intrathecal immunological response; La Mantia L et al.; The intrathecal immune response is reported in a patient with cryptococcal meningoencephalitis . CSF IgM and IgG levels were significantly related to the favourable clinical evolution . IgM response was specifically directed against the pathological agent, while IgG were mostly non-specific . The data are discussed and compared with the other chronic infections of the central nervous system.

Mycopathologia, 1986 Nov, 96(2), 91 - 6
Evaluation of a fluorescent method (fluorescein diacetate and ethidium bromide solution) in the study of the viability Cryptococcus neoformans strains; Correa B et al.; The effectiveness of the fluorescent viability test (fluorescein diacetate-FDA and ethidium bromide-EB-solution) compared to the plaque counting test (Miles & Misra M & M) was performed on 10 samples of Cryptococcus neoformans cultivated in Sabouraud dextrose agar at 25 degrees C . The optimum incubation period of 50 minutes was determined . Growth curves of the fungal strains studied based on the mean cell number were drawn for both the FDA & EB and M & M methods . The statistical evaluation (Student's T test) of the average sum of the viable cell counts showed that the FDA-EB method is more sensitive than the M & M test for the studied species . The growth curves of the samples usually followed a homogeneous pattern comparable to other non-dimorphic fungi.

J Clin Microbiol, 1986 Nov, 24(5), 860 - 2
Disseminated cryptococcosis presenting as cellulitis with necrotizing vasculitis; Shrader SK et al.; Patients with disseminated cryptococcosis infrequently present with cutaneous involvement . Skin lesions, when present, are usually multiple and polymorphous in appearance . Cellulitis caused by Cryptococcus neoformans is rare, and necrotizing vasculitis associated with cryptococcal vascular invasion has not to our knowledge been reported . We report here a case of disseminated cryptococcosis in a renal transplant recipient who had cellulitis and necrotizing vasculitis and in whom a diagnostic skin biopsy allowed for early therapy with cure and salvage of the renal allograft.

Vardfacket, 1986 Oct 23, 10(19), 28 - 30
{AIDS in Africa}; Neander L et al.; PIP: The main aspects of the acquired immunodeficiency syndrome (AIDS) epidemic in Africa as of mid-1986 are discussed . In certain parts of Africa the disease appears to be widespread and fairly evenly divided between the sexes . Most of the AIDS patients have traveled a great deal and been very active sexually, even while traveling . Prostitutes in such large cities as Nairobi are heavily infected with HIV . Recognized routes of infection are: sexual transmission, blood transfusion, contaminated injection equipment, and mother to child . The pathology of AIDS involves the death of the helper cell type of T-lymphocytes, which increases the patient's susceptibility to infections and tumors . There is some evidence that the HIV epidemic originated in central Africa, possibly as a mutant of the green monkey fever virus, and gradually spread to Europe and the USA . Clinically, AIDS should be suspected with such symptoms as persistent unexplained fever, chronic diarrhea, lymphadenopathy, severe wasting, and itching skin lesions, primarily on the extremities . Definitive symptoms include such opportunistic infections as candida esophagii, cryptococcus, severe varieties of herpes simplex, pneumocystis carinii pneumonii, disseminated strongyloids, cerebral toxoplasmosis and a typical mycobacteria . Serological diagnostic tests include enzyme linked immunosorbent assay (ELISA) and Western blot, both of which require advanced equipment . No treatment for AIDS is known; management should concentrate on preventing opportunistic infection .

Arch Dermatol, 1986 Oct, 122(10), 1186 - 90
Disseminated Nocardia brasiliensis infection following cryptococcal disease; Schreiner DT et al.; Nocardiosis is an increasing clinical problem, especially in immunocompromised patients . The offending species is almost always Nocardia asteroides . Cryptococcosis is also an increasing problem in the immunosuppressed . We describe a patient with probable disseminated cryptococcosis followed by disseminated Nocardia brasiliensis infection . Only eight patients with disseminated N brasiliensis infection have been described, to our knowledge, in the United States.

Urology, 1986 Oct, 28(4), 318 - 9
Prostatic cryptococcosis in acquired immune deficiency syndrome; Lief M et al.; A rare care is presented of recurrent dysuria and urinary obstruction due to cryptococcal prostatitis in a thirty-six-year-old male with acquired immune deficiency syndrome . Although there are a handful of reports in the world literature of patients with cryptococcal prostatitis, this appears to be the first case reported related to acquired immune deficiency syndrome.

Mycopathologia, 1986 Oct, 96(1), 33 - 40
In vivo and in vitro studies with an atypical, rhinotropic isolate of Cryptococcus neoformans; Dixon DM et al.; An atypical isolate of Cryptococcus neoformans was investigated because of its consistent and reproducible production of gross nasal pathology following i.v . injection in Swiss albino mice . Dose response to graded concentrations ranging from 1 X 10(2)-1 X 10(7) cells/mouse yielded an LD50 of 1.4 X 10(3) cells/mouse for the atypical rhinotropic strain H140 which was significantly less virulent (p less than 0.01) than our reference strain of Cryptococcus neoformans . There was no significant difference in mortality following the injection of in vitro vs . in vivo passed inoculum . As early as two weeks after inoculation, this strain produced gross nasal enlargement to approximately 2-3 X normal dimensions with granulomatous and ulcerated lesions . The LD60 resulted in the greatest percentage of nasal involvement (85%) . C . neoformans was demonstrated by culture and histopathology in the noses, brains, lungs, livers and kidneys . A temperature selection was indicated by findings of a lower temperature minimum for subcultures isolated from the noses relative to those isolated from the brain, and by the fact that the most densely populated organs following intraperitoneal injection were the testes . This route of inoculation resulted in cutaneous nasal involvement in a manner analogous to that following i.v . injection . The atypical isolate was unable to assimilate trehalose or raffinose but otherwise was entirely consistent with identification as C . neoformans and produced characteristic CNS and general organ system disease in addition to the rhinotropic cutaneous manifestations . The model characterized here in normal mice may be of value in studies of fungal dermotropism.

Mycopathologia, 1986 Oct, 96(1), 25 - 8
Primary cutaneous cryptococcosis; Moreno Castillo JL et al.; A 7-year-old boy, without apparent underlying disease, but with a non-specific failure in his cellular immunity, developed a cutaneous lesion on the left retroauricular area with spontaneous healing . Mycologic study revealed Cryptococcus neoformans, a capsule deficient strain, as the etiologic agent.

Radiology, 1986 Oct, 161(1), 87 - 93
Pulmonary manifestations of AIDS: review of 106 episodes; Suster B et al.; We reviewed the clinical records and chest radiographs of all patients admitted to our institution between 1982 and 1984 who had pulmonary disease and who were later proved to have acquired immunodeficiency syndrome (AIDS) (95 patients) . Diffuse parenchymal lung disease was the most common finding . These infiltrates were usually interstitial and caused by Pneumocystis carinii pneumonia or P . carinii combined with cytomegalovirus infection . Focal, multilobar, interstitial infiltrates were also often seen and usually caused by P . carinii or P . carinii and cytomegalovirus infections . Rarely, well-defined, multiple, interstitial nodules less than 10 mm in diameter were the only or predominant characteristic and were seen only in association with Mycobacterium tuberculosis or Cryptococcus neoformans infections or Kaposi sarcoma . Hilar or mediastinal adenopathy occurred in 17 of the 21 patients with M . tuberculosis or C . neoformans infections . In contrast, only 4% of patients with P . carinii infections presented with these findings . We also found that hilar or mediastinal adenopathy was not significantly associated with peripheral adenopathy . Lung cavitation, pleural effusion, or a normal chest radiograph was uncommon.

Mikrobiologiia, 1986 Sep-Oct, 55(5), 851 - 4
{Characteristics of free water distribution in the cytoplasm of cryotolerant cells of Cryptococcus laurentii}; Ratner EN et al.; The resistance to freezing-thawing was studied with Cryptococcus laurentii cultivated at a near-zero plus temperatures in a minimal or a rich medium . At the transition into the stationary phase, the resistance of the cells to freezing increased 20 times in the culture grown in the minimal medium and 8 times in the culture grown in the rich medium . Free water localization in the cell cytoplasm was determined by electron microscopy . In yeast cells with the maximal cryotolerance, free water was found mainly between glycogen granules . The authors discuss the role of glycogen as of a possible factor making the cells resistant to low temperatures.

Can J Microbiol, 1986 Sep, 32(9), 756 - 8
Ascorbic acid specific utilization by some yeasts; Costamagna L et al.; One hundred and eighty strains of yeasts belonging to 17 genus and 53 species were screened for their ability to grow on ascorbic acid and iso-ascorbic acid as the sole carbon source . Most of the tested strains (157) were unable to grow on either compound . Strains of seven species of the genus Cryptococcus, of two Candida species, of Filobasidiella neoformans, Trichosporon cutaneum, Lipomyces starkeyi, Hansenula capsulata, and one strain of Aureobasidium pullulans were able to grow on ascorbic as well as on iso-ascorbic acid . Conversely, four strains of Aureobasidium pullulans, Candida blankii, and Cryptococcus dimennae could use only ascorbic acid for growth.

Mycopathologia, 1986 Sep, 95(3), 183 - 7
Susceptibility of clinical isolates of yeasts to anti-fungal agents; Hussain Qadri SM et al.; The antimicrobial activity of amphotericin B, 5-fluorocytosine, nystatin, clotrimazole and miconazole were compared in vitro against 244 strains of yeasts that had been isolated from clinical specimens . The yeasts used in this study included 20 species of Candida, Cryptococcus, Saccharomyces Geotrichum, Rhodotorula, Torulopsis and Trichosporon . The majority of the strains (78%) had an MIC of less than or equal to 0.5 microgram/ml for amphotericin B, 81% an MIC of less than or equal to 1 microgram/ml for 5-fluorocytosine, 99% less than or equal to 8 micrograms/ml for nystatin, 91%, less than or equal to 8.0 micrograms/ml for clotrimazole and 98% had an MIC of less than or equal to 4.0 for miconazole . Of the anti-fungal agents tested, 5-fluorocytosine and nystatin were found to have the greatest antifungal activity.

Clin Exp Immunol, 1986 Sep, 65(3), 639 - 46
Tolerance to cryptococcal polysaccharide in cured cryptococcosis patients: failure of antibody secretion in vitro; Henderson DK et al.; Ten patients cured of cryptococcosis and 14 normal volunteers were immunized with subcutaneous injections of cryptococcal polysaccharide (CPS) . Peripheral mononuclear cells cultured from the volunteers 7 days post-immunization secreted significant amounts of IgM, IgA and IgG antibody to CPS in vitro . In cell cultures obtained 7 days after immunization of patients, nine of 10 had neither IgM nor IgG antibody response to CPS, and eight lacked anti-CPS IgA . Depletion of T lymphocytes from patients' cell cultures did not promote specific antibody secretion to CPS by B cells . The intense, prolonged antigenaemia with CPS that accompanies cryptococcosis may be responsible for the failure of cured patients to have circulating anti-CPS-secreting cells after immunization.

Yeast, 1986 Sep, 2(3), 193 - 204
Orthogonal-field-alternation gel electrophoresis banding patterns of DNA from yeasts; de Jonge P et al.; Chromosomal DNAs from various yeast species were separated by orthogonal-field-alternation gel electrophoresis (OFAGE) . To this end we developed a spheroplasting and lysis method to obtain intact DNA from both ascomycetous and basidiomycetous yeasts . The OFAGE banding patterns of 22 ascomycetous and four basidiomycetous yeast strains were compared . The strains represented species from the genera: Brettanomyces, Candida, Cryptococcus, Filobasidiella, Geotrichum, Hansenula, Kluyveromyces, Pachysolen, Pichia, Rhodosporidium, Rhodotorula, Saccharomyces, Saccharomycodes, Saccharomycopsis, Schizosaccharomyces and Zygosaccharomyces . Variations occurred in the number of bands and their positions in the gel, not only among strains of different genera but also among species from the same genus and even between varieties of the same species . The ascomycetous yeasts, with the exception of Saccharomyces cerevisiae, only showed one to five bands of DNA larger than 1000 kilobase pairs (kb) in general none smaller . The patterns of the four basidiomycetous yeasts revealed also a few large DNA bands but in addition one to six bands ranging in size from 500 to 1000 kb, with the exception of a single smaller chromosome in Rhodotorula mucilaginosa . From the OFAGE banding patterns of strains studied here it appears that in Sacch . cerevisiae the partitioning of DNA over chromosomes is unique . But rather than the large number of chromosomes, the presence of four chromosomes with less than 500 kb of DNA is characteristic for Sacch . cerevisiae.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1986 Sep, 262(3), 417 - 24
Modulation of Bhanja virus infection in mice; Hubalek Z; Randombred (ICR) and inbred (C57B1/6) 4-wk-old SPF male mice were infected extraneurally with Bhanja virus (Bunyaviridae) and subjected to various treatments . Immunosuppression with cyclophosphamide (CPA) affected the course of the infection when a higher dose (10(6) suckling mouse intracerebral LD50) of the virus and 2 or 3 injections of CPA (150 mg/kg each) were given: then a part of the animals died due to viral encephalitis, whereas all the CPA-untreated infected mice survived . A dual peripheral infection with Bhanja and Lipovnik (Reoviridae) viruses did not cause any symptomatic response, and the host's humoral antibody was slightly stimulated . When Bhanja virus was given prior to, or simultaneously with, tick-borne encephalitis virus (Flaviviridae), a moderate decrease of the mortality (due to tick-borne encephalitis) occurred . A mixed peripheral infection of mouse with Bhanja virus and Cryptococcus neoformans, did not result in a fatal virus encephalitis of the host, nor was cryptococcosis affected substantially . However, formalin-killed cells of the fungus ("cryptococcin") administered before the extraneural inoculation of Bhanja virus caused an 8-fold increase of antibodies neutralizing the virus; a mild therapeutic or protective effect of cryptococcin on encephalitis after an intracerebral application of Bhanja virus was also observed.

Diagn Cytopathol, 1986 Sep, 2(3), 181 - 6
Pulmonary cytology of the acquired immune deficiency syndrome: an analysis of 36 cases; Duggan MA et al.; The infectious pathogens and associated cellular reactions in 75 pulmonary cytological specimens obtained largely by fiberoptic bronchoscopy from 36 patients with the acquired immune deficiency syndrome are described and correlated with the biopsy specimens . An opportunistic pathogen was diagnosed in 33% of cytological preparations . Pneumocystis carinii was encountered most frequently; Cryptococcus neoformans and cytomegalovirus were also seen . The polymorphonuclear neutrophil was the predominant inflammatory cell . Cells of secondary import were bronchial cells and type II pneumocytes with atypia and hyperplasia . Bronchoalveolar lavage had the highest yield, positive predictive value, and sensitivity for all pathogens and for P . carinii . An opportunistic pathogen was diagnosed in 69% of patients utilizing histological material and in 33% using cytological samples; the rate of diagnosis increased to 72% when the samples were combined.

Am J Pathol, 1986 Sep, 124(3), 537 - 58
The neuropathology of AIDS . UCLA experience and review; Anders KH et al.; The central nervous system (CNS) has been examined at autopsy in 89 patients who died of the acquired immune deficiency syndrome (AIDS), including 14 patients who died primarily of neurologic complications of the disease . A total of 66 brains (74%) showed significant pathologic abnormalities, with opportunistic infections including cytomegalovirus (14) and cryptococcal (11) infections, progressive multifocal leukoencephalopathy (6), toxoplasmosis (6), and histoplasma microabscesses (1) . Incidental Mycobacterium avium-intracellulare infection was found in 4 cases . Simultaneous CNS infection by more than one microorganism was encountered in 5 patients . Subacute (microglial nodule) encephalitis-related to cytomegalovirus infection or possibly brain infection by the causative agent of AIDS was present in 56 cases . Primary CNS lymphoma was noted in 3 patients . Secondary CNS deposits of lymphoma were found in 1 patient, and another patient had lymphomatoid granulomatosis . Vascular complications were not infrequently seen, and included infarcts secondary to vessel occlusion and disseminated intravascular coagulation in 4 patients and intracranial hemorrhage of variable severity in 13 . White matter changes included vacuolar myelopathy (3 cases), central pontine myelinolysis (1 case), and foci of calcified, necrotizing leukoencephalopathy in pontocerebellar fibers of the basis pontis (2 cases) . These findings highlight the variety of CNS complications in AIDS, some of which are not associated with clinical manifestations . Nevertheless, characterization of all lesions may be important in understanding the neurologic sequelae of AIDS.

Eur J Clin Microbiol, 1986 Aug, 5(4), 379 - 88
New developments in the diagnosis of opportunistic fungal infection; Hopwood V et al.; This review considers recent developments in the diagnosis of aspergillosis, candidosis and cryptococcosis and discusses the prospects for routine application of a number of novel methods . The introduction of lysis-centrifugation and radiometric methods for blood culture has improved the diagnosis of deep candidosis, but the value of these methods for the diagnosis of aspergillosis has not yet been determined . Recent developments in serological diagnosis have included the evaluation of newly discovered antigens of Candida albicans in an attempt to distinguish colonization from significant infection . Antigen detection, an established method for the diagnosis of cryptococcosis, has also been evaluated and appears promising for the diagnosis of aspergillosis and candidosis . Another promising approach has been the use of gas-liquid chromatography to detect fungal metabolites in serum and other host fluids.

J Clin Microbiol, 1986 Aug, 24(2), 269 - 71
Influence of culture medium on susceptibility testing with BAY n 7133 and ketoconazole; Hoeprich PD et al.; The effect of four culture media (two complex and undefined {Sabouraud glucose and Kimmig} and two synthetic and defined {synthetic amino acid medium, fungal, and modified yeast nitrogen base}) on the activity in vitro of two newer azole compounds (BAY n 7133 and ketoconazole) was assessed with five strains each of Candida albicans, Candida parapsilosis, and Cryptococcus neoformans . Also, the nutritional adequacy of the four media was evaluated with the same 15 strains of yeastlike fungi . While the MICs of BAY n 7133 were higher in the complex media, the activity of ketoconazole was little affected . The Candida spp . grew least well and the C . neoformans grew best in yeast nitrogen base.

J Am Vet Med Assoc, 1986 Aug 1, 189(3), 302 - 4
Cryptococcosis involving the eye and central nervous system of a dog; Jergens AE et al.; Cryptococcus neoformans meningoencephalitis was diagnosed as the cause of stupor and generalized seizures in a 2-year-old Cocker Spaniel . Unilateral granulomatous chorioretinitis was observed ophthalmoscopically, and isolation of C neoformans from CSF confirmed the antemortem diagnosis . The dog was euthanatized and necropsied . Multifocal lesions were seen throughout the lungs, nasal turbinates, cerebral cortex, and the optic nerve of each eye . Microscopically, the multifocal lesions were granulomas consisting of lymphocytes, macrophages, plasma cells, and cryptococcal organisms . Infection may have originated in the nasal passages and extended directly through the ethmoid plate into the meninges of the CNS and optic nerves . Although the prognosis is poor in dogs with CNS involvement, various chemotherapeutic agents are available for use by clinicians.

Am J Clin Pathol, 1986 Aug, 86(2), 204 - 8
Differentiation of Cryptococcus neoformans serotypes by isoenzyme electrophoresis; Safrin RE et al.; Cryptococcus neoformans has been divided into four serotypes by specific agglutination in immune rabbit sera . Based on mating characteristics of the perfect state and epidemiologic and biochemical differences, the serotypes have been divided into two major pairs . In an attempt to characterize the serotypes further, the authors studied 22 strains of C . neoformans by the technic of horizontal starch-gel isoenzyme electrophoresis . The glucose-phosphate isomerase and phosphoglucomutase of serotypes A, C, D, and a subset of the serotype B strains migrated to distinguishable locations in this system . The activities of the remainder of the serotype B strains co-migrated with the serotype C strains . Thus, this technic distinguishes all the serotypes of C . neoformans except for a subset of serotype B and should be a useful adjunct for further elucidation of the epidemiologic and biochemical differences among serotypes.

J Antimicrob Chemother, 1986 Aug, 18(2), 261 - 70
Treatment of cryptococcal meningitis in mice with fluconazole; Palou de Fernandez E et al.; Fluconazole is a recently developed triazole with activity in vitro against Cryptococcus neoformans, water solubility, and excellent oral absorption . We compared fluconazole in murine cryptococcosis with ketoconazole and amphotericin B . Fluconazole was highly effective in suppressing cryptococcosis in mice challenged by the intravenous and intranasal routes, and was comparable with the other two drugs in its protective capacity . However, fluconazole was superior to ketoconazole and comparable with amphotericin B after intracerebral challenge . Fluconazole may warrant clinical evaluation in cryptococcosis.

J Immunol, 1986 Jul 15, 137(2), 693 - 701
Macrophage-mediated fungistasis: requirement for a macromolecular component in serum; Granger DL et al.; Peritoneal macrophages from Mycobacterium bovis- or Toxoplasma gondii-infected mice cultured in vitro in Dulbecco's medium containing 10% fetal bovine serum (FBS) and endotoxin stopped replication of Cryptococcus neoformans for 30 hr, whereas yeast cells cultured alone reproduced with a 3.0-hr doubling time . Without at least 5% FBS, macrophage fungistasis was poor . FBS without macrophages enhanced the growth rate of cryptococci . Macrophages preincubated in vitro for 24 hr without serum became fungistatic when challenged with cryptococci in medium with FBS but were not fungistatic without FBS . Macrophages preincubated in medium with FBS were never subsequently fungistatic . Dialyzed, heated (56 degrees C, 30 min), or delipidated FBS supported macrophage fungistasis, whereas FBS heated at 70 degrees C for 30 min did not . FBS contained no measurable opsonic activity for C . neoformans . Inclusion of endotoxin and/or murine IFN-gamma over wide concentration ranges did not substitute for FBS . Ultrafiltration estimation of FBS activity localized to 50 to 150 Kd . By gel filtration chromatography, FBS activity ran in the 25 to 100 Kd range . Dye-ligand affinity chromatography on Cibacron blue agarose gel dissociated the FBS activity from the albumin and lipoprotein fractions . Anion-exchange chromatography on DEAE-Sephacel revealed activity in the first fraction eluting at low ionic strength, pointing to a protein(s) with an isoelectric point toward neutral . Activated macrophages can prevent microbial replication within host tissues; the local environment is critical for fulfillment of this important physiologic function . These results point to a macromolecular factor(s) present in serum that is essential for full fungistatic capability of activated macrophages.

Dtsch Med Wochenschr, 1986 Jul 4, 111(27), 1061 - 5
{Disseminated cryptococcosis in 2 AIDS patients . A contribution to cryptococcosis diagnosis in AIDS}; Staib F et al.; In two AIDS patients (homosexual men) microscopical demonstration of Cryptococcus neoformans in samples obtained by puncture of the liver (n = 1) and additionally of the spleen (n = 1) led to the diagnosis of systemic cryptococcosis . Using the India ink method capsulated Cryptococcus neoformans cells could also be detected in cerebrospinal fluid (CSF) and urine . Concomitant culture of the fungus from tracheal secretion, CSF, urine and faeces confirmed the diagnosis of a disseminated infection; the identification and germ count of C . neoformans was achieved by means of the differential-selective medium Guizotia-abyssinica-creatinine agar . The C . neoformans antigen titres in serum and CSF corresponded to the stage of the mycosis as detected by microscopy and culture . After a six-week course of treatment with amphotericin B and flucytosine (Ancotil), the fungus could no longer be isolated from the materials examined in one patient . Mycological monitoring aiming at the detection of C . neoformans in the tracheal secretions by means of the mentioned differential-selective medium is therefore recommended as a prophylactic measure in AIDS patients and persons at risk.

Med Trop (Mars), 1986 Jul-Sep, 46(3), 275 - 80
{Therapy of deep mycoses}; Aubry P et al.; In 1985, available drugs to cure deep mycosis are in fact limited to amphotericin B (Fungizone), 5-fluorocytosine (Ancotil) and ketoconazole (Nizoral) . Potassium iodide is not much utilized . In diffuse aspergillosis and meningitic cryptococcosis, Fungizone by I.V . injection remains the high-grade antifungal drug--Ancotil is not actually used anymore in mono-therapy, but associated either with Fungizone in cryptococcosis and diffuse aspergillosis, or with Nizoral in systemic candidosis--Nizoral, which does not diffuse in C.S.F . and has a limited efficiency in immunosuppressive patients, is recommended in systemic candidosis and tropical deep mycosis, particularly histoplasmosis, blastomycosis, entomophtoromycosis, as well as in candidosis and diffuse aspergillosis prophylaxis in people at high risk . New antimycosis drugs are under studies: itraconazole efficient against aspergillus and fluconazole, which diffuses in C.S.F . and has a long time action.

Med Trop (Mars), 1986 Jul-Sep, 46(3), 263 - 7
{Deep mycoses rarely described}; Charles D; Beside deep mycoses very well known: histoplasmosis, candidosis, cryptococcosis, there are other mycoses less frequently described . Some of them are endemic in some countries: South American blastomycosis in Brazil, coccidioidomycosis in California; some others are cosmopolitan and may affect everyone: sporotrichosis, or may affect only immunodeficient persons: mucormycosis . They do not spare Africa, we may encounter basidiobolomycosis, rhinophycomycosis, dermatophytosis, sporotrichosis and, more recently reported, rhinosporidiosis . Important therapeutic progresses have been accomplished with amphotericin B and with antifungus imidazole compounds (miconazole and ketoconazole) . Surgical intervention is sometime recommended in chromomycosis and rhinosporidiosis.

Med Trop (Mars), 1986 Jul-Sep, 46(3), 257 - 60
{Mycoses in AIDS in the Central African Republic}; Lesbordes JL et al.; Among the 155 cases of A.I.D.S . observed by the authors in Bangui (C.A.R.) from April 1985 to February 1986, 49 patients (31.6%) were carriers of mycosis . 42 candidosis, 5 cryptococcosis, 2 aspergillosis were found; the authors describe the clinical aspects, the localizations and the methods of diagnosis.

Med Trop (Mars), 1986 Jul-Sep, 46(3), 249 - 56
{Cryptococcosis in Burundi in 1985 . Report of 30 cases}; Laroche R et al.; Over a period of 23 months, 30 cases of cryptococcosis have been studied in Bujumbura (Burundi) . Through them, epidemiological and clinical aspects have been underlined, and attempts have been made to establish links between cryptococcosis and A.I.D.S., which is significantly frequent in Central Africa . Cryptococcosis strikes young adults (40% between 30 and 35 years of age) . Its high frequency in Bujumbura among patients infested by A.I.D.S., suggest some thoughts . A.I.D.S . in Central Africa, and particularly in Burundi, presents some peculiarities linked to surrounding and possibilities of diagnosis: opportunistic diseases are of different frequency in temperate or tropical climates: pneumocystosis are more frequent in U.S.A . but cryptococcosis and candidosis are more frequent in Africa because their diagnosis is easier . lack of classical risk factors in African populations is known, but other risk factors have to be taken into consideration: tuberculosis, intestinal parasitosis, chronic virus B hepatitis, protein-caloric deficiency.

Stroke, 1986 Jul-Aug, 17(4), 753 - 4
Sudden hemiparesis as the presenting sign in cryptococcal meningoencephalitis; Saul RF et al.; A previously healthy young man presented with an acute stroke syndrome and was found to have cryptococcal organisms in the CSF . Though an initial CSF examination for an infectious etiology was negative, a second lumbar puncture was performed because of hypoglycorrhachia, which established the diagnosis . An uneventful recovery followed the administration of Amphotericin B and 5-Flucytosine . A literature search revealed only one previously reported case of cryptococcal meningoencephalitis presenting as a stroke . The need for performing a CSF examination on young patients presenting with a cerebrovascular event, and the aggressive investigation of unexplained hypoglycorrhachia are emphasized.

Am J Med, 1986 Jul, 81(1), 24 - 8
Intraventricular therapy of cryptococcal meningitis via a subcutaneous reservoir; Polsky B et al.; Intraventricular administration of amphotericin B for meningitis due to Cryptococcus neoformans is usually reserved for selected, seriously ill patients with recurrent disease . Between September 1973 and November 1983, 10 of 23 patients treated for cryptococcal meningitis at Memorial Sloan-Kettering Cancer Center received intraventricular amphotericin B through subcutaneous reservoirs, in addition to systemic therapy . The value of intraventricular amphotericin B was assessed in the 13 patients treated for first episodes of meningitis with systemic amphotericin B and flucytosine . Death during therapy occurred in one of six patients with intraventricular and systemic therapy compared with six of seven patients with systemic therapy alone (p = 0.025) . The cerebrospinal fluid was sterilized in six of six patients given systemic and intraventricular therapy compared with three of seven given systemic therapy alone (p = 0.049), and the cerebrospinal fluid cryptococcal antigen titer declined in six of six patients given systemic and intraventricular therapy compared with two of seven given systemic therapy alone (p = 0.016) . In the 10 patients who received intraventricular therapy, there were no complications related to reservoir insertion; however, complications related to reservoir use requiring replacement or revision occurred in two patients, and bacterial infection occurred in one but was treated successfully without removal of the reservoir . Although these data are retrospective, they suggest that early therapy with intraventricular amphotericin B in combination with systemic therapy may be beneficial and relatively safe in patients with cryptococcal meningitis and a poor prognosis.

Am J Clin Pathol, 1986 Jul, 86(1), 105 - 7
Bacteremia and fungemia in patients with acquired immune deficiency syndrome; Eng RH et al.; Patients with acquired immune deficiency syndrome (AIDS) are known to have identifiable host defense deficiencies, especially deficiencies in cell-mediated immunity . They are at increased risk for developing infections of the bloodstream caused by Cryptococcus neoformans and Salmonella species . However, bacteremias caused by other enteric gram-negative rods and Pseudomonas aeruginosa are found less frequently in patients with AIDS than in patients without AIDS (P less than 0.001 and P less than 0.01, respectively) . The findings of specific organisms in blood is consistent with the known types of host defense deficiencies in these patients.

J Allergy Clin Immunol, 1986 Jul, 78(1 Pt 1), 102 - 8
Microbiologic analyses of nasal polyp tissue; Dunnette SL et al.; Nasal polyps from 40 patients were cultured within 2 1/2 hours after surgical removal to determine whether microorganisms were present . The first 20 polyps were cultured for aerobic and anaerobic bacteria, viruses, fungi, mycoplasmas, and mycobacteria . Of these 20 polyps, eight were sterile by all tests, one grew Cryptococcus albidus, one grew Sporobolomyces, one had large numbers of Peptostreptococcus micros and Propionibacterium acnes, greater than 10(6) colony-forming units per gram (cfu/gm), and nine had aerobic bacteria including 10 different species at levels less than 10(5) cfu/gm . The second 20 polyps were cultured for aerobic bacteria only; 11 polyps were positive . Overall, 14 of 26 polyps from patients with asthma and two of 14 polyps from patients without asthma were positive for aerobic bacteria at levels greater than 10(3) cfu/gm (p less than 0.05) . Multiple aerobic bacterial species tended to occur in polyps from patients with asthma (11 of 26) more frequently than in those from patients without asthma (one of 14) (p less than 0.01) . There was a highly significant positive correlation between tissue neutrophilia and bacterial count (r = +0.9; p less than 0.001) . The results indicate that patients with asthma have a significantly higher number and a tendency to a greater variety of aerobic bacteria in nasal polyp tissue than patients without asthma and that the number of infiltrating neutrophils is directly related to the number of bacteria.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1986 Jul, 261(4), 481 - 6
The susceptibility of Cryptococcus neoformans to an antimycotic agent (G2) from alfalfa; Polacheck I et al.; Compound G2, 2-beta-hydroxy-3-beta-O-(beta-D-glucopyranosyl)-delta 12-oleanene-23,28-dionic acid, isolated from alfalfa roots, demonstrated considerable activity against Cryptococcus neoformans (MIC value of 2 micrograms/ml) . Compound G2 exhibited rapid killing of this fungus (MFC value of 4 micrograms/ml) suggesting that it might be a useful active agent in the treatment of cryptococcosis.

Am J Med, 1986 Jul, 81(1), 19 - 23
Cryptococcal infections in patients with acquired immune deficiency syndrome; Eng RH et al.; Cryptococcus neoformans is a major pathogen in patients with acquired immune deficiency syndrome and was found to infect 13.3 percent of such patients seen at two medical centers . Serum cryptococcal antigen levels were as high as 1:2,000,000 and, despite therapy, often remained elevated . Antigen titers in the cerebrospinal fluid generally declined at an expected rate in the survivors . The significance of high antigen titers in the blood after a prolonged course of therapy with amphotericin B and 5-flucytosine is unknown.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1986 Jul, 261(4), 471 - 80
The biochemical basis for the distinction between the two Cryptococcus neoformans varieties with CGB medium; Min KH et al.; The biochemical basis for the reaction to canavanine-glycine-bromthymol blue (CGB) agar by Cryptococcus neoformans var . gattii and C . neoformans var . neoformans was investigated . All of the var . gattii isolates tested were found to utilize glycine as the sole source of carbon and nitrogen and were resistant to L-canavanine . Only 11% of the serotype D isolates of var . neoformans utilized glycine as the sole source of carbon and nitrogen, but these were all sensitive to canavanine . Nineteen percent of the serotype A isolates of var . neoformans were able to assimilate glycine, and 81% of the glycine users were resistant to canavanine . However, these canavanine-resistant, glycine-assimilating, var . neoformans isolates failed to grow when they were cultured on a medium containing glycine and canavanine . Unlike the var . neoformans isolates, all of the var . gattii isolates tested grew on a medium that contained both of these compounds . Glycine-utilizing isolates exhibited good uptake of the amino acid, and a glycine-cleaving enzyme was discernable in the isolate . The isolates that fail to utilize glycine accumulated the amino acid at a rate which was barely 15% of that seen in the glycine users, and no glycine-cleaving enzyme was apparent within the 48-hr incubation period . When a cell-free extract (which had been derived from a glycine-utilizing isolate), was incubated with 14C-labeled glycine, ammonia, radiolabeled CO2, and serine were produced . The glycine decarboxylase activity of the cell-free extract was found to be enhanced by the addition of dithiothreitol, tetrahydrofolate, pyridoxal phosphate, and nicotinamide adenine dinucleotide (NAD) . The ammonia released during glycine cleavage seems to be responsible for the positive reaction on CGB medium.

Chest, 1986 Jul, 90(1), 18 - 22
Bronchoalveolar lavage as the exclusive diagnostic modality for Pneumocystis carinii pneumonia . A prospective study among patients with acquired immunodeficiency syndrome; Golden JA et al.; Pneumocystis carinii pneumonia (PCP) is the most common life-threatening opportunistic infection among patients with the acquired immunodeficiency syndrome (AIDS) . Because retrospective studies suggested that bronchoalveolar lavage (BAL) compared favorably to lung biopsy in the diagnosis of PCP, we prospectively evaluated the utility of BAL in 40 consecutive patients with AIDS or risk of AIDS who presented with respiratory complaints . The BAL revealed P carinii in 36 of 42 episodes of pneumonia (86 percent) among 40 patients . Clinical follow-up of the six patients whose BAL was negative for PCP suggested only one possible false negative BAL for PCP . Therefore, BAL detected PCP in 36 of 37 patients for a sensitivity of 97 percent . BAL detected cytomegalovirus in 15 of 38 patients, as well as Mycobacterium avium-intracellulare and Cryptococcus (each in one patient) . By virtue of accuracy and lack of morbidity demonstrated in our study, BAL should supplant lung biopsy techniques in the evaluation of AIDS patients with pulmonary symptoms.

Arch Pathol Lab Med, 1986 Jun, 110(6), 502 - 7
The pathology of pulmonary cryptococcal infections in the acquired immunodeficiency syndrome; Gal AA et al.; Specimens from premortem pulmonary cytology, transbronchial biopsy, and autopsy were studied in 11 patients with acquired immunodeficiency syndrome who developed pulmonary cryptococcal disease . Nine of 11 patients had culture-proved cryptococcal meningitis . Extremely low T-cell helper/suppressor ratios (mean, 0.12) were observed in seven of 11 patients . In six of eight patients, transbronchial biopsy specimens showed a characteristic interstitial pattern with yeasts in the alveolar septae, minimal cellular inflammation, and no well-formed granulomas . On cytologic examination, organisms were present in seven (100%) of seven cell blocks and five (83%) of six smears prepared from the bronchoalveolar lavage, and in five (63%) of eight bronchial brushings . Small, poorly encapsulated yeast forms were sometimes present, requiring mucicarmine and acid mucopolysaccharide stains for confirmation of the diagnosis of pulmonary cryptococcosis . Overall, bronchoscopy yielded a diagnosis in seven of eight patients . At autopsy, two of five patients demonstrated an interstitial pattern of infection in all lobes of the lung with marked pleural thickening and giant-cell formation; two other patients showed mixed interstitial and intra-alveolar cryptococcal infiltrates . Nodal and disseminated infection were present in four patients . In patients with acquired immunodeficiency syndrome who have cryptococcal meningitis, pulmonary cryptococcal disease is common and must be distinguished from other opportunistic infections.

J Cutan Pathol, 1986 Jun, 13(3), 235 - 41
Oral "hairy" leucoplakia in an African AIDS patient; De Maubeuge J et al.; PIP: Despite differences in the modes of transmission of human immunodeficiency virus (HIV) in Africa as compared to US and Europe, the immunologic abnormalities and clinical profile in acquired immunodeficiency syndrome (AIDS) appear to be similar . Further evidence for this observation is provided by the case of a 34-year-old African male from Burundi who developed a form of oral leukoplakia previously unseen in African AIDS patients, but resembling the so-called hairy leukoplakia found in homosexuals in California . In this African patient, the diagnosis of AIDS was established on the basis of severe opportunistic infection (meningeal cryptococcosis) together with hepatic and pulmonary tuberculosis, a severely decreased T-helper to suppressor cell ratio, and the presence of antibodies to HIV . Dermatological examination revealed several mucocutaneous lesions, including 1) candidiasis with patchy depapillation of the dorsum of the tongue and 2) discrete, chronic lesions on the lateral sides of the tongue appearing as dense, white mucosal patches about 1 cm in size . A sample of a persistent white lesion on the lateral border of this patient's tongue was submitted to light and electron microscopic examination and immunoassay . The epithelium of the lingual mucosa presented parakeratotic cells, acanthosis, and surface projections typical of "hairy" leukoplakia . The prickle cells contained pyknotic nuclei and perinuclear halos . Herpes-like virus particles were observed within the nuclei of this prickle cells and in intercellular spaces . There was no evidence of papillomavirus particles . In immunoassay, the virus particles did not react to antibodies against human herpes virus . The role of herpes virus and papillomavirus in the pathogenesis of "hairy" leukoplakia has yet to be established .

Chest, 1986 Jun, 89(6), 892 - 4
Cryptococcal pneumonia in a patient with sickle cell disease; Hardy RE et al.; We present the findings in a patient having sickle cell disease who developed multilobar pneumonia . Cultures of bronchial aspirates and histologic specimens grew Cryptococcus neoformans . There was neither spontaneous clearing of the infection nor a response to bactericidal antibiotics . The patient had no underlying malignant neoplasm or immunodeficiency as indicated by history, physical examination, and specialized tests of humoral and cell-mediated immunity.

J Bacteriol, 1986 Jun, 166(3), 924 - 9
Genetic complementation in Cryptococcus neoformans; Whelan WL et al.; A complementation test was devised for the fungus Cryptococcus neoformans . Complementation was signalled by the growth of prototrophic heterokaryons generated in crosses of the type aB X Ab, where a and b represent any two of the genetic markers ilv1, cys1, cys2, and cys3 . The cloned complementing heterokaryons formed characteristic hyphal colonies that contained both hyphae and yeast cells . The heterokaryon-derived yeasts were of three kinds: parental haploids, recombinant haploids, and diploids.

Carbohydr Res, 1986 Jun 1, 149(1), 13 - 21
The effect of papulacandin B on (1----3)-beta-D-glucan synthetases . A possible relationship between inhibition and enzyme conformation; Kang MS et al.; The antibiotic, papulacandin B, inhibited growth or (1----3)-beta-D-glucan synthetase (or both) in the fungi Saccharomyces cerevisiae, Hansenula anomala, Neurospora crassa, Cryptococcus laurentii, Schizophyllum commune and Wangiella dermatitidis . No effect was observed on Achlya ambisexualis . There was no apparent correlation between the inhibition of growth and that of the synthetase . With most of the fungal extracts, the inhibition of glucan synthetase by papulacandin B became less pronounced as the substrate (UDP-glucose) concentration was decreased . At very low levels of UDP-glucose, with the enzymes from S . cerevisiae and W . dermatitidis, the antibiotic stimulated the activity of glucan synthetase . As further studied with the W . dermatitidis enzyme, those low concentrations of UDP-glucose corresponded to a sigmoidal portion of the rate vs . substrate curve . The sigmoid segment of the curve extended to higher concentrations of UDP-glucose as the temperature was increased . Concomitantly, the range of substrate concentrations at which papulacandin B stimulated the reaction or was noninhibitory was broadened . It is tentatively concluded that glucan synthetase may exist in more than one interconvertible form . The stimulatory effect of papulacandin B is possibly due to preferential binding to the active form of the enzyme . The equilibrium between these forms could be shifted by structural changes in the membrane in which the enzyme is embedded . The lack of correlation between the effects of papulacandin B in whole cells and in extracts is discussed in terms of the variations in membrane structure in the two situations.

Postepy Hig Med Dosw, 1986 May-Jun, 40(3), 331 - 46
{Acquired immunodeficiency syndrome (AIDS) in the African environment}; Kornaszewski W et al.; PIP: The characteristics of AIDS in Africa differ sharply from those in North America with respect to diagnosis and epidemiology, and in a clinical sense . The study of 78 patients treated in Kinshasa, Zaire during the period of October 1983-July 1984 yielded the following results: 159 out of a total of 1051 hospitalized patients were suspected of having AIDS, and there were 78 proven cases (54 of them died) . The average age of 40 women and 38 men was 27 and 31 years, respectively, and the ratio of married people was 35% and 74%, respectively, with a lot of men living in polygamous relationships . In the first stage of the disease weight loss appeared in 100%, recurrent diarrhea in 83.3%, significant loss of strength in 75.6%, febrile conditions in 68.3%, and skin lesions in 58.9% . The ratio of men to women was 5:5, since heterosexuality and polygamy prevailed . Cigarette smoking was the main addition, thus drug addition per se did not appear as a risk factor . Blood transfusions occurred frequently (for instance, in malaria), but hemophilic patients receiving lyophilized preparations were rare . Haitians visited in fairly large numbers after the 1960's propagating the risk of AIDS . Black Africans accounted for 100% of cases . The number of concomitant, opportunistic diseases in AIDS patients in Zaire were: 34 cases of tuberculosis, 32 cases of candidiasis, 30 fungal infections, 21 Herpes labialis and/or genitalis, 19 cases of dermal and cerebral cryptococcosis, 12 cases of cryptosporidiosis, 9 cases of Kaposi's sarcoma, 5 cases of Herpes zoster, 3 cases of aseptic cerebral infections, 3 cases of coccidiosis, 2 cases of toxoplasmosis, and 1 case of pneumonia (Pneumocystis) . Tuberculosis, cryptococcosis, cryptosporidiosis, and toxicosis were more frequent opportunistic diseases in Zaire than in the U.S.A., while pneumonia caused by Pneumocystis and Kaposi's sarcoma were relatively rare .

Farmaco {Sci}, 1986 May, 41(5), 408 - 16
{N-pyrazolyl-2-nitrobenzamides with antifungal activity}; Daidone G et al.; Novel N-pyrazolyl-2-nitrobenzamides variously substituted on the pyrazole nucleus were prepared . The products obtained together with some other N-substituted 2-nitrobenzamides were tested for their antifungal activity against Cryptococcus neoformans and Candida albicans . The results of the antimicrobial assay showed different behaviours of the organisms used with regard to the derivatives tested.

Mycopathologia, 1986 May, 94(2), 79 - 84
Non-specific immunosuppression in experimental cryptococcosis in rats; Masih DT et al.; The delayed type hypersensitivity response to human serum albumin (HSA) of rats infected intraperitoneally with 10(7) viable C . neoformans cells, and 7 days after, immunized with human serum albumin was significantly diminished (p less than 0.05) when compared with the response observed in rats immunized with human serum albumin and non infected . The spleen mononuclear cells from suppressed rats transferred to normal syngeneic recipients of the same sex suppress the afferent phase of the response (p less than 0.02) suggesting that cells present in the spleen might be one of the responsible mechanisms for the suppression to non-related antigens in infected animals.

J Am Vet Med Assoc, 1986 Apr 15, 188(8), 869 - 71
Nasal rhinosporidiosis in two dogs; Allison N et al.; Nasal rhinosporidiosis was diagnosed in 2 dogs . Cytologic criteria for diagnosis were the presence of 5- to 10-microns endospores and 50- to 1,000-microns sporangia . These findings made it easy to differentiate rhinosporidiosis from the more common nasal mycoses such as cryptococcosis . Treatment is principally surgical, but medical management can be performed if the lesion is inoperable or recurs despite multiple surgeries . Dapsone is one drug that has been used in such patients.

J Rheumatol, 1986 Apr, 13(2), 455 - 8
Cryptococcal arthritis in a patient with acquired immune deficiency syndrome . Case report and review of the literature; Ricciardi DD et al.; A patient with acquired immune deficiency syndrome (AIDS) and cryptococcal arthritis occurring in the setting of disseminated cryptococcosis is described . The literature of cryptococcal arthritis is reviewed and the association of this unusual infection with AIDS is discussed . To our knowledge, this is the first reported association between AIDS and cryptococcal arthritis.

Infect Immun, 1986 Apr, 52(1), 1 - 5
Activation of the complement system by Cryptococcus neoformans leads to binding of iC3b to the yeast; Kozel TR et al.; The complement system plays a key role in resistance to cryptococcosis . In the present study, we examined several factors that influence the binding of C3 cleavage fragments to Cryptococcus neoformans . Binding of C3 was determined by using normal human serum supplemented with 125I-labeled C3 . Incubation of encapsulated cryptococci in 20% serum led to the binding of approximately 3.2 X 10(6) molecules of C3 to each cell . The binding of C3 was markedly inhibited by heating the serum at 56 degrees C for 30 min or by chelation of the serum with EDTA . Chelation of the serum with EGTA {ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid} reduced binding of C3 by 37% . These results indicated that activation of C3 cleavage fragments and their binding to C . neoformans was primarily dependent upon the alternative pathway . Bound C3 could be removed by incubation with 1.0 M hydroxylamine (pH 10) but not by incubation with 3.5 M NaSCN or with phosphate-buffered saline containing 0.1% sodium dodecyl sulfate . These results suggested that C3 fragments were bound to C . neoformans by ester bonds . Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of C3 fragments eluted from the yeast showed the presence of protein bands consistent with the presence of iC3b . C3b was not detected on the yeast after incubation with serum for time intervals as short as 2.5 min, indicating a rapid conversion of cell-bound C3b to iC3b . These results indicate that iC3b is the ligand which most likely interacts with the phagocyte C3 receptors involved in the phagocytosis of C . neoformans.

Mycopathologia, 1986 Apr, 94(1), 27 - 30
Cryptococcus neoformans: comparisons of in vitro antifungal susceptibilities of serotypes AD and BC; Fromtling RA et al.; Thirty-nine isolates of Cryptococcus neoformans, nineteen serotype AD and twenty serotype BC, were assayed for susceptibility to eight antifungal agents using an in vitro agar dilution assay . Media employed were Kimmig agar and yeast nitrogen base supplemented with 10% glucose . The antifungal agents used were ketoconazole, amphotericin B, 5-fluorocytosine, nystatin, miconazole, BAY N 7133, ICI 153,066, and itraconazole . No clinically significant differences in vitro minimum inhibitory concentrations were detected between serotypes AD and BC against any of the compounds tested . An adverse medium effect was observed in two of the assays, but the outcome of the AD/BC comparison was not affected . This is the first report in which the in vitro antifungal susceptibilities of Cryptococcus neoformans serotypes are analyzed.

Antimicrob Agents Chemother, 1986 Apr, 29(4), 579 - 83
Comparison of itraconazole and fluconazole in treatment of cryptococcal meningitis and candida pyelonephritis in rabbits; Perfect JR et al.; Itraconazole and fluconazole, two new triazoles, were examined for their antifungal activity in rabbits . Fluconazole easily crossed the blood-cerebrospinal fluid barrier, and active drug was eliminated in high concentrations in the urine . On the other hand, itraconazole did not cross the blood-cerebrospinal fluid barrier in measurable amounts, and urine concentrations were variable . Despite differences in pharmacokinetics at the site of infection, both agents were equally effective in treating cryptococcal meningitis and candida pyelonephritis in animals . By using a ketoconazole-resistant strain of Candida albicans, we showed that there was cross-resistance in vivo between these two new triazole compounds.

Arch Dis Child, 1986 Mar, 61(3), 289 - 91
Acquired immunodeficiency with disseminated cryptococcosis; Pippard MJ et al.; A 9 year old Portuguese boy presented with severe wasting and a disseminated cryptococcal infection that resolved after massive doses of intrathecal and parenteral antifungal agents . Clinical and laboratory findings were consistent with AIDS . Apart from neonatal blood transfusions, there were no identified risk factors for HTLV III infection.

J Neurol Neurosurg Psychiatry, 1986 Mar, 49(3), 328 - 30
Cryptococcal meningitis and cerebral toxoplasmosis in a patient with acquired immune deficiency syndrome; Bahls F et al.; A 34-year-old homosexual male developed cryptococcal meningitis as the initial manifestation of Acquired Immune Deficiency Syndrome (AIDS) . With antifungal therapy he improved . Six weeks later he developed focal motor seizures and progressive hemiplegia . Computer assisted tomography revealed multiple, ring-enhancing, low density lesions . The patient expired and at necropsy he was found to have multiple toxoplasma brain abscesses as well as chronic cryptococcal meningitis . This case demonstrates that in a patient with AIDS with pre-existing central nervous system infection who develops new neurological symptoms the possibility of a second and potentially treatable infection must be considered and its diagnosis pursued vigorously.

J Am Vet Med Assoc, 1986 Mar 1, 188(5), 536 - 8
Treatment of cryptococcosis in three cats, using ketoconazole; Pentlarge VW et al.; Ketoconazole was effective in the treatment of cryptococcosis in 3 cats . A dosage of 10 to 15 mg/kg of body weight was given once or twice daily with a meal for 11 to 33 weeks . Fungal cultures and serotesting were used to assess the efficacy of treatment and resolution of active infection . In some of the cats, the treatment was associated with gastrointestinal signs and increased serum liver enzyme activity . Ketoconazole has been used in human beings, dogs, and cats for the treatment of systemic mycoses.

Arch Pathol Lab Med, 1986 Mar, 110(3), 239 - 41
Omental cryptococcoma . An unusual presentation of cryptococcosis; Chong PY et al.; A case of an omental cryptococcal granuloma, believed to be the first reported, presented as an abdominal mass in a 29-year-old man . An exploratory laparotomy revealed a soft, 8-cm lesion in the omentum . Pathologic examination showed this to be a cryptococcal granuloma containing masses of budding, encapsulated yeasts . Aggregates of eosinophils were also noted . This case is unusual in both site (as cryptococcosis tends to localize in the central nervous system) and size.

Antimicrob Agents Chemother, 1986 Mar, 29(3), 468 - 73
Canavanine resistance in Cryptococcus neoformans; Polacheck I et al.; All of the isolates of Cryptococcus neoformans var . gattii which we tested were resistant to greater than or equal to 3.5 mM canavanine . All of the serotype D isolates and 28% of the serotype A isolates of C . neoformans var . neoformans tested were susceptible to less than or equal to 18 microM canavanine, whereas the remaining 72% of the serotype A isolates were as resistant as the C . neoformans gattii isolates . In the naturally resistant isolates, the mechanism of resistance appeared to be decomposition of canavanine to a nontoxic product . However, in a resistant mutant derived from a naturally susceptible isolate, the mechanism of resistance was an impaired uptake system for canavanine . The toxic effect of canavanine in Cryptococcus results from the incorporation of canavanine into the protein component that is essential for the synthesis of proteins and RNAs.

J Clin Microbiol, 1986 Mar, 23(3), 631 - 3
Proteolytic activity of a clinical isolate of Cryptococcus neoformans; Brueske CH; A clinical isolate of Cryptococcus neoformans was grown on essential salts medium without (NH4)2SO4 and supplemented with bovine serum albumin as the sole carbon and nitrogen source . Growth on this medium resulted in secretion of proteolytic enzymes by the organism . The secretion of protease enzymes was inhibited by (NH4)2SO4 and glucose . Proteolytic activity may be a factor in virulence and pathogenicity of C . neoformans.

Surg Neurol, 1986 Mar, 25(3), 253 - 60
Septation and focal dilatation of ventricles associated with cryptococcal meningoencephalitis; Ofori-Kwakye SK et al.; A 35-year-old woman developed temporal lobe seizures . Isolated dilatation of the right temporal horn was demonstrated by computed tomography . She was asymptomatic for the next 10 months while on anticonvulsants before severe headaches, vomiting, and mental confusion prompted hospitalization . Both temporal horns were now dilated, there was marked periventricular edema, and cryptococci were cultured from the ventricular fluid . She succumbed after prolonged systemic and intrathecal antifungal therapy, having developed isolation and dilatation of both frontal horns and third and fourth ventricles . Cryptococcal or other fungal meningoencephalitis should be considered in the differential diagnosis of isolated dilatations of the ventricular chambers as noted in the present case.

Semin Respir Infect, 1986 Mar, 1(1), 45 - 52
The immunology of cryptococcal disease; Miller GP; Cryptococcus neoformans is a ubiquitous fungus found in the soil . Upon inhalation, a complex, incompletely understood series of host responses begins that determines whether the infection will be controlled or will progress to local or disseminated disease . Local pulmonary disease may be asymptomatic or may pursue a subacute course with mild pulmonary symptoms and systemic complaints suggestive of tumor . In the compromised host, however, symptomatic pulmonary disease is often the harbinger of systemic dissemination . Early host responses include phagocytosis by polymorphonuclear leukocytes aided by complement activation which provides opsonins . Lymphocytes are activated to produce lymphokines which may enhance macrophage phagocytosis and intracellular killing of ingested cryptococci . Other lymphocytes may function as natural killer-like cells or inhibit the growth of the fungus . Production of antibody further facilitates phagocytosis by both polymorphonuclear leukocytes (PMN) and monocytes (MC) . In the presence of antibody, both PMN and MC demonstrate antibody-dependent cell-mediated cytotoxicity . The combination of humoral and cell-mediated immunity in normal hosts appears to provide excellent protection against disseminated infection as evidence by the rarity of disease in exposed individuals with positive skin tests . By contrast, the frequency of cryptococcal disease in steroid-treated individuals, allograft recipients, and AIDS victims highlight the importance of T lymphocyte dependent host defenses . In view of compelling in vitro evidence for the importance of humoral responses, the infrequency of cryptococcal disease in patients with gammopathies remains a puzzle.

Semin Respir Infect, 1986 Mar, 1(1), 16 - 21
Antigen detection in the diagnosis of fungal respiratory infections; Klotz SA et al.; The diagnosis of fungal infections of the respiratory tract is often difficult and may require invasive diagnostic procedures . The detection of soluble fungal antigens in bodily fluids such as serum, pleural fluid, and bronchoalveolar lavage fluid may substantially improve the ability to diagnose fungal respiratory diseases . For instance, uncommon presentations of diseases with the pathogenic fungi, such as chronic cavitary histoplasmosis, coccidioidal empyema, and cryptococcal pneumonia are often difficult to diagnose with present techniques, and the detection of fungal antigens may prove to be more sensitive . There is an especially urgent need for sensitive, reliable, commercially available tests for the diagnosis of opportunistic fungal pneumonias that occur in immunocompromised hosts . Preliminary data holds promise for the noninvasive diagnosis of deep-seated candidiasis (including pneumonia) and pulmonary aspergillosis by the detection of fungal antigens in serum and bronchoalveolar lavage fluid . We review current techniques used for the detection of fungal antigens, including their sensitivity and specificity, and their use in diagnosing human infections.

Infect Immun, 1986 Mar, 51(3), 844 - 50
Immunoadsorption of Cryptococcus-specific suppressor T-cell factors; Mosley RL et al.; In the murine cryptococcal suppressor cell circuit, two different T-cell suppressor factors, TsF1 and TsF2, have been identified which specifically suppress the delayed-type hypersensitivity (DTH) response to cryptococcal culture filtrate antigen (CneF) . TsF1 is produced by a first-order T suppressor (Ts1) cell population and suppresses the afferent limb of the DTH response, whereas TsF2 is produced by a second-order T suppressor (Ts2) cell population and suppresses the efferent limb of the cryptococcal DTH response . The objective of this study was to ascertain whether TsF1 or TsF2 could bind to cryptococcal antigen . To assess this, adsorption of TsF1 and TsF2 was performed with heat-killed Cryptococcus neoformans cells and by solid-phase immunoadsorption (SPIA) on columns containing cryptococcal antigens, i.e., CneF covalently bound to Sepharose 4B . The suppressive effect of TsF1 was removed by adsorption with intact heat-killed cryptococci and by SPIA on CneF-Sepharose 4B . The binding of cryptococcal TsF1 to the cryptococcal SPIA column was shown to be specific since Sepharose 4B columns either coupled with Saccharomyces cerevisiae mannan or blocked with glycine did not adsorb the suppressor activity . In contrast, the suppressive component of TsF2 did not bind to heat-killed cryptococci, CneF-Sepharose 4B, S . cerevisiae mannan-Sepharose 4B, or glycine-Sepharose 4B columns . These results, together with the finding that cryptococcal antigen, anticryptococcal antibody, and C1q-binding immune complexes were not demonstrated in either TsF1 or TsF2, establish that TsF1 and TsF2 can be differentiated on the basis of their affinity for cryptococcal antigen.

Med J Aust, 1986 Feb 3, 144(3), 122 - 3
Intrapulmonary coin lesions: the changing patterns; Francis DB et al.; Of 71 intrapulmonary coin lesions seen at The Prince Charles Hospital during 1982-1984, 48 were primary pulmonary malignancies and six were metastases . There were two cases each of tuberculosis, cryptococcosis, hamartoma and granuloma . Overall, 76% of the lesions were malignant and only 3% were tuberculous . These findings contrast with those from the same institution published 20 years ago, when malignancy comprised only 38% and tuberculosis 27% of lesions . Malignancy now seems to be the major cause of coin lesions in Australia . In this survey, 82% of solitary pulmonary nodules that occurred in patients of over 50 years of age were malignant.

Ann Intern Med, 1986 Feb, 104(2), 234 - 40
Cryptococcal disease in patients with the acquired immunodeficiency syndrome . Diagnostic features and outcome of treatment; Zuger A et al.; Between 1 January 1981 and 1 December 1984, 34 of 396 patients with the acquired immunodeficiency syndrome (AIDS) developed cryptococcal infections . Twenty-six cases are reviewed . Twenty-two patients had brain or meningeal disease; the others had pulmonary disease (2 patients), pericarditis (1 patient), and antigenemia (1 patient) . During treatment, 3 patients died of cryptococcosis and 3 died of other causes . Fifteen patients were followed for more than 6 weeks after treatment . Of 8 patients who received no additional amphotericin B, 4 had relapses and died of cryptococcosis within 6 months, 3 died of other causes, and 1 survived . Of 7 patients who received maintenance therapy with amphotericin B, none had relapses, 3 died of other causes, and 4 survived . Our data suggest that maintenance therapy with amphotericin may be needed to prevent relapse in patients with AIDS.

Neurol Clin, 1986 Feb, 4(1), 159 - 70
Fungal infections of the CNS; Lyons RW et al.; Most CNS fungal infections can be divided into those that occur in normal hosts and those that occur in the immunosuppressed host . Cryptococcal infection, however, is common in both groups . The usual clinical presentation of a CNS fungal infection is chronic headache and mental status change . The CSF shows a lymphocytic meningitis with low sugar and high protein . Amphotericin B remains the drug of choice for most CNS fungal infections.

Mycopathologia, 1986 Feb, 93(2), 77 - 93
An overview of macrophage-fungal interactions; Fromtling RA et al.; A review of the literature (148 references) on the interactions of fungi with polymorphonuclear cells, monocytes and macrophages is presented . The interactions of Aspergillus species, Coccidioides immitis, Blastomyces dermatitidis, Histoplasma capsulatum, Cryptococcus neoformans, Candida albicans, and Candida species with human and experimental animal derived immune cells are examined in this overview . An effort has been made to present the reader with a comprehensive list of references with the intent of encouraging additional reading and research in this important area.

J Med Vet Mycol, 1986 Feb, 24(1), 35 - 40
Thermal death potentiation by amphotericin B in Cryptococcus neoformans and its dependence on pre-incubation temperature; Madeira-Lopes A; Thermal death of Cryptococcus neoformans in the presence of amphotericin B was strongly dependent upon the temperature of pre-incubation . The entropy coefficient, that is, the increase in entropy of activation of thermal death per square unit concentration of the drug in the medium, was 35 times higher after pre-incubation at 25 degrees C than at 39 degrees C . This means that C . neoformans cells grown at lower temperatures were much more sensitive to the temperature-dependent fungicidal effect of amphotericin B.

Eur J Clin Microbiol, 1986 Feb, 5(1), 50 - 1
Clinical isolates of Cryptococcus neoformans from Zaire; Swinne D et al.; PIP: The incidence of disseminated cryptococcosis among Central Africans with acquired immunodeficiency syndrome (AIDS) may exceed 35% . Of the 2 varieties of Cryptococcus neoformans--neoformans and gattii--it appears that the neoformans variant is the one most frequently associated with AIDS . This assumption is based on the investigation of 47 cryptococcosis isolates into white mice to determine their ability (variety gattii) or inability (variety neoformans) to produce the elongated cells characteristic of the former variety . Of the 7 isolates collected in 1951-1969, 6 were of the gattii biovar . On the other hand, all of the 40 isolates collected after 1969 were of the biovar neoformans, suggesting that the biovar gattii is disappearing from Central Africa .

Infect Immun, 1986 Feb, 51(2), 556 - 62
Antibody-dependent natural killer cell-mediated growth inhibition of Cryptococcus neoformans; Nabavi N et al.; Previous data from this laboratory indicate that normal murine nylon wool nonadherent splenic cells with characteristics of natural killer (NK) cells effectively inhibit in vitro growth of Cryptococcus neoformans, a yeastlike pathogen . Since NK cells have been shown to be involved in antibody-dependent, cell-mediated cytotoxicity against immunoglobulin G (IgG)-coated tumor cells and xenogenic erythrocytes, we were interested in assessing the effects of the IgG fraction of rabbit anticryptococcal serum on NK cell-mediated inhibition of C . neoformans growth . Early in the study it became apparent that the conventional method of determining the numbers of CFU that was used previously for assessment of viable cryptococci at the end of the growth inhibition assay was not reliable for these studies, owing to minor clumping of the organisms in the presence of anticryptococcal antibody . Therefore, the BACTEC radiometric system was evaluated and determined to be a reliable replacement for the CFU count method . Using the BACTEC methodology, we showed that the anticryptococcal antibody significantly augmented the in vitro ability of NK cells to inhibit the growth of C . neoformans compared with normal rabbit serum or tissue culture medium . Furthermore, the antibody alone did not have an adverse effect on the organism, confirming that reduced growth indices obtained from test wells containing antibody, NK cells, and cryptococci were due to the effects of the NK cells . Maximum anticryptococcal activity of the NK cells was observed in the presence of 16 micrograms of IgG per ml; however, significant augmentation of anticryptococcal activity was seen with antibody concentrations as low as 3 micrograms/ml . Using different populations of murine splenic cells which had varying degrees of NK cell activity, we were able to show that NK cell activities, as determined by 51Cr release from YAC-1 targets, directly correlated with antibody-dependent, cell-mediated growth inhibition against cryptococci, suggesting that NK cells were effector cells in the antibody-dependent assays . Furthermore, in every case, the antibody-dependent activity of NK cells against C . neoformans was higher than the spontaneous activity of NK cells against the organism, emphasizing that NK cell activity against cryptococci can be augmented by specific antibody . When NK cell numbers were enriched by Percoll fractionation of nylon wool nonadherent splenic cells, antibody-dependent and spontaneous growth inhibitory activities of the effector cells were concomitantly augmented, confirming that NK cells were the effector cells in antibody-dependent growth inhibition of cryptococci.(ABSTRACT TRUNCATED AT 400 WORDS)

Infect Immun, 1986 Feb, 51(2), 547 - 55
Correlation of natural killer cell activity and clearance of Cryptococcus neoformans from mice after adoptive transfer of splenic nylon wool-nonadherent cells; Hidore MR et al.; Previous reports demonstrate that natural killer (NK) cells inhibit the growth of Cryptococcus neoformans in vitro, but conclusive evidence supporting the effectiveness of NK cells in host resistance to cryptococci is not available . The objective of these studies was to assess the ability of NK cells to clear C . neoformans from the lungs, livers, and spleens of infected mice . CBA/J mice were depleted of NK cells, as well as other natural effector cells, by an intraperitoneal injection of cyclophosphamide (Cy), 240 mg/kg of body weight . One day later, 7.5 X 10(7) nylon wool-nonadherent (NWN) spleen cells, either untreated or treated with anti-asialo GM1 and complement to remove NK cells, were adoptively transferred to Cy-pretreated mice . On day 2 after Cy treatment, the mice were injected intravenously with 2 X 10(4) cryptococci . At 4 and 6 days after Cy treatment, tissues were assayed for NK reactivity, using a 4-h 51Cr-release assay, and for in vivo clearance of cryptococci as reflected by mean log10 CFU per organ . We observed that Cy treatment depleted NK activity against YAC-1 targets and reduced in vivo clearance of C . neoformans from the tissues of infected mice . Additionally, Cy treatment depleted the total lung and spleen cellularity and the total number of peripheral blood lymphocytes when compared with those in normal untreated control mice . Also, spleen weights were significantly decreased in comparison with those of untreated animals 4 days after Cy treatment . Adoptive transfer of untreated NWN spleen cells into Cy-depressed mice restored the NK cell activity which correlated with enhanced clearance of cryptococci from lungs, livers, and spleens . In contrast, treatment of NWN spleen cells with anti-asialo GM1 and complement before adoptive transfer abrogated the ability of these cells to restore NK activity or reduce the numbers of cryptococci present in tissues of infected mice . Taken together, these data indicate that NK cells are the cells effective in diminishing the numbers of cryptococci in tissues of infected mice . Consequently, NK cells may play a role in first-line host resistance against C . neoformans.

Nervenarzt, 1986 Jan, 57(1), 47 - 55
{Cryptococcal meningitis}; Biniek R et al.; Cryptococcal meningitis is a life-threatening disease . Headache, vomiting, cranial nerve symptoms and mental changes are the most common symptoms, but as many as 15% may have no symptoms referable to the CNS . For chemotherapy four drugs are available: namely amphotericin B, 5-fluorocytosine, miconazole and ketoconazole . Most cases have been treated by combination of amphotericin B and 5-fluorocytosine . The intrathecal administration of amphotericin B should be considered for patients who fail to respond to the usual intravenous therapy . The case is reported of a patient who died due to hydrocephalus, and the CSF-levels of the administered drugs are presented . Some pitfalls of therapy are discussed.

Clin Neuropathol, 1986 Jan-Feb, 5(1), 1 - 20
Neuropathologic findings in the acquired immunodeficiency syndrome (AIDS); Anders K et al.; The acquired immunodeficiency syndrome (AIDS) is characterized by a severe idiopathic deficiency in T-cell mediated immunity . Homosexuals, intravenous drug abusers and Haitians are predominantly affected, predisposing them to opportunistic infections and neoplasms . In this study, the central nervous system (CNS) was examined at autopsy in 29 AIDS patients . Significant CNS complications occurred in 55%, mainly related to opportunistic infections similar to those seen in patients with other causes of immunosuppression . Progressive multifocal leukoencephalopathy (three cases), cytomegalovirus (CMV) encephalitis (five cases), cryptococcal meningitis (four cases), Mycobacterium avium-intracellulare (three cases), and toxoplasmosis (one case) were found . Widespread microglial nodules were observed in 20 patients, 80% of whom had CMV inclusions elsewhere at autopsy . Primary cerebral lymphoma (one case) and lymphomatoid granulomatosis (one case) were present . Subarachnoid (five cases) and intraparenchymal (three cases) hemorrhage was seen although these were not usually clinically significant . A single case of embolic arterial obstruction with cortical infarction was due to non-bacterial thrombotic endocarditis.

Antonie Van Leeuwenhoek, 1986, 52(6), 525 - 35
Oxidation of amines by yeasts grown on 1-aminoalkanes or putrescine as the sole source of carbon, nitrogen and energy; Middlehoven WJ et al.; The maximum growth rate of Trichosporon cutaneum CBS 8111 in chemostat cultures was 0.185 h-1 on ethylamine and 0.21 h-1 on butylamine, that of Candida famata CBS 8109 was 0.32 h-1 on putrescine . The amine oxidation pattern of the ascomycetous strains studied, viz . Candida famata CBS 8109, Stephanoascus ciferrii CBS 4856 and Trichosporon adeninovorans CBS 8244 was independent of the amine that had been used as the growth substrate . It resembled that of benzylamine/putrescine oxidase found in other ascomycetous yeasts . However, differences in pH optimum and substrate specificity were observed between the amine-oxidizing systems of these three species . The amine oxidation pattern of cell-free extracts of Trichosporon cutaneum CBS 8111 varied with the amine that was used as growth substrate . The enzyme system produced by Cryptococcus laurentii CBS 7140 failed to oxidize isobutylamine and benzylamine, and showed a high pH optimum . The synthesis of amine oxidase in the four yeast strains studied was not repressed by ammonium chloride and was weakly repressed by glucose but was strongly repressed if both compounds were present in the growth medium.

Eur Neurol, 1986, 25(5), 362 - 8
Acid phosphatase activity of cerebrospinal fluid cells in bacterial and abacterial meningitis; De Reuck JL et al.; Acid phosphatase staining is performed on cerebrospinal fluid cells of 365 samples from 105 patients with various types of meningitis . This enzyme activity is strongly positive in the early samples of bacterial meningitis, as far as the patients had not received a pretreatment with antibiotics for more than 24 h . It allows monitoring the response to therapy in subsequent samples . Acid phosphatase activity is positive in 2 cases of cryptococcus meningitis . It is negative in all cases of aseptic and Mycoplasma pneumoniae meningitis . The results in herpes encephalitis are variable, depending on the clinical state and the degree of brain destruction . Acid phosphatase staining is a useful and rapid cytological technique for determination of the nature of the meningitis and for monitoring the therapeutical response.

Aust J Biol Sci, 1986, 39(1), 69 - 77
Adaptations of Drosophila and yeasts: their interactions with the volatile 2-propanol in the cactus-microorganism-Drosophila model system; Starmer WT et al.; The interactions of yeasts growing in decaying cactus tissue with and without 2-propanol were studied with respect to the costs and benefits provided to three cactophilic Drosophila species (D . mojavensis, D . arizonensis and D . buzzatii) . Two common cactus yeasts, Candida sonorensis and Cryptococcus cereanus, which can tolerate and metabolize 2-propanol, provide benefits to the three Drosophila species in the presence of the alcohol, as compared with another common cactus yeast, Pichia cactophila, which has less tolerance and cannot metabolize 2-propanol . Because 2-propanol is commonly found in decaying cactus tissue and C . sonorensis and Cr . cereanus are also frequently recovered from the rotting tissue being utilized by the Drosophila species, the interactions described here are viewed as a possible adaptation in which the yeast provides benefits to one of its vectors by metabolism of 2-propanol in the habitat.

Med Microbiol Immunol (Berl), 1986, 175(5), 307 - 16
Rapid identification of yeasts by semi-automated and conventional methods; Qadri SM et al.; Five different methods for the identification of significant yeast from clinical specimens were compared for their reliability, rapidity and cost-effectiveness . Three commercial methods consisted of semi-automated Abbott's yeasts identification system using MS-2 (Abbott Laboratories, Diagnostic Division, Irving, Texas), API 20C (Analytab Products, Inc., Plainview, NY) and Uni-Yeast-Tek (Flow Labs, Inc., MacLean, VA) . Two conventional methods included the modified dye-plur plate auxanographic and rapid tube assimilation method . The 242 coded clinical isolates used in this study included 20 species of Candida, Cryptococcus, Saccharomyces Geotrichum, Rhodotorula, Torulopsis and Trichosporon . The identification accuracies with all the systems ranges between 92.3% to 97.5% . Results were available with Abbott's MS-2 within 24 h, with rapid tube assimilation method in 6-48 h and in 72 h with other systems . Rapid tube assimilation and dye-pour-plate auxanographic methods were least expensive, with labour and material costing around $1.00 per identification, whereas the commercial system cost a little over $5.00.

Rev Neurol (Paris), 1986, 142(2), 116 - 25
{Infections of the central nervous system in malignant hemopathies}; Escudier E et al.; Central nervous system (CNS) infections in immunocompromised hosts are often accompanied by subtle disorders because immunosuppression usually decreases the inflammatory response . CNS infections in immunocompromised patients are usually caused by organisms different from those found in the general population . The organism causing CNS infection in an immunocompromised host can often be predicted if the type of immune abnormality of the patient is known . The common causes of CNS infection in immunocompromised hosts are reviewed here . Meningitis in patients with neutropenia is usually due to enteric Gram negative bacilli that live in the patient's own digestive tract . Pseudomonas aeruginosa is most common and is followed by E . Coli, Klebsiella, Enterobacter and Proteus . A major risk in patients with abnormal immunoglobulins or splenectomy is infection with encapsulated bacteria, particularly Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis . Meningitis caused by any of the encapsulated bacteria can be fulminant . Listeria monocytogenes is the most common cause of bacterial meningitis in patients with impaired cellular immunity . Nocardia asteroides is a leading cause of brain abscess in patients with hematologic malignancy . Most patients have evidence of concomitant pulmonary lesions . Fungi are among the most common organisms involving the CNS in immunocompromised hosts . Susceptible patients include those with lymphoma or leukemia and those who receive therapies aimed at suppressing delayed hypersensitivity . Cryptococcus neoformans is a common fungal cause of CNS infection in immunocompromised hosts . The primary site of infection is the lung . Spread to the CNS is via the blood stream . The clinical course is highly variable: meningitis, meningoencephalitis and focal mass lesions . Candida causes meningitis or meningoencephalitis characterized by multiple small abscesses in neutropenic hosts . Organisms reach the CNS via the blood stream usually from the digestive tract or infected intravenous catheters . Aspergillus causes brain abscess, cerebral infarction and focal meningitis in patients with neutropenia . The primary infection is in the lung . The parasites that infest the CNS of immunocompromised patients are usually those that exploit a T-lymphocyte, mononuclear phagocyte host defect . The most common are Toxoplasma gondii and Strongyloides stercoralis . There have been a few cases of amebiasis with dissemination to the brain in patients with hematologic malignancies . Toxoplasma gondii causes major CNS disease in immunocompromised hosts: meningoencephalitis or mass lesions.(ABSTRACT TRUNCATED AT 400 WORDS)

J Hepatol, 1986, 2(3), 475 - 84
The spectrum of liver disease in the acquired immunodeficiency syndrome; Gordon SC et al.; Abnormal liver chemistries, unexplained fevers, or hepatomegaly prompted 36 liver biopsies on 34 patients with the acquired immunodeficiency syndrome . The most common finding was the presence of hepatic granulomas, seen in 13 of the biopsy specimens . Eight of these granulomas were ill-defined, and 5 were more clearly associated with mycobacterial disease . Portal fibrosis and fatty infiltration were common, but a paucity of significant inflammatory activity was seen despite elevated aspartate aminotransferase levels, perhaps related to the underlying immunoincompetent status . Other noteworthy histopathologic findings included 1 patient each with peliosis hepatis and cryptococcal hepatitis . Electron-microscopic evidence of cytoplasmic tubular structures or viral particles were seen within the hepatocytes of 2 patients . It is concluded that a broad spectrum of hepatic histopathology may be seen in the acquired immunodeficiency syndrome, and that liver biopsy may be diagnostically valuable in the clinical investigation of such patients.

Eur Neurol, 1986, 25(4), 256 - 61
Cryptococcal meningoencephalitis . Case report and review of Italian literature; Bussone G et al.; A case of cryptococcal meningoencephalitis, as presented by a hypertensive hydrocephalus, is described . To our knowledge, this is the 24th case described in Italy since 1953 . The diagnosis was made with ventricular fluid examination: the patient was successfully treated with amphotericin B and 5-fluorocytosine, thus avoiding the risks of surgical treatment of hydrocephalus . Early diagnosis and proper therapy are necessary in order to decrease the high lethality of cryptococcosis.

Drugs Exp Clin Res, 1986, 12(5), 397 - 403
Therapeutic experience with ketoconazole; Difonzo EM et al.; The efficacy of ketoconazole was evaluated in forty-five patients with dermatophytoses, in twelve with candidosis, in two with fixed cutaneous sporotrichosis, in one with primary cutaneous cryptococcosis and in one with pulmonary aspergillosis . Patients received 200 mg daily of ketoconazole until complete cure, except for patients with vulvovagnitis who received 400 mg daily for five days . All patients with dermatophytoses were cured within 20 to 40 days . No recurrences were observed at post-therapy follow-up . Patients with candidosis were also cured, with only one recurrence . Patients with deep mycoses recovered, except for one with fixed cutaneous sporotrichosis, who showed slight improvement . No significant side-effects were observed during therapy . In conclusion, ketoconazole is an effective therapeutic agent for fungal infections.

Nauchnye Doki Vyss Shkoly Biol Nauki, 1986, (4), 94 - 8
{Yeast associations with mosquitoes of the genus Aedes Mg . (Diptera, Culicidae) in the Tom-Ob river region}; Frants TG et al.; The inner microflora of blood-sucking mosquitoes genus Aedes inhabiting different biotops of aspen-birch woods of the Tomsc Priob region has been investigated . 120 strains of yeasts genera Pichia, Hansenula, Saccharomyces, Torulaspora, Metschnicowia, Rhodotorula, Cryptococcus, Candida and Aueobasidium have been isolated, the most number of species belong to the genus Pichia . Yeasts P . guilliermondii, A . pullulans and M . pulcherrima have been found during all periods of insects collection . The most number of yeasts species has been found in mosquitos of mass species--A . diantaeus, A . excrucians . A . punctor and A . communis . It is supposed that isolated yeasts are collected by mosquitoes off natural substrates in the course of their development.

Bull Soc Pathol Exot Filiales, 1986, 79(4), 464 - 72
{Clinical and biological consequences of human immunodeficiency virus (LAV) infection in 15 Congolese subjects}; M'Pele P et al.; We report 15 cases of symptomatic HIV infection seen in Paris between June 1983 and June 1985 in Congolese patients . The first signs were diarrhea, weight loss, fever, pruritis . Disseminated lymphadenopathy was frequent . Twelve patients had AIDS, and the opportunistic infections were: isosporosis, oesophageal candidiasis, cerebral toxoplasmosis, Kaposi's sarcoma, CNS' cryptococcosis, cutaneo-mucosal.

Boll Ist Sieroter Milan, 1986, 65(6), 481 - 6
Clinical and epidemiological aspects of the first 50 cases of AIDS in Milan; Lazzarin A et al.; Between April 1984 and December 1985, 50 patients diagnosed as AIDS were observed in our Clinic . Risk factors were homosexuality in 21 cases (42%), drug addiction in 20 (40%), homosexuality and drug addiction in 3 (6%), haemophilia in 1 (2%) . In the remaining 5 cases the infection was acquired by vertical transmission in 2 (4%), by promiscuous heterosexual intercourse in 2 (4%) and by a single blood transfusion in 1 (2%) . Kaposi's sarcoma (KS) was the main clinical feature in 8 patients, although associated with opportunistic infections (OI) in 7 of them . A total of 91 different OI were diagnosed with a noteworthy prevalence of mycotic infections compared with OI due to other micro-organisms: 40 deep mycoses by Candida albicans, and 5 cryptococcoses . Pneumocystis carinii pneumonia (PCP) was diagnosed in 20 patients . Our data differ from the ones collected in the USA both epidemiologically, since we observed a greater incidence of AIDS in drug-addicts than in homosexuals and clinically, since in Italy a lower rate of neoplastic disease and, conversely, a higher rate of OI other than PCP are reported.

AIDS Res, 1986 Summer, 2(3), 219 - 25
Poorly encapsulated Cryptococcus neoformans from patients with AIDS . II . Correlation of capsule size observed directly in cerebrospinal fluid with that after animal passage; Bottone EJ et al.; Cryptococcus neoformans recovered from the cerebrospinal fluid (CSF) of eight patients, seven with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC), were studied to assess the relationship between degree of encapsulation noted in fresh CSF with that observed after animal passage . We further correlated encapsulation with extent of immunodeficiency in these patients . Results of these studies showed poor encapsulation (mean capsule plus cell diameter less than 10 micron) in six patients, intermediate in one (mean 15.5 micron), and full encapsulation in one (mean 24.4 micron) . The last isolate was observed in the CSF from the only patient without convincing clinical evidence for AIDS . Mouse passage of cryptococci from 5 AIDS patients and one with ARC resulted in a statistically significant (P less than 0.05) increase in capsule size over that observed directly in fresh cerebrospinal fluid . Cryptococci derived from the non-AIDS patient did not show an increase in encapsulation after mouse passage . These studies suggest that the immune deficiency state associated with AIDS exerts little selective pressure on inhaled poorly encapsulated C . neoformans.

AIDS Res, 1986 Summer, 2(3), 211 - 8
Poorly encapsulated Cryptococcus neoformans from patients with AIDS . I: Preliminary observations; Bottone EJ et al.; Ten isolates of Cryptococcus neoformans recovered from individual patients with the acquired immunodeficiency syndrome (AIDS) were studied in conjunction with three other isolates from non-AIDS patients . On primary culture nine out of ten of the AIDS isolates grew as nonmucoid, dry, pasty colonies resembling those produced by "diphtheroids." One isolate formed moist colonies . In contrast, the three non-AIDS Cryptococcus neoformans isolates produced highly mucoid colonies . India ink mounts of primary cultures of the ten AIDS isolates after 48 hours incubation in 5% CO2 showed markedly smaller capsules than the three non-AIDS isolates . India ink preparations of fresh cerebrospinal fluid of two specimens from AIDS patients in which capsule sizes were systematically determined showed a few moderately encapsulated cells dispersed among numerous others that were poorly encapsulated . This observation was confirmed in mucicarmine-stained smears of cerebrospinal fluid . Poorly encapsulated Cryptococcus neoformans seem to be associated with infections in AIDS patients.

Scand J Infect Dis, 1986, 18(3), 179 - 92
Fungal infections in patients with AIDS and AIDS-related complex; Holmberg K et al.; PIP: Persons with AIDS are predisposed to a variety of previously rare bacterial and fungal infections . Improvement in the quality and duration of survival of AIDS patients depends on the efficacy of treatment for these infections . Between 58-81% of AIDS patients contract fungal infections at some time, and 10-20% of AIDS patients die as a direct consequence of such infections . Oral candidiasis, commonly known as thrush, is the most common fungal infection among AIDS and AIDS Related Complex patients, occurring in 80-90% of cases . In a recent U.S . study, 59% of persons with oral candidiasis who were at high risk of contracting AIDS went on to develop Kaposi's sarcoma and other life- threatening infections . The most common life-threatening fungal infection experienced by AIDS patients is cryptococcosis, a disease occurring among 6% of American AIDS patients and having a mortality rate of 17% during initial infections and 75-100% on relapse . Other opportunistic infections associated with AIDS and AIDS Related Complex are bronchial candidiasis, invasive aspergillosis, disseminated histoplasmosis, and disseminated coccidioidomycosis . All are treatable but eradication i s difficult and relapse common .

Rev Neurol (Paris), 1986, 142(2), 97 - 106
{Neurologic manifestations of the acquired immunodeficiency syndrome}; Fenelon G et al.; Recognition of the neurological symptoms and signs of the acquired immunodeficiency syndrome (AIDS) since 1982 has demonstrated the involvement of the nervous system in approximately one third of the cases . Certain opportunistic infections or tumors had been previously described in the course of immunodeficiency states of other origins: cerebral toxoplasmosis, cryptococcosis, progressive multifocal leukoencephalopathy, atypical mycobacteriosis and cerebral lymphoma . Other disorders such as subacute encephalitis raise specific etiopathogenic questions . Several of these affections can be associated or succeed each other and this is the natural course in AIDS . The detection of those conditions that are curable, among which toxoplasmosis, is of primary importance.

Acta Derm Venereol Suppl (Stockh), 1986, 121, 57 - 72
Cutaneous and mucosal manifestations of the deep mycotic infections; Meyer RD; The deep mycoses are increasing in importance both as opportunistic infections and from exposure in geographically defined areas . Diagnosis may be difficult in both groups . Mucosal involvement may be non-specific (e.g., in disseminated candidiasis) or highly predictive of disseminated disease (e.g., histoplasmosis, blastomycosis and paracoccidioidomycosis) . Skin involvement is generally uncommon in disseminated aspergillosis, mucormycosis and cryptococcosis but is more common in candidemia and coccidioidomycosis . Manifestations of mucosal and cutaneous lesions of the deep mycoses are reviewed and the need for an aggressive diagnostic approach stressed . Culture is more specific than histopathologic examination alone but the latter may have to suffice in some cases . Control of underlying disease and administration of amphotericin B remain the mainstays of therapy . Ketoconazole is being evaluated as an alternative in therapy of some deep mycoses.

J Clin Microbiol, 1986 Jan, 23(1), 186 - 8
Isolation of highly encapsulated Cryptococcus neoformans serotype B from a patient in New York City; Bottone EJ et al.; For the first time, Cryptococcus neoformans serotype B was isolated from a patient in New York City, not a region endemic for B/C serotypes . The isolate was morphologically unusual, with cells several times larger in infected tissue than those characteristic of the yeastlike pathogen . This anomaly may be a problem in the identification of similar isolates . Two serotype differentiation media and a slide agglutination test were used for definitive serotype identification.

Mycopathologia, 1986 Jan, 93(1), 45 - 54
Ultrastructure of acapsular mutant Cryptococcus neoformans cap 67 and monosaccharide composition of cell extracts; Reiss E et al.; Acapsular mutant Cryptococcus neoformans cap 67 was grown in Pine's citrate broth medium for 3 days and the cells then transferred to a nitrogen-free medium for 6 days . The cells were subjected to a four stage extraction with buffered Triton-X100, cold dilute alkaline borohydride, hot dilute acetic acid, and a second alkaline extraction . Galactoxylomannan antigens were recovered from the culture supernates of both 3 day-old and 9 day-old yeast cells . The alkaline extracts contained water-soluble galactoxylomannan and a water-insoluble glucan . Dilute acid treatment released a minor amount of carbohydrate from the cells . The second alkaline extraction yielded increased amounts of glucan and galactoxylomannan from the 9 day-old cells . Soluble non-dialyzable cell extracts were antigenically identical in immunodiffusion with the culture supernate antigens . After the extraction sequence, all of the galactose, xylose, and mannose were removed from the cells . The walls retained their shape after extraction but their layers were loosened . Cells resuspended in nitrogen-free medium for six days developed thickened walls with alternating electron-dense and electron-lucent layers . The major constituent of the thickened 9 day-old cell walls was glucose, only 5% glucosamine was detected.

J Basic Microbiol, 1986, 26(1), 43 - 7
Comparative study of the temperature profiles of growth and death of the pathogenic yeast Cryptococcus neoformans and the non-pathogenic Cryptococcus albidus; Madeira-Lopes A et al.; The temperature profiles of two species of Cryptococcus were compared . The pathogenic Cr . neoformans had a maximum temperature for growth of 39.8 degrees C and the non-pathogenic Cr . albidus, of 30.2 degrees C . The specific growth rates measured in the former were of an order of magnitude higher than in the latter, whereas the Arrhenius plots of the specific thermal death rates did not show a significant difference.

J Immunol, 1986 Jan, 136(2), 672 - 80
Macrophage-mediated fungistasis in vitro: requirements for intracellular and extracellular cytotoxicity; Granger DL et al.; Macrophage cytotoxicity for Cryptococcus neoformans was investigated by culturing mouse peritoneal macrophages with a thin-capsuled clone of cryptococcus under conditions permitting efficient phagocytosis . Yeast replication was quantitated by electronic particle counting after detergent lysis of macrophages, and viability was determined by quantitative plate counts . Under appropriate conditions, reproduction was completely inhibited; stasis began at 2 hr after addition of yeasts and lasted for 30 hr . During this time organisms in medium alone proliferated rapidly, doubling their number every 2.5 hr . After removal from macrophages, 60 to 100% of macrophage-inhibited cryptococci formed colonies, indicating that the cytotoxic effect was primarily fungistatic . When yeast cells were removed from macrophages, replication recommenced within 5 hr . Supernatant medium from fungistatic co-cultures was not inhibitory for fresh yeast cells . Conditions required for complete fungistasis were 1) peritoneal macrophages induced by peptone from BCG-infected mice, 2) endotoxin in nanogram per milliliter range added to serum-containing cell culture medium, 3) confluent macrophage monolayers, and 4) macrophage:cryptococci ratios of 20 to 100:1 . Fungistasis occurred without phagocytosis but was more efficient when cryptococci were engulfed . For efficient fungistasis, macrophages must differentiate to and be maintained in the activated state . These results with yeast cells agree with the known requirements for macrophage effector function against neoplastic target cells.

Infect Immun, 1986 Jan, 51(1), 125 - 33
Development and characterization of monoclonal antibodies to Pneumocystis carinii; Graves DC et al.; Hybridoma-producing monoclonal antibodies against Pneumocystis carinii were produced by the fusion of nonsecreting mouse myeloma cells (P3X63-Ag8.653) with splenocytes from BALB/c mice that had been immunized with partially purified preparations of P . carinii . Of 227 hybridoma clones producing antibodies against P . carinii, as measured by an enzyme-linked immunosorbent assay, 12 monoclonal antibodies showing the highest reactivity in the enzyme-linked immunosorbent assay were further characterized . The majority (11 of 12) of the monoclonal antibodies did not cross-react with Candida albicans, Cryptococcus neoformans, Histoplasma capsulatum, or Mycobacterium avium as determined by absorption experiments . By using the indirect immunofluorescence assay, serological reactivity was shown for these antibodies with titers ranging from 1:40 to 1:10,240 . By using a competitive binding assay, these 12 monoclonal antibodies could be divided into seven groups, each group reacting with a different antigenic determinant of P . carinii . Sodium dodecyl sulfate-polyacrylamide gradient gel electrophoresis of P . carinii, followed by Western immunoblot analysis, allowed the identification of one major antigen with an apparent molecular weight of 110,000 by all 12 monoclonal antibodies . Other minor bands with molecular weights of approximately 116,000, 90,000, 55,000, and 35,000 were recognized by several of the monoclonal antibodies.

Acta Derm Venereol Suppl (Stockh), 1986, 121, 27 - 37
Ecology of yeast and epidemiology of yeast infections; Stenderup A; In the normal human flora yeasts occur regularly and most of them are potential pathogens . Apart from C . albicans, C . glabrata and P . orbiculare they originate mainly from sources outside man . Thus Cryptococcus neoformans has its main reservoir in pidgeon manure . The epidemiology of yeast infections and more particularly those caused by C . albicans has not been well understood until recently when 3 different methods have been developed that allow for differentiation of strains of C . albicans . These methods are based on sensitivity to various chemicals, results of various biochemical tests and the sensitivity to various killer toxins . The methods have made it possible to trace the source and spreading of C . albicans, and may prove useful also in the differentiation of other yeast species.

AIDS Res, 1986 Fall, 2(4), 343 - 8
Mycobacteria and cryptococci cultured from the buffy coat of AIDS patients prior to symptomatology: a rationale for early therapy; Damsker B et al.; Culture of the buffy coat layer of the peripheral blood of 14 AIDS patients demonstrated sustained mycobacteremia or fungemia: 11 with Mycobacterium avium-intracellulare, 2 with Cryptococcus neoformans, and one with Mycobacterium tuberculosis . The early detection of these agents prior to the onset of overt symptomatology of disseminated infection due to these microorganisms allowed speculations on an early phase bacteremia and the proposal of prompt inception of antimicrobial therapy while the microbial burden is still manageable . The method also obviates the need for more invasive techniques.

Infect Immun, 1986 Jan, 51(1), 218 - 23
Encapsulation and melanin formation as indicators of virulence in Cryptococcus neoformans; Kwon-Chung KJ et al.; Acapsular (Cap-) mutants of Cryptococcus neoformans var . neoformans that produce melanin (Mel+) on diphenol media at 30 degrees C but not at 37 degrees C were found to be avirulent for mice . Compared with wild-type isolates, the mutants had a lower rate of L-3,4-dihydroxyphenylalanine uptake at 37 degrees C and showed an insignificant level of phenoloxidase activity at both temperatures . To study the relationship of Cap and Mel phenotypes to virulence in mice, we crossed one of the mutants (Cap- Mel-) with a wild type (Cap+ Mel+) to obtain four classes of progeny (Cap+ Mel+, Cap+ Mel-, Cap- Mel+, and Cap- Mel-) . The progeny with the Cap+ Mel+ phenotype and the wild-type parent (Cap+ Mel+) were inoculated into mice (10(6) cells per mouse) and, within 40 days, produced fatal infection in 90 to 100% of the animals . None of the other three phenotypes produced fatal infection within the same period . While progeny with the Cap+ Mel- phenotype did produce fatal infection after 40 days, 70 to 90% of the mice survived at least until day 70 . However, in the isolates recovered from the brain tissue of a mouse that died on day 68, nearly 40% of the CFU had reverted to the Cap+ Mel+ type . The virulence of one of these revertant Cap+ Mel+ isolates was compared with that of a Cap+ Mel- isolate recovered from the same tissue . One hundred percent of the mice inoculated with the revertant died within 35 days, while no fatal infection was produced in the mice inoculated with the Cap+ Mel- isolate within the same period . The isolates with the Cap- Mel+ or Cap- Mel- phenotype not only failed to produce fatal infection but failed to revert to the Cap+ Mel+ type in the mouse brain during the experimental period . These results indicate that both the Cap+ phenotype and the Mel+ phenotype are important indicators of virulence in C . neoformans.

Biochim Biophys Acta, 1985 Dec 18, 826(4), 202 - 7
Molecular expression of xylanase gene in Cryptococcus albidus; Morosoli R; In the yeast Cryptococcus albidus, the utilization of xylan as compared to xylose requires at least an inducible endoxylanase enzyme, secreted in the culture medium . The endoxylanase induction was monitored by immunoprecipitation of in vivo and in vitro synthesized products . The mature endoxylanase is a highly glycosylated enzyme with an apparent molecular weight of 48 000 . Upon chemical deglycosylation with trifluoromethanesulfonic acid, the molecular weight was reduced to 40 000 . Addition of tunicamycin to the culture medium resulted in the synthesis of a modified polypeptide having a molecular weight of 40 000 . Poly(A)-containing RNA isolated from the yeast was translated in the rabbit reticulocyte protein-synthesizing system . The appearance of a translatable xylanase mRNA was observed in xylan-grown cells but not in xylose-grown cells . The polypeptide identified as xylanase had a molecular weight of 44 000 . This suggests that the xylanase is synthesized as a precursor, containing a peptide signal sequence of 35 residues.

Ann Gastroenterol Hepatol (Paris), 1985 Dec, 21(6), 389 - 91
{Gastrointestinal manifestations of AIDS}; Rene E et al.; We studied 26 cases of digestive manifestation in AIDS . The 26 patients were divided into two different epidemiological groups: 13 homosexual men, constituted the first group; no homosexual patient was in the second group which included 6 haitians, 6 africans and a pakistanian . The clinical manifestation were: a watery chronical diarrhea in 17 cases a bloody diarrhea in 2 cases; a loss of weight in the 26 cases; a dysphagia in five cases; a jaundice in one patient (due to Kaposi sarcoma of the ampulla of Vater) . The digestive lesions found, alone or associated, were necrotizing enteritis (2), ulcerative colitis (1), pseudomembranous colitis (1), candida oesophagitis (10), erythematous duodenitis (6), proctitis (4), Kaposi sarcoma (3) diffuse (2) or localized (1) . 13 patients out of the 26 presented opportunistic digestive infections due to one or several germs . The were 10 cases of oesophageal infection (due to (Candida albicans) and 8 cases of enterocolic infection due to Cytomegalovirus (3 cases), Cryptosporidium (3 cases), Mycobacterium avium intracellulare (1 case), Cryptococcus neoformans (1 case) . The other digestive infections cases were due to non opportunistic pathogens: Entamoeba histolytica (3 cases); Giardia lamblia (3 cases); Strongyloides stercoralis (2 cases); Salmonella typhi (2 cases); Shigella (1 case) . Neither the nature nor the frequency of the digestive infections was different from the first epidemiological group to the second one.

Antimicrob Agents Chemother, 1985 Dec, 28(6), 751 - 5
Comparison of amphotericin B and N-D-ornithyl amphotericin B methyl ester in experimental cryptococcal meningitis and Candida albicans endocarditis with pyelonephritis; Perfect JR et al.; Amphotericin B and N-D-ornithyl amphotericin B methyl ester were compared for therapeutic efficacies against experimentally induced cryptococcal meningitis and Candida albicans endocarditis with pyelonephritis in rabbits . Antifungal activity of the two polyenes in vitro was similar for the yeasts used in these experiments . N-D-ornithyl amphotericin B methyl ester gave a slightly higher concentration in serum than amphotericin B did, but both drugs had similar elimination curves, and penetration into the cerebrospinal fluid was poor for both . Despite these similarities between the two polyenes, amphotericin B was much more effective than N-D-ornithyl amphotericin B methyl ester in the treatment of cryptococcal meningitis in rabbits . For C . albicans endocarditis, both polyenes had similar cure rates, but in vitro measurement of fungicidal activity in serum did not predict treatment outcome . For C . albicans pyelonephritis, both polyenes showed efficacy; because higher doses of the less toxic methyl ester could be used, it sterilized the urinary tract more often than amphotericin B . These studies indicate that in vivo and in vitro experiments may be needed to predict the results of treatment with polyenes.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1985 Dec, 260(4), 566 - 71
A Cryptococcus neoformans strain from the brain of a wildlife fox (Vulpes vulpes) suspected of rabies: mycological observations and comments; Staib F et al.; A Cryptococcus neoformans strain which in 1983 caused an infection of the central nervous system (CNS) in a wildlife fox with rabies-like symptoms was tested for its strain-specific brown colour effect (BCE) on Guizotia abyssinica creatinine agar and for its ability to assimilate creatinine . Both reactions were found to be positive . These results were found to be largely identical with those of 2 out of 3 strains having caused fatal cryptococcosis in 1970, 1979 and 1983 in persons living in the area where the fox had been found (radius 40-100 km) . Some theoretical aspects of the epidemiology and pathogenesis of cryptococcosis in the wildlife fox and rodents are discussed . For further epidemiological investigations into the prevalence of Cr . neoformans in man and animals in this area, the two reactions for detecting and typing, i.e . the BCE on Guizotia abyssinica creatinine agar and the creatinine assimilation are proposed.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1985 Dec, 260(4), 550 - 65
{Experimental ocular cryptococcosis under the influence of time-limited kidney failure--a pathohistological study}; Grosse G; This animal experiment is characterized by a missing virulence of Cryptococcus neoformans strain A94 (isolated from bird manure) for the immunocompetent mouse after intraperitoneal injection and following hematogenous dissemination into all organs including the central nervous system (CNS) and by the induction of a renal failure of short duration by intramuscular injection of glycerine . In 50% of the group of 80 animals damaged in such a way ocular cryptococcosis was found in association with the selective involvement of the CNS . The involvement of the eyes was dependent on a time-limited interval between the date of infection and the date of induction of the renal failure . The partly extensive pathohistological findings in the eye, with a predominance of mycotic processes in the retina and with some cases of endophthalmitis, were found to be similar to those described in man . The animal experiment described is proposed as a model for experimental studies to resolve problems of the immunology and therapy of the ocular cryptococcosis which are of current interest.

Pathol Res Pract, 1985 Dec, 180(6), 590 - 611
Lymph node modification in patients with the acquired immunodeficiency syndrome (AIDS) or with AIDS related complex (ARC) . A histological, immuno-histopathological and ultrastructural study of 45 cases; Diebold J et al.; The authors present the results of a histopathological study on the lymph-nodes taken from 45 subjects suffering from either an AIDS or from a chronic adenopathy corresponding to the definition of AIDS related complex (ARC) . The various aspects observed were classed as type I to type IV . The lymph-node modifications observed in the 29 patients with an ARC could be divided into three principle groups: an extensive follicular hyperplasia associated with other elementary lesions or type IA (25 lymph-nodes from 23 patients); changes resembling a multicentric Castleman syndrome or type IB (1 case); angioimmunoblastic-like (AIL) lesions or type II (2 cases) and an association of lesions of type II (7 lymph-nodes from 6 patients) . During AIDS, the adenopathy usually disappears, and the small lymph-nodes removed, especially on autopsy, show an extensive lymphoid depletion (type III) with systematic sclerosis (15 lymph-nodes from 14 patients) . When adenopathy persists, it is due to infections complications (tuberculosis, cryptococcosis, avian mycobacteriosis and Whipple's disease like lesions) . Of the 10 patients in whom a Kaposi's sarcoma was observed, only 6 showed lymph-node involvement, or type IV . The different histopathological lesions seem to appear according to an evolving succession, proven by certain association of lesions and by successive biopsies . In our series, 17% of subjects with an ARC evolved to AIDS . Lymph-node biopsy allows a possible ARC to be implicated on the association of the following simple lesions: follicular hyperplasia with partial or total destruction of the perifollicular lymphocytic cisterna, infiltration of the germinative centres by streams of small lymphocytes, evolving to an aspect of a "burst" germinative centre and various sinusal reactions with, in particular, the presence of neutrophilic polynuclear cells . The biopsy also allows the forms with bad prognosis to be recognized: those with AIL-like aspect or multicentric Castleman-like syndrome, which seems to represent a particular evolutive form . Finally, it also detects, in certain cases, the localization of a Kaposi syndrome, signalling the passage to AIDS . The immunopathological studies present a double interest . Firstly, they offer arguments in favour of the diagnosis: increase in the number of T8 lymphocytes in the germinative centres with the formation of small clusters and disruption of the network of dendritic reticular cells, and the inversion of the T4/T8 ratio in the extra-follicular cortical regions, by either a decrease in T4 lymphocytes or by an increase in T8 lymphocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Fortschr Neurol Psychiatr, 1985 Dec, 53(12), 442 - 6
{Cerebrospinal fluid diagnosis of meningeal cryptococcosis}; Kaps M et al.; Cryptococcosis must be taken into account as a cause of basal meningitis . Along with a case report, clinical signs and guiding cerebrospinal fluid findings are evaluated . Special attention is paid to CSF-cytology, which provides important information in terms of identification and clinical course of the disease . For the first time C . neoformans, yielded from CSF-samples, was investigated by means of scanning electron microscopy, and compared with yeast cultured in laboratory.

J Infect Dis, 1985 Dec, 152(6), 1249 - 56
Treatment of systemic mycoses with ketoconazole: in vitro susceptibilities of clinical isolates of systemic and pathogenic fungi to ketoconazole; Shadomy S et al.; Ketoconazole was tested in vitro in three different media against 69 isolates of pathogenic fungi by using a macro-broth dilution procedure . The dimorphic systemic pathogens were highly susceptible, with most isolates of Blastomyces dermatitidis and Histoplasma capsulatum being inhibited and killed by concentrations less than or equal to 0.39 micrograms of ketoconazole/ml . Most isolates of Coccidioides immitis were also inhibited or killed by 0.39 micrograms of ketoconazole/ml; however, several were not killed by 100 micrograms/ml . Isolates of Cryptococcus neoformans and Sporothrix schenckii appeared to be less susceptible, with many isolates being resistant to less than or equal to 1.56 micrograms of ketoconazole/ml . There were 19 isolates of B . dermatitidis, C . immitis, and H . capsulatum recovered from 12 patients either during or following treatment with ketoconazole . Evidence for selection of secondary resistance to ketoconazole in these isolates was not observed . Results of these in vitro studies correlated poorly with the clinical responses to ketoconazole observed in the patients from whom the isolates were recovered.

J Clin Microbiol, 1985 Dec, 22(6), 1068 - 70
Large Cryptococcus neoformans isolated from brain abscess; Love GL et al.; Cryptococcus neoformans yeast cells 40 to 60 micron in diameter were seen in an India ink preparation made from a human brain abscess specimen . In culture at 25 degrees C, uniform 5-micron-diameter yeast cells were produced . Inoculation into mice produced yeast cells up to 40 micron in diameter, and brain heart infusion broth culture at 35 degrees C produced yeast cells about 25 micron in diameter . A relationship of yeast cell diameter to incubation temperature is suggested.

Parassitologia, 1985 Dec, 27(3), 313 - 20
{Study on the presence of yeasts in the feces of the rock pigeon (Columba livia Gmelin 1789) from rural areas}; Vidotto V et al.; The diffusion of rock-pigeon (domestic form of Columba livia Gmelin 1789) is greatly increasing owing to its high reproductivity; for this reason it is present in both countries and cities . This bird is considered an important vector of pathogens to man and domestic animals, and today it represents a serious hygienic-sanitary problem . Therefore we checked for the presence of yeasts in feces of rock-pigeons nesting in the Regional Park "La Mandria" (near Turin), visited mostly by school-children and retired . The yeasts isolated were: Candida albicans, C . krusei, C . guillermondii, C . intermedia, C . lusitaniae, C . parapsilosis, C . pseudotropicalis, C . rugosa, C . tropicalis, Cryptococcus albidus, C . laurentii, C . neoformans, C . terreus, Pichia membranaefaciens, Rhodotorula rubra, Saccharomyces cerevisiae, S . oleaginosus, S . telluris, Torulopsis candida, Trichosporon cutaneum . The incidence of the species isolated is reported on Tables 1 and 2.

No Shinkei Geka, 1985 Dec, 13(12), 1323 - 8
{ACTH dependent Cushing's syndrome with an empty sella turcica: report of three cases with emphasis on diagnostic value of selective venous sampling}; Yamamoto N et al.; Three cases of ACTH dependent Cushing's syndrome are reported with emphasis on diagnostic value of selective venous sampling . Case 1 . A 44-year-old female was admitted to our hospital with clinical diagnosis of Cushing's disease . Endocrinological examination revealed typical data of Cushing's disease . High resolution CT scan showed an empty sella turcica, and a chest film showed multi-cystic lesion in the left lower lung field . In the first trial of selective venous sampling, central to peripheral ACTH ratio (C/P ratio) was high at the superior vena cava . So, an ectopic ACTH producing lung tumor was strongly suspected . Further examinations for lung tumor were performed, and finally showed lung cryptococcosis . Therefore, selective venous sampling was performed again, and pituitary ACTH dependency was diagnosed . An eccentric pituitary microadenoma was successfully removed by transsphenoidal surgery . Case 2 . A 54-year-old female was admitted to our hospital with clinical diagnosis of Cushing's disease . In the endocrinological examinations plasma ACTH was not respond to provocation of LVP or CRF . In selective venous sampling, C/P ratios of ACTH were not greater than 2.0 at any sampling site . Further examinations showed lung tumor in the lower lobe of left lung . This tumor was surgically proved to be an ectopic ACTH producing lung carcinoid . Case 3 . A 24-year-old female was admitted to our hospital for the purpose of further examination of Cushing's disease . Three years previously exploratory transsphenoidal surgery demonstrated an empty sella without adenoma . She received postoperative radiation therapy with a dose of 5000 rad . Endocrinological examination showed typical data due to Cushing's disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Gut, 1985 Nov, 26(11), 1220 - 5
Granulomatous involvement of the liver in patients with AIDS; Orenstein MS et al.; During a one month period liver biopsy was carried out on eight patients with established acquired immune deficiency syndrome (AIDS) and two suspected of having AIDS to evaluate raised liver enzymes or unexplained fever and weight loss . Each of the 10 patients were found to have hepatic granulomas . Appropriate staining techniques showed acid-fast bacilli in seven of the liver specimens . One specimen contained numerous Cryptococcal organisms . Two biopsies showed granulomas but no organisms . Liver biopsy was found to be a high yield and rapid diagnostic procedure in patients with AIDS . Our results suggest that hepatic mycobacterial infection may be more common in the syndrome than previously recognised and that liver biopsy specimens should be examined routinely for the presence of acid-fast bacilli.

Neurology, 1985 Nov, 35(11), 1654 - 7
Fungal infections of the central nervous system: comparative analysis of risk factors and clinical signs in 57 patients; Walsh TJ et al.; Risk factors and clinical manifestations of fungal infections of the CNS were analyzed in 57 autopsied patients . Aspergillosis occurred in 16, candidiasis in 27, and cryptococcosis in 14 . Nine of 31 variables studied showed significant difference (p less than 0.01) . Cryptococcosis was community-acquired in 93%; whereas, aspergillosis and candidiasis were nosocomial in more than 95% . Focal neurologic deficits developed in 50% with CNS aspergillosis, but in only 4% with candidiasis . Meningeal signs occurred in 86% with CNS cryptococcosis, but in only 6% with aspergillosis and 7% with candidiasis . Discriminant analysis demonstrated that CNS aspergillosis was most frequently a nosocomial infection with focal neurologic deficits, pulmonary infiltrates, and hypercortisolemia . Cryptococcosis was generally a non-nosocomial infection with meningeal signs presenting in an ambulatory population . CNS candidiasis was a clinically occult nosocomial fungal infection with generally no deficits or meningismus, occurring most frequently in the neonate, the elderly, and surgical patients . The discriminant functions, which correctly classified 91% of these CNS fungal infections, may be applicable in clinical diagnosis.

J Clin Microbiol, 1985 Nov, 22(5), 856 - 7
New cause for false-positive results with the cryptococcal antigen test by latex agglutination; Boom WH et al.; The highly specific and sensitive latex agglutination test for cryptococcal antigen detection in cerebrospinal fluid is routine in many hospitals . Contamination of cerebrospinal fluid by a minute amount of syneresis fluid (surface condensation) from agar gave a strongly positive reaction which was heat stable, was not eliminated by pronase treatment, and was not detected by the normal rabbit globulin controls . These observations were valid for three commercially available test kits and could represent a preventable cause of some unexplained false-positive tests despite the use of adequate controls.

Zhonghua Min Guo Wei Sheng Wu Ji Mian Yi Xue Za Zhi, 1985 Nov, 18(4), 282 - 7
{A simple method for performing yeast carbohydrate assimilation test}; Chen L et al.; A modified auxanographic method was employed to perform carbohydrates assimilation test for 25 strains of yeasts representing the following 8 species: Candida albicans, C . glabrata, C . krusei, C . parapsilosis, C . stellatoides, C . tropicalis, Cryptococcus neoformans, and Rhodotorula glutinis . The results obtained were analyzed by comparing with the conventional auxanographic method, and it was found that the modified method was more accurate, rapid and easy in reading . The modified method was obviously easier in manipulation and more economic than that of Wickerham's broth technique and yeast assimilation agar slant technique.

Am J Clin Pathol, 1985 Nov, 84(5), 594 - 7
Adrenal pathology in the acquired immune deficiency syndrome; Glasgow BJ et al.; Adrenal pathology was examined in 41 autopsied patients with the acquired immune deficiency syndrome . This represents the largest series and the first study with quantitation of adrenal cortical necrosis . In 32 cases clinical data were analyzed for features of adrenal insufficiency . Common clinical findings included vomiting, diarrhea, fever, hypotension, and hyponatremia . None of the 32 patients showed characteristic skin hyperpigmentation . Two patients were suspected premortem to have adrenal insufficiency . In one of these patients, adrenocorticotrophic hormone (ACTH) stimulation resulted in an adequate rise in plasma cortisol values . In the other patient, the baseline plasma cortisol value was elevated and failed to rise significantly after ACTH stimulation . Pathologic findings included widespread lipid depletion, infection by cryptococcus, and acid-fast organisms consistent with Mycobacterium avium-intracellulare, involvement by Kaposi's sarcoma, and necrotizing adrenalitis due to cytomegalovirus (CMV) . A point-counting method was used to quantitate adrenal cortical and medullary necrosis . Necrosis due to CMV was greater in the medulla than the cortex . The maximum amount of adrenal cortical necrosis in any case was 70% . The degree of cortical necrosis was less than that usually associated with adrenal insufficiency.

AJR Am J Roentgenol, 1985 Nov, 145(5), 929 - 40
Cranial CT in acquired immunodeficiency syndrome: spectrum of diseases and optimal contrast enhancement technique; Post MJ et al.; A retrospective review of cranial CT scans obtained over a 4 year period in patients with acquired immunodeficiency syndrome (AIDS) and documented central nervous system (CNS) pathology is presented . The spectrum of diseases and the value of CT in detecting new, recurrent, and superimposed disease processes were determined . Fifty-one AIDS patients with confirmed CNS pathology were identified . Six of them had two coexistent diseases . Opportunistic infections predominated, especially Toxoplasma encephalitis and cryptococcal meningitis, while tumor was seen infrequently . Initial CT was positive in 76% of cases . In contrast to meningeal processes, where it was not very effective, CT was very sensitive in detecting most parenchymal disease processes . Characteristic although not pathognomonic CT patterns were found for certain diseases . Improvement or resolution of CT abnormalities in patients on medical therapy for Toxoplasma encephalitis correlated well with clinical improvement . Recurrence of CT abnormalities correlated well with medical noncompliance . The optimal contrast enhancement technique for detecting CNS pathology and for monitoring the effectiveness of medical therapy was also evaluated by a prospective study in which both immediate (IDD) and 1 hr delayed (DDD) double-dose contrast CT scans were compared . The examination found to be diagnostically superior in 30 of the 41 IDD/DDD studies was the delayed scan . It is recommended that CT be used routinely and with the 1 hr DDD scan to evaluate and follow AIDS patients with neurologic symptoms and/or signs.

Oral Surg Oral Med Oral Pathol, 1985 Nov, 60(5), 532 - 4
Oral candidiasis: forerunner of acquired immunodeficiency syndrome (AIDS)?
Chandrasekar PH, Molinari JA.
A 42-year-old man who used intravenous drugs had oral candidiasis and weight loss . Careful examination led to a diagnosis of AIDS . The patient subsequently died of disseminated cryptococcosis, systemic candidiasis, and polymicrobial bacteremia . The circumstances and progression noted in this case led to the recommendation that an aggressive screening for AIDS should be performed on patients at high risk for this syndrome who present with oral Candida infection.

N Z Med J, 1985 Oct 23, 98(789), 894 - 5
Pulmonary cryptococcosis: a report of two cases and review of the literature; Town GI et al.; Two cases of primary pulmonary cryptococcosis are described . In both cases diagnosis was established using specimens obtained at bronchoscopy and in one case confirmed by detecting cryptococcal antigen . Knowledge of the natural history of the condition allowed rational decisions to be made regarding treatment . Difficulties surrounding the diagnosis and treatment of this unusual condition are discussed.

Surg Neurol, 1985 Oct, 24(4), 437 - 40
Cerebral cladosporiosis; Kullu S et al.; A 49-year-old woman was admitted to Hacettepe Medical Faculty Hospital with the complaints of headache, nausea, vomiting, lethargy, and weakness on her right side . She revealed a history of pulmonary Cryptococcus infection 5 years before and she had been treated with amphotericin B . After clinical and laboratory investigation she was thought to have an intracranial mass, but her deteriorating situation did not allow any surgical intervention; she died within 7 days . On necropsy, hard, gray-white nodular pulmonary lesions, ranging 0.1-4 cm in diameter, basal meningitis, infarcts, and a nodular lesion 1.5 cm in diameter similar to those of the lung were present in the white matter of the right hemisphere of the brain . Microscopic examination revealed granulomatous inflammation caused by Cladosporium, which had brown pigment and septate hyphae.

Vet Immunol Immunopathol, 1985 Oct, 10(1), 33 - 69
Immunology of fungal infections in animals; Lehmann PF; The nature of immunity to fungal infection is discussed predominantly for mammals and birds . T-cell-mediated immunity seems essential for recovery both from cutaneous and mucosal infections (Candida, Malassezia and dermatophytes) and from infections of systemic fungal pathogens (Cryptococcus, Blastomyces, Histoplasma, and Coccidioides) . Often chronic progressive disease caused by these fungi is associated with a depression or absence of T-cell-mediated immunity to antigens of the infecting fungus . In contrast recovery from disease, or absence of clinical disease after exposure to these fungi, is associated with the presence of strong T-cell-mediated immune responses to the fungus . The activation of macrophages and the stimulation of epidermal growth and keratinization are the processes induced by T-cell-mediated immunity which result in the resolution of systemic or cutaneous and mucosal disease . Other cell types, for example NK cells and PMNs (polymorphonuclear leucocytes), may be important in these diseases in reducing the effective amount of inoculum to which an animal is exposed and thereby reducing the likelihood of disseminated disease . Invasive opportunistic fungi (Candida, Aspergillus, Mucorales) are resisted by PMNs which attach to the hyphae or pseudohyphae and damage them via an extracellular mechanism . Other host cell types may be important in natural resistance, fungal spores being handled by the macrophages which, under conditions when animals are not immunosuppressed, are likely to be an effective first line of defense . Subcutaneous pathogens and miscellaneous other fungal diseases are discussed from a point of view of host immunity and immunodiagnosis . Vaccine development for ringworm and for other mycoses is discussed.

Infect Immun, 1985 Oct, 50(1), 50 - 7
In vitro binding of natural killer cells to Cryptococcus neoformans targets; Nabavi N et al.; Nylon wool-nonadherent splenic cells from 7- to 8-week-old CBA mice were further fractionated on discontinuous Percoll gradients . Enrichment of natural killer (NK) cells in Percoll fractions 1 and 2 was confirmed by morphological examination, by immunofluorescent staining, and by assessing the cytolytic activity of each Percoll cell fraction against YAC-1 targets in the 4-h51Cr release assay . Cells isolated from each Percoll fraction were tested for growth-inhibitory activity against Cryptococcus neoformans, a pathogenic yeastlike organism, by using an in vitro 18-h growth inhibition assay . The results showed that NK cell enrichment was concomitant with enrichment of anti-Cryptococcus activity in Percoll fractions 1 and 2 . Cells from NK cell-rich fractions formed conjugates with the mycotic targets similar to the conjugates reported in NK cell-tumor systems . In addition, the percentage of effector cell-Cryptococcus conjugates was directly proportional to the level of the C . neoformans growth-inhibitory activity of the effector cells used . Scanning electron microscopy of the effector cell-Cryptococcus conjugates showed direct contact between the effector cells and the cryptococcal targets . An immunolabeling method combined with scanning electron microscopy was used to demonstrate that the effector cells attached to C . neoformans were asialo GM1 positive and, therefore, had NK cell characteristics.

Infect Immun, 1985 Oct, 50(1), 22 - 6
Effects of cyclosporine in experimental cryptococcal meningitis; Perfect JR et al.; We studied the effects of cyclosporine on experimental cryptococcal meningitis . Like cortisone, cyclosporine depressed the highly effective defense mechanisms of normal rabbits against inoculated Cryptococcus neoformans, causing them to develop progressive, fatal cryptococcal meningitis . Unlike cortisone, which causes a striking reduction in leukocytes in cerebrospinal fluid, cyclosporine depressed mononuclear cell function rather than numbers . Interleukin 2, a primary target for the immunodepressive action of cyclosporine, appears to be of central importance in central nervous system defenses against cryptococci . The findings suggest that humans receiving cyclosporine are likely to suffer increased incidence of cryptococcal infection.

Ann Intern Med, 1985 Oct, 103(4), 533 - 8
Cryptococcosis in the acquired immunodeficiency syndrome; Kovacs JA et al.; The clinical course and response to therapy of 27 patients with cryptococcosis and the acquired immunodeficiency syndrome were reviewed . Cryptococcosis was the initial manifestation of the syndrome in 7 patients, and the initial opportunistic infection in an additional 7 . Meningitis was the commonest clinical feature (18 patients) . Blood cultures and serum cryptococcal antigen were frequently positive . In patients with meningitis, leukocyte count, protein level, and glucose level in cerebrospinal fluid were frequently normal; cerebrospinal fluid India ink test (82%), culture (100%), and cryptococcal antigen (100%) were usually positive . Only 10 of 24 patients had no evidence of clinical activity of cryptococcal infection after completion of therapy; 6 of these 10 had relapses shown by clinical findings or at autopsy . Standard courses of amphotericin B alone or combined with flucytosine were ineffective . Cryptococcosis in patients with the syndrome is a debilitating disease that does not respond to conventional therapy; earlier diagnosis or long-term suppressive therapy may improve the prognosis.

Aust N Z J Surg, 1985 Oct, 55(5), 517 - 8
Concomitant cerebral and breast cryptococcosis; Arumugasamy N et al.; A patient with a solitary intracranial cryptococcoma of the occipital lobe of the brain and a concomitant granuloma of similar aetiology in the breast is reported . Despite resistance of the causative fungus to 5-fluorocytosine in vitro, the patient responded well to radical excisional surgery and therapy with 5-fluorocytosine.

J Clin Invest, 1985 Oct, 76(4), 1427 - 35
Defensins . Natural peptide antibiotics of human neutrophils; Ganz T et al.; We extracted a granule-rich sediment from normal human neutrophils and subjected it to chromatographic, electrophoretic, and functional analysis . The extract contained three small (molecular weight less than 3,500) antibiotic peptides that were named human neutrophil peptide (HNP)-1, HNP-2, and HNP-3, and which will be referred to as "defensins." HNP 1-3, a mixture of the three defensins, killed Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli effectively in vitro when tested in 10 mM phosphate buffer containing certain nutrients, but it had little or no bactericidal activity in nutrient-free buffer . In contrast, the nutrient-free buffer supported a high degree of activity by HNP 1-3 against Cryptococcus neoformans . In addition to its antibacterial and antifungal properties, HNP 1-3 directly inactivated herpes simplex virus, Type 1 . Two of the individual purified defensins, HNP-1 and HNP-2, were as microbicidal as the mixture HNP 1-3 . HNP-3 was less active than the other defensins against most but not all of the microbes tested . Immunoperoxidase stains revealed HNP 1-3 to have a granular localization in the neutrophil's cytoplasm by light microscopy . Frozen thin section immunogold transmission electron microscopy showed HNP 1-3 to be localized in azurophil granules . These studies define a broad-spectrum antimicrobial system in human neutrophils . The defensin system may operate in conjunction with or independently from oxygen-dependent microbicidal processes to enable human neutrophils to inactivate and destroy potential pathogens.

Clin Radiol, 1985 Sep, 36(5), 485 - 90
Cerebral torulosis: clinical features and correlation with computed tomography; Daunt N et al.; Cryptococcus neoformans (Torula histolytica) is an uncommon cause of infection in the central nervous system . We review 15 cases from all over Queensland which have presented in the last 6 years . Computed tomography (CT) studies were abnormal in 73.5%, with mass lesions and hydrocephalus being the commonest findings . Notable findings were: the disproportionate severity of clinical signs and symptoms as compared with the CT findings, which often were either normal or demonstrated only small granulomas without significant mass effect, absence of enhancement in granulomas in two cases and observation of calcification during treatment in one patient.

J Am Vet Med Assoc, 1985 Sep 1, 187(5), 508 - 9
Ketoconazole for successful treatment of cryptococcosis in a cat; Schulman J; Cryptococcosis affecting the skin and a lymph node in a 1 1/2-year-old cat was treated successfully with ketoconazole as the sole therapeutic agent . The cat was lesion-free 1 year after treatment.

Am J Otol, 1985 Sep, 6(5), 435 - 7
Cryptococcal meningitis: presentation as sudden deafness; Maslan MJ et al.; A patient presented with a bilateral profound hearing loss of sudden onset following a two-month neurologic illness . Microscopy and culture of cerebrospinal fluid revealed Cryptococcus neoformans . Treatment with amphotericin B and 5-fluorocytosine failed to restore hearing . Auditory brain stem response and electrical promontory stimulation suggest a profound deafness with poor neuronal survival . This is consistent with previous temporal bone histopathology reports in individuals dying of cryptococcal meningitis, suggesting a retrocochlear lesion . It is important to exclude this occult pathologic factor in a patient with the sudden onset of sensorineural deafness prior to embarking upon a course of steroid therapy.

J Neurol Neurosurg Psychiatry, 1985 Sep, 48(9), 853 - 8
Cryptococcal meningitis; Tjia TL et al.; Cryptococcosis is a systemic fungal disease and meningitis is the most serious complication . The purpose of this study is to define problems related to its diagnosis and treatment . This is a retrospective analysis of 25 patients admitted from January 1978 to December 1981 . All patients had cryptococcal neoformans meningitis proven by culture of cerebrospinal fluid . One patient had a predisposing illness, being on immunosuppressant therapy after a renal transplant 2 years ago . A progressively severe headache of recent onset was the most striking presentation . Fever was frequently absent as a symptom . Cranial nerve palsies were commonly seen . Impairment of consciousness and areflexia signified a poor prognosis as all four patients who died early in the course of treatment were comatose and two of them were areflexic on admission . In newly suspected cases at least 3 separate lumbar punctures are recommended as initial smears or cultures may be negative . Cerebral CT scans were abnormal in 12 patients and those with cerebral oedema or hydrocephalus had a poorer prognosis . Combined amphotericin B and 5-fluorocytosine therapy was the treatment of choice . If there is no relapse 3 years after completion of treatment, patients are considered as cured . Positive smears may remain for years after completion of treatment and retreatment is only indicated if the cultures are positive . Twenty patients are alive today and none of them have relapsed . One patient had vasculitis of both anterior cerebral arteries as a result of cryptococcal meningitis.

J Neurosurg, 1985 Sep, 63(3), 371 - 81
Surgical treatment for fungal infections in the central nervous system; Young RF et al.; The hospital records of 78 patients who underwent surgical therapy for fungal infections of the central nervous system (CNS) between 1964 and 1984 are summarized . Nine different fungal types were identified, but Coccidioides immitis and Cryptococcus neoformans accounted for most (67.1%) of the infections . A variety of clinical syndromes were seen, including chronic basal meningitis (45 patients), intracranial mass lesions (12 patients), and communicating hydrocephalus (six patients) . Thirteen patients had rhinocerebral forms of fungal infection, and two presented with spinal involvement . Delays in diagnosis were frequent and ranged from 2 months to 11 years . In 31 patients the CNS lesion was the first indication of a fungal infection, and lesion biopsy or cerebrospinal fluid (CSF) examination confirmed the diagnosis . A total of 144 surgical procedures were carried out, including lesion biopsy or excision in 13 patients, primary CSF shunting in 22, and placement of an Ommaya reservoir for administration of intraventricular or intracisternal antifungal agents in 48 . All patients received parenteral and, in some cases, intrathecal or oral antifungal chemotherapy in addition to surgical therapy . Overall mortality was 43.6% (34 deaths) . With prompt diagnosis and treatment, the mortality rate was 39% whereas, when appropriate treatment was delayed, the mortality rate was 64% . An additional 14 surviving patients (17.9%) exhibited permanent morbidity due to neurological deficits, seizure disorders, or renal toxicity following treatment with amphotericin B . The combined mortality and morbidity rate was 62.8% . Clinical symptoms were resolved completely in 29 patients, although in 10 evidence of disease persisted and chemotherapy was continued . Fungal infections of the CNS are being recognized with increased frequency . It is suggested that a high index of suspicion, aggressive attempts to obtain a diagnosis, and early and vigorous therapy may reduce the unfortunate outcome seen in a relatively high proportion of patients with CNS fungal infections.

Farmaco {Sci}, 1985 Sep, 40(9), 683 - 94
{Novel N-pyrazolylsalicylamides with antifungal activity}; Daidone G et al.; A number of new N-pyrazolylsalicylamides were prepared by fusion of phenyl salicylate and aminopyrazoles . The condensation reaction is influenced by the substitution at the C-4 position of the aminopyrazole . All the substances obtained were tested for antifungal activity against Cryptococcus neoformans and Candida albicans . It was found that their fungitoxicity is dependent on the structural feature.

J Clin Invest, 1985 Aug, 76(2), 508 - 16
Virulence of Cryptococcus neoformans . Regulation of capsule synthesis by carbon dioxide; Granger DL et al.; Cryptococcus neoformans is variably encapsulated in vitro, whereas in tissues it develops a large capsule . We observed that cells of a strain with thin capsules, when growing in a standard fungal culture medium, became heavily encapsulated when incubated in serum-free cell culture medium (Dulbecco's modified Eagle's medium {DME}) . Capsule size was quantitated physically by measuring cell volume, and chemically by determining the content of a capsular monosaccharide, glucuronate . The CO2/HCO-3 couple stimulated capsule development, resulting in visible enlargement by 3 h after exposure to high CO2/HCO-3 . The amount of capsule per cell was directly proportional to the total millimolar CO2/HCO-3 concentration between 24 and 2.4 mM at pH 7.35, but at constant PCO2 (40 torr) and varying {HCO-3}, the cells were heavily encapsulated down to pH 6.8 . Concentration of CO2/HCO-3 in the physiologic range increased elaboration of polysaccharide into the medium and slowed the cell generation time from 2 to 6 h . Four other first-passage clinical isolates were all heavily encapsulated in DME with CO2/HCO-3, but variably encapsulated in DME without CO2/HCO-3 . Exposure of yeast to increased CO2/HCO-3 caused a marked reduction in complement-mediated phagocytosis by mouse macrophages . A stable clone was isolated which contained capsular polysaccharide, but lacked the CO2-inducible phenotype . This clone was avirulent for steroid-treated rabbits . Thus, the prevailing CO2 concentration in mammalian tissues may be one stimulus for capsular polysaccharide synthesis . This could serve as an adaptive mechanism favoring parasite survival in the host.

Postgrad Med J, 1985 Aug, 61(718), 745 - 7
Disseminated cryptococcosis in a patient receiving chronic haemodialysis; Banks R et al.; Systemic infection with Cryptococcosis neoformans is described in a young man receiving maintenance haemodialysis . The organism was identified in thin sections of a cervical lymph node using resin embedding and silver staining . There were no predisposing factors other than uraemia . His clinical infection responded to the combination of oral 5-flucytosine and a total of 2.5 g of intravenous amphotericin B . He remains free of relapse after 30 months.

J Am Vet Med Assoc, 1985 Jul 15, 187(2), 169 - 70
Cutaneous cryptococcosis in three cats; Medleau L et al.; Cutaneous cryptococcosis was diagnosed in 3 cats . No other organ involvement was found . One cat has remained healthy after surgical excision of the cryptococcal skin lesion . One cat was euthanatized after diagnosis . The third cat was treated successfully with a 5-month course of ketoconazole.

Mikrobiyol Bul, 1985 Jul, 19(3), 158 - 60
{A case of Cryptococcus neoformans meningitis}; Baykal M et al.; In this paper, a fatal Cryptococcus meningitis has been reported . This type of meningitis is quite rare in this country.

Arch Intern Med, 1985 Jul, 145(7), 1237 - 40
Cerebrospinal fluid Histoplasma antibodies in central nervous system histoplasmosis; Wheat J et al.; We have evaluated the Histoplasma antibody response in the cerebrospinal fluid (CSF) in nine patients with central nervous system histoplasmosis and 98 controls . While the CSF Histoplasma antibody response identified eight of the nine patients, CSF cultures were positive in only two . Of controls with histoplasmosis but without meningitis (13 patients), or without histoplasmosis (85 patients), elevated CSF antibodies were detected by complement fixation in seven, by IgG radioimmunoassay in 17, and by IgM radioimmunoassay in five . Measurement of the CSF Histoplasma antibody response appears useful for identifying meningitis in patients with histoplasmosis, although cross-reactions occur in half of patients with other forms of chronic fungal meningitis . Patients with these other infections can usually be identified by tests for CSF Coccidioides antibodies, or cryptococcal antigens.

Arch Dermatol, 1985 Jul, 121(7), 901 - 2
Cutaneous cryptococcosis resembling molluscum contagiosum in a patient with AIDS; Rico MJ et al.; A 29-year-old Haitian man with the acquired immune deficiency syndrome (AIDS) developed disseminated cryptococcosis with an unusual cutaneous presentation . He had numerous hypopigmented papules over his face that clinically resembled molluscum contagiosum . To our knowledge, cutaneous cryptococcosis resembling molluscum contagiosum has not been previously reported . The patient had a T-cell defect consistent with AIDS and belonged to a high-risk group . To our knowledge, this is the second report of cutaneous cryptococcosis in a patient with AIDS.

Am Rev Respir Dis, 1985 Jul, 132(1), 189 - 91
Serologic diagnosis of focal pneumonia caused by Cryptococcus neoformans; Jensen WA et al.; Cryptococcal antigen was detected in the serum of 3 patients with biopsy-proved Cryptococcus neoformans pneumonitis . It is possible that the specificity of this antigen test will allow the serologic diagnosis of cryptococcal pneumonia and obviate the need for invasive procedures.

Hum Pathol, 1985 Jul, 16(7), 659 - 70
Pulmonary complications of the acquired immunodeficiency syndrome: a clinicopathologic study of 70 cases; Marchevsky A et al.; The pulmonary complications of 70 patients with the acquired immunodeficiency syndrome (AIDS) are reviewed . Pneumocystis carinii pneumonia (PCP), present in 67 per cent of the patients, was diagnosed by fiberoptic bronchoscopy with transbronchial biopsies in all of the patients except two adults, who required open lung biopsy, and two children, in whom the infection was detected only at autopsy . Other opportunistic infections, such as cytomegalovirus pneumonitis, mycobacterial infections, invasive candidiasis, toxoplasmosis, cryptococcosis, and histoplasmosis, were more difficult to diagnose by fiberoptic bronchoscopy . In only four cases were these conditions detected during life . Neoplasms and lymphoproliferative processes also presented diagnostic problems, and only one case each of Kaposi's sarcoma and lymphoid interstitial pneumonitis were detected by fiberoptic bronchoscopy . In four other cases these conditions, as well as two pulmonary lymphomas, diffuse large cell immunoblastic type, were detected only at autopsy . Sixty-eight per cent of the patients in this study died, usually with progressive intractable respiratory failure and pulmonary complications that had not been diagnosed during life, including potentially treatable diseases, such as bacterial pneumonias, PCP, nontuberculous mycobacteria, invasive candidiasis, toxoplasmosis, and invasive aspergillosis . The need for earlier detection of pulmonary complications in patients with AIDS is discussed.

Sabouraudia, 1985 Jun, 23(3), 225 - 34
Contribution of complement component C5 to the pathogenesis of experimental murine cryptococcosis; Rhodes JC; C5-deficient (C5-) mice succumb much sooner after intravenous inoculation with Cryptococcus neoformans than do C5-sufficient (C5+) mice . The C5- mice developed acute, fatal cryptococcal pneumonia, whereas the C5+ mice did not . The pneumonia was characterized by lung viable counts in C5- mice up to 1000-fold higher than in C5+, initial sequestration of twice as much 59Fe-labeled C . neoformans, and subsequent development of pulmonary edema . Chemotaxis of heterophils (PMNs) and mononuclear cells in response to C . neoformans was markedly greater in C5+ mice than in C5- animals . The effect of C5 on localization and growth of C . neoformans in the lung appeared to account for the disparate survival times of C5+ and C5+ mice after intravenous inoculation with C . neoformans.

Am Rev Respir Dis, 1985 Jun, 131(6), 952 - 5
Lymphocytic interstitial pneumonia associated with the acquired immune deficiency syndrome; Grieco MH et al.; Lymphocytic interstitial pneumonitis (LIP) is characterized by interstitial accumulation of mature lymphocytes, plasma cells, and reticuloendothelial cells and is often an unremitting process unresponsive to immunosuppressive therapy . The patient described in this report had severe candidal esophagitis and immunologic findings consistent with the acquired immune deficiency syndrome (AIDS) . There was no evidence of pulmonary infection with Pneumocystis carinii, cytomegalovirus, Mycobacterium avium-intracellulare, or Cryptococcus neoformans . Open lung biopsy revealed multiple discrete nodular foci of inflammation and alveolar inflammation . The inflammatory cells were largely lymphocytes and histiocytes . Thus, LIP may be an infrequent complication of AIDS . Epstein-Barr virus and Chlamydia trachomatis are potential etiologic agents, but a specific cause remains to be identified . This disorder has been described with a higher frequency in pediatric AIDS.

Clin Orthop, 1985 Jun, (196), 279 - 84
Spastic paraparesis due to cryptococcal osteomyelitis . A case report; Matsushita T et al.; Skeletal cryptococcosis is an uncommon infection . Isolated osteomyelitis due to Cryptococcus neoformans is quite rare . Only seven cases of skeletal cryptococcosis with involvement of vertebrae but no systemic infection have been reported . In only one was there paraplegia . Since vertebral cryptococcosis seems not to have been reported previously in Japan, this case of a 50-year-old coal miner successfully treated for paraparesis caused by cryptococcal spondylitis of the ninth, tenth, and 11th thoracic vertebrae is noteworthy . Two decompression operations and combined amphotericin B and flucytosine therapy reduced the patient's paraparesis, and no sign of recurrence was seen for 21 months after the second operation.

J Am Geriatr Soc, 1985 Jun, 33(6), 392 - 6
The role of lumbar puncture in the evaluation of dementia: the Durham Veterans Administration/Duke University Study; Becker PM et al.; The use of lumbar puncture (LP) and cerebrospinal fluid (CSF) analysis in the routine, initial evaluation of patients with dementia continues to be questioned . This is especially true in the investigation of infectious causes of dementia . To explore this question further, the authors performed a retrospective analysis of 672 hospitalized patients specifically evaluated for dementia . LP and CSF analysis were performed on 402 patients (60 per cent); routine bacteriologic, acid-fast, and fungal cultures were also obtained for 333 of these patients . Most patients were white (64 per cent) and male (63 per cent), their mean age being 66 +/- 11 years . Four patients were diagnosed as having meningitis--two with Cryptococcus neoformans, one with apparent Mycobacterium tuberculosis, and one with coagulase-positive Staphylococcus aureus . These patients were characterized by a subacute change in mental status, fever or meningismus, and CSF pleocytosis with abnormal CSF chemistries . None of the patients were found to have newly diagnosed neurosyphilis . The authors conclude that LP and CSF analysis should not be part of the routine evaluation of patients with dementia and should be performed only in the presence of such indications as a subacute duration of dementia, fever, and signs of meningeal irritation.

Ann Intern Med, 1985 Jun, 102(6), 747 - 52
Bronchoalveolar lavage and transbronchial biopsy for the diagnosis of pulmonary infections in the acquired immunodeficiency syndrome; Broaddus C et al.; The efficacy of bronchoalveolar lavage and transbronchial biopsy in diagnosing lung infection was determined in 276 fiberoptic bronchoscopic examinations done on 171 patients with known or suspected acquired immunodeficiency syndrome . Of 173 pathogens (Pneumocystis carinii, cytomegalovirus, Mycobacterium avium-intracellulare, Cryptococcus neoformans, M . tuberculosis, Coccidioides immitis, and Histoplasma capsulatum) identified during the initial evaluation or in the subsequent month, the initial bronchoscopic examination detected 166 (96%) . Bronchoalveolar lavage and transbronchial biopsy had sensitivities of 86% and 87%, respectively . When bronchoscopy included both bronchoalveolar lavage and transbronchial biopsy, the yield for all pathogens was 98% and the sensitivity for P . carinii infections was 100% . Follow-up for at least 3 weeks after examination failed to detect any additional false-negative results . Fiberoptic bronchoscopy is extremely accurate for the detection of pathogens in patients with the acquired immunodeficiency syndrome, especially when bronchoalveolar lavage and transbronchial biopsy are combined . In patients at high risk of complications from transbronchial biopsy, bronchoalveolar lavage is sufficiently accurate to be used alone.

Presse Med, 1985 May 25, 14(21), 1177 - 80
{Hepatic involvement in the acquired immunodeficiency syndrome . Study of 20 cases}; Devars du Mayne JF et al.; Liver biopsies were systematically performed in 20 patients with evidence of an acquired immunodeficiency syndrome (18 with opportunistic infections, 9 with Kaposi's sarcoma) . Hepatitis, related to hepatitis-B virus in 3 cases and to cytomegalovirus in 3 cases, was present in 6 of them . All patients had at least one of the three following lesions: non-specific portal inflammatory infiltration (6 cases), granulomatous lesions (12 cases), vascular abnormalities (12 cases) . Among hepatic granulomatous lesions: 3 were due to acid-fast bacilli and 1 to Cryptococcus . Sinusoidal abnormality included proliferation of Kupffer cells (9 cases), sinusoidal dilatation (2 cases), peliosis (4 cases) and Kaposi's sarcoma (1 case) . A relationship between these abnormalities cannot be excluded.

Klin Wochenschr, 1985 May 2, 63(9), 423 - 7
Central nervous system involvement in hairy cell leukemia; Knecht H et al.; A patient with central nervous system involvement by hairy cell leukemia is reported . Hairy cells were identified in the cerebrospinal fluid by electron microscopy and by tartrate-resistant acid phosphatase positive staining . Intrathecal treatment with methotrexate resulted in neurologic improvement, but was complicated by Cryptococcus neoformans meningitis . The leukemic phase of the disease was later successfully controlled by treatment with alpha interferon . Surface marker studies indicated a B- and T-cell phenotype of the hairy cells.

J Antimicrob Chemother, 1985 May, 15(5), 637 - 40
Penetration of aztreonam into human cerebrospinal fluid in the presence of meningeal inflammation; Greenman RL et al.; Cerebrospinal fluid of aztreonam were measured in 11 patients with meningeal inflammation . Two to eight hours after a single 2 gm intravenous dose, CSF aztreonam levels ranged from 0.76 to 16.6 mg/l . The mean CSF concentration in four patients with viral meningitis was 1.28 mg/l, which was lower than the mean concentration of 7.2 mg/l in the five with bacterial, cryptococcal or carcinomatous meningitis . Two patients with infected subdural drains were also sampled serially and had CSF levels greater than 1 mg/l between 1 and 8 h post dose . Penetration of aztreonam into the CSF in the presence of meningeal inflammation appears adequate to warrant therapeutic trials in patients infected with susceptible organisms.

Acta Neurol Scand, 1985 May, 71(5), 337 - 53
Central nervous system involvement in patients with acquired immune deficiency syndrome (AIDS); Koppel BS et al.; Central nervous system involvement occurred in 28 of 121 patients with acquired immune deficiency syndrome (AIDS) . The major risk factor in this AIDS population was intravenous drug abuse (64%) . A neurologic symptom or disability was the principal reason for hospitalization in 16 cases (57%) . Three patients had primary lymphoma of the brain and the remainder had opportunistic infections . Patients with focal neurological features usually had toxoplasmosis . Progressive headache and meningeal signs occurred with cryptococcosis . A progressive subacute dementia was probably due to cytomegalovirus . Other infections included atypical mycobacteria, candida, herpes zoster and possible progressive multifocal leukoencephalopathy.

Urology, 1985 May, 25(5), 528 - 31
Penile cryptococcosis with review of mycotic infections of penis; Perfect JR et al.; A recurrence of cryptococcosis sixteen years after the primary infection as a penile ulcer is reported . The clinical manifestations of genitourinary and skin involvement by cryptococci are discussed . The epidemiology, pathogenesis, diagnosis, and treatment of penile mycotic infections are reviewed.

Neurology, 1985 May, 35(5), 731 - 4
Cryptococcal intracerebral mass lesions: CT-pathologic considerations; Garcia CA et al.; Two patients with cryptococcal intracerebral disease showed CT evidence of multiple round hypodense nonenhancing lesions in the gray matter . These lesions proved to be gelatinous pseudocysts rather than granulomas or abscesses . Pseudocysts may occur alone or with meningitis or granulomas . Recognition of these will avoid confusion with other infectious, vascular, or neoplastic conditions.

Q J Med, 1985 May, 55(217), 169 - 72
Cure of cryptococcal infection during continued immunosuppressive therapy; Watson AJ et al.; Cryptococcus neoformans is a significant pathogen in immunosuppressed patients . In renal transplant recipients receiving prednisone, the development of cryptococcosis is associated with a poor prognosis . When such patients develop cryptococcosis they pose a particularly difficult clinical dilemma since withdrawal of prednisone, to facilitate cure of their fungal infection, may predispose to loss of their transplanted kidney . We report our experience with cryptococcal infection in 13 renal transplant patients . In 11 of these patients maintenance immunosuppression was cautiously continued to preserve allograft function . The results of our study suggest that maintenance immunosuppressive therapy may be continued throughout the period of antifungal therapy and does not preclude eradication of the infecting organisms . Our experience indicates that the prognosis for the renal transplant patient who has cryptococcosis can be improved.

J Clin Microbiol, 1985 May, 21(5), 681 - 5
Detection of a Trichosporon beigelii antigen cross-reactive with Cryptococcus neoformans capsular polysaccharide in serum from a patient with disseminated Trichosporon infection; McManus EJ et al.; Latex beads coated with anti-Cryptococcus neoformans antibody were agglutinated by serum from a bone marrow transplant recipient having a disseminated infection caused by Trichosporon beigelii . The cryptococcal latex agglutination titer in the serum of the patient rose to 1:2,560 by the time of his death . Necropsy confirmed the disseminated Trichosporon infection and absence of C . neoformans . Cell wall extracts of the isolate of the patient and two additional strains of T . beigelii agglutinated anti-Cryptococcus-coated latex beads . The antigen in the serum of the patient and in the extracts responsible for the agglutination was not destroyed by proteolytic enzymes or heat . A single antigen reactive with rabbit anti-Trichosporon serum could be identified in the serum of the patient and the cell wall extracts by rocket immunoelectrophoresis and crossed immunoelectrophoresis . Rocket immunoelectrophoresis and indirect fluorescent-antibody staining demonstrated that anti-Trichosporon antibody recognized the capsular polysaccharide of C . neoformans.

Acta Cytol, 1985 May-Jun, 29(3), 449 - 53
Disseminated cryptococcosis presenting as thyroiditis . Fine needle aspiration and autopsy findings; Szporn AH et al.; A 47-year-old diabetic ethanol and intravenous drug abuser presented with symptoms and signs indistinguishable from subacute thyroiditis . After cultures of cerebrospinal fluid grew Cryptococcus neoformans, the organism was recognized in a review of a fine needle aspirate of the thyroid . Postmortem examination documented extensive thyroid inflammation and fibrosis secondary to involvement by widely disseminated C . neoformans . Fungal infection is an uncommon cause of thyroiditis, and the need for a clinical awareness of fungal thyroiditis is emphasized, as is the need to utilize special stains to detect opportunistic infections when examining cytologic preparations from immunocompromised patients.

Infect Immun, 1985 May, 48(2), 439 - 45
Effects of first-order Cryptococcus-specific T-suppressor cells on induction of cells responsible for delayed-type hypersensitivity; Murphy JW; Cell-mediated immunity is an important aspect of host resistance against Cryptococcus neoformans . Using a CBA/J murine model, we demonstrated that injection of cryptococcal antigen (CneF) at dosages sufficient to stimulate the antigenemia observed in cryptococcosis patients induces specific T-cell-mediated suppression of the cryptococcal delayed-type hypersensitivity response . The purpose of this study was to establish whether Lyt 1+, first-order T-suppressor (Ts1) cells block the induction of T cells responsible for delayed-type hypersensitivity (TDH cells) or whether they function by inducing Lyt 2+, efferent suppressor (Ts2) cells . In one set of experiments, suppression was observed when Ts1 cells were adoptively transferred to recipient animals the day before, the day of, or the day after immunization; however, when Ts1 cells were transferred after TDH cells were present, no suppression occurred . In other experiments, putative TDH cells from lymph nodes (LN) or spleens were adoptively transferred from mice after immunization or after a suppressive dose of CneF or adoptive transfer of Ts1 cells and immunization . Delayed-type hypersensitivity could not be transferred with LN or spleen cells from mice receiving the suppressive dose of CneF or the Ts1 cells, even when the LN or spleen cells were treated with anti-Lyt 2.1 antibody and complement to remove any Ts2 cells . Delayed-type hypersensitivity was readily transferred with LN or spleen cells from immunized mice whether the cells were or were not treated with anti-Lyt 2 and complement . Furthermore, the cells in the tolerized LN cell pools responsible for suppression of TDH cell induction were Lyt 1+ 2-, I-J+ cells, which is the phenotype of the Ts1 cells . Taken together, these data indicate that Ts1 cells inhibit the induction of TDH cells . This finding, coupled with the previous demonstration that Ts1 cells or a Ts1 cell-derived soluble factor (TsF1) induces Ts2 cells, establishes that the cryptococcal Ts1 cells are bifunctional in the suppressive pathway.

Am J Clin Pathol, 1985 May, 83(5), 582 - 8
Clinical and pathologic findings of the liver in the acquired immune deficiency syndrome (AIDS); Glasgow BJ et al.; Clinical data and histologic sections of the liver, including immunohistochemical studies for hepatitis B surface and core antigens, were reviewed in 42 autopsy cases of the acquired immune deficiency syndrome (AIDS) . Hepatomegaly, elevation of serum transaminases, and mild elevation of alkaline phosphatase were commonly observed clinical and biochemical abnormalities . Mildly elevated alkaline phosphatase and normal bilirubin levels were present in patients with Mycobacterium avium-intracellulare (MAI) infection, cytomegalovirus (CMV) infection, and Kaposi's sarcoma (KS) . Histologic sections demonstrated liver involvement by MAI in eight cases; KS in six cases; cryptococcus in three cases; and CMV in two cases . One case of MAI infection was associated with marked central vein sclerosis, a finding previously unreported . Thirty-two (76%) of 42 cases had serologic or pathologic evidence of hepatitis exposure . Two patients had histologic evidence of chronic active hepatitis . The pathologic processes involving the liver appeared to be secondary to the infections and neoplasms for which this population is susceptible and did not significantly contribute to morbidity or mortality . No findings specific or pathognomic for AIDS were identified in the liver.

Pediatrie, 1985 Apr-May, 40(3), 213 - 8
{Acquired immunodeficiency syndrome in older children}; Baudoux P et al.; The authors report 3 cases of AIDS in children 10 and 11 years of age . These cases fulfill the definition of AIDS such as established by C.D.C . (Centers for Disease Control, Atlanta, Georgia U.S.A.) As opportunistic infections, the first case had oral moniliasis, the second case presented with ganglionic form of Kaposi Sarcoma and the third case had cryptococcal meningitis . The mode of transmission in this age group is unknown . Only one child had repeated transfusion . The parents of these children are in good health and were not at risk for AIDS.

Gastroenterol Clin Biol, 1985 Apr, 9(4), 327 - 35
{Digestive manifestations of the acquired immunodeficiency syndrome (AIDS): study in 26 patients}; Rene E et al.; We studied the gastrointestinal manifestations in 26 cases of AIDS . The patients belonged to two different epidemiological groups: the first group included thirteen french homosexual men, the second group included 6 Haitians, 6 Africans and a Pakistanian, none of them admit homosexual activity . The clinical manifestations were: chronic watery diarrhea in 17 cases, bloody diarrhea in 2 cases; loss of weight in the 26 cases; dysphagia in five cases; jaundice in one patient (due to Kaposi sarcoma of the ampulla of Vater) . The digestive lesions found, alone or associated, were necrotizing enteritis (2), ulcerative colitis (1), pseudomembranous colitis (1), Candida esophagitis (10), erythematous duodenitis (6), proctitis (4), Kaposi sarcoma (3), diffuse (2) or localized (1) . Thirteen patients out of the 26 presented opportunistic digestive infections due to one or several germs . These were 10 cases of esophageal infection (due to Candida albicans) and 8 cases of enterocolonic infection due to Cytomegalovirus (3 cases), Cryptosporidium (3 cases), Mycobacterium avium intracellulare (1 case), Cryptococcus neoformans (1 case) . The other digestive infections cases were due to non-opportunistic pathogens: Entamoeba histolytica (3 cases); Giardia lamblia (3 cases); Strongyloides stercoralis (2 cases); Salmonella typhi (2 cases); Shigella (1 case); Herpes simplex virus (1 case) . No difference was noticed between the homosexual and the heterosexual groups with respect to the nature and the frequency of the digestive infections.

Am J Med, 1985 Apr, 78(4), 677 - 81
Solitary pulmonary nodule due to Cryptococcus neoformans and Mycobacterium tuberculosis; Kahn FW et al.; This report describes a rare combined infection of Cryptococcus neoformans and Mycobacterium tuberculosis that manifested as a solitary pulmonary nodule in a nonimmunocompromised patient . Transthoracic needle aspiration biopsy was initially nondiagnostic, and histopathologic and culture confirmation of the diagnosis was eventually attained after wedge resection of the nodule . An extensive review of the English literature failed to reveal any reported cases of such a combined infection with a similar clinical presentation . The variable morphologic features of C . neoformans in tissue sections and the protean histologic features of pulmonary cryptococcosis can lead to diagnostic difficulties, as illustrated by this case.

Gastroenterology, 1985 Apr, 88(4), 1055 - 9
Cholangitis associated with Cryptococcus neoformans; Bucuvalas JC et al.; A 15-yr-old girl presented with complaints of right upper quadrant pain and jaundice . Elevation of serum alkaline phosphatase, signs of protal hypertension, and computed tomographic scan findings suggested a diagnosis of primary sclerosing cholangitis . However, cultures of the bile and of the common bile duct specimen obtained during a surgical procedure grew Cryptococcus neoformans . Treatment with amphotericin B was begun . An episode of upper gastrointestinal bleeding, however, led to the hepatorenal syndrome, and the patient died before antifungal therapy was completed . At autopsy, active sclerosing cholangitis associated with cryptococci involved the common bile duct . We suggest that opportunistic infection of the biliary tree should be considered in pediatric patients with presumed primary sclerosing cholangitis.

Ophthalmology, 1985 Apr, 92(4), 472 - 84
Acquired immune deficiency syndrome . Pathogenic mechanisms of ocular disease; Pepose JS et al.; A gross, light, and electron microscopic study of the eyes from 35 consecutive autopsy cases of the acquired immune deficiency syndrome revealed cotton-wool spots (71% of cases), retinal hemorrhage in areas without cytomegalovirus infection (40%), cytomegalovirus retinitis (34%) with associated retinal detachment, Roth's spots (23%), retinal microaneurysms (20%), papilledema (14%), conjunctival Kaposi's sarcoma (9%), cryptococcal chorioretinitis (6%), Mycobacterium avium-intracellulare in retina and in choroidal granulomas (6%), ischemic maculopathy (6%), bilateral keratitis (3%), and herpes simplex retinitis (3%) . Ocular infection with candida or toxoplasmosis were not found in this autopsy series . Immunocytologic studies demonstrated deposition of immunoglobulins in arteriolar walls, consistent with immune complex mediated disease . Ultrastructural studies showed a vasculopathy in the areas near cotton-wool spots . A mechanism is proposed linking the deposition of immune complexes with subsequent small vessel lesions, ischemia, cotton-wool spots and later spread of cytomegalovirus to retina via damaged vascular endothelium.

J Neurosurg, 1985 Apr, 62(4), 475 - 95
Neurological manifestations of the acquired immunodeficiency syndrome (AIDS): experience at UCSF and review of the literature; Levy RM et al.; In this review of the acquired immunodeficiency syndrome (AIDS), the authors have evaluated a total of 352 homosexual patients with AIDS or generalized lymphadenopathy managed at the University of California, San Francisco (UCSF), between 1979 and 1984 . Of an initial unselected group of 318 patients, 124 (39%) were neurologically symptomatic, and one-third already had their neurological complaints at the time of presentation . An additional 210 AIDS patients with neurological symptoms have been reported in the literature . Thus, a total of 366 neurologically symptomatic patients with AIDS or lymphadenopathy are reviewed . Central nervous system (CNS) complications, encountered in 315 patients, included the following viral syndromes: subacute encephalitis (54), atypical aseptic meningitis (21), herpes simplex encephalitis (nine), progressive multifocal leukoencephalopathy (six), viral myelitis (three), and varicella-zoster encephalitis (one) . Non-viral infections were caused by Toxoplasma gondii (103), Cryptococcus neoformans (41), Candida albicans (six), Mycobacteria (six), Treponema pallidum (two), coccidioidomycosis (one), Mycobacterium tuberculosis (one), Aspergillus fumigatus (one), and Escherichia coli (one) . Neoplasms included primary CNS lymphoma (15), systemic lymphoma with CNS involvement (12), and metastatic Kaposi's sarcoma (three) . Cerebrovascular complications were seen in four patients with hemorrhage and five with infarction . Five patients in the UCSF series had multiple intracranial pathologies, including two cases of simultaneous Toxoplasma gondii infections and primary CNS lymphoma, two cases of coexistent Toxoplasma gondii and viral infections, and one case of combined Toxoplasma gondii and atypical mycobacterial infection . Cranial or peripheral nerve complications, seen in 51 patients, included cranial nerve syndromes secondary to chronic inflammatory polyneuropathy (five), lymphoma (five), and Bell's palsy (five) . Peripheral nerve syndromes included chronic inflammatory polyneuropathy (12), distal symmetrical neuropathy (13), herpes zoster radiculitis (six), persistent myalgias (two), myopathy (two), and polymyositis (one) . In light of the protean behavior of AIDS and the problems related to the clinical, radiological, and serological diagnosis of the unusual and varied associated nervous system diseases, patients with AIDS and neurological complaints require a rigorous and detailed evaluation . The authors' experience suggests that biopsy of all CNS space-occupying lesions should be performed for tissue diagnosis prior to the institution of other therapies.

Arq Neuropsiquiatr, 1985 Mar, 43(1), 29 - 38
{Neurocryptococosis and immunosuppression: experimental model in mice}; Machado LR et al.; In order to accomplish a model for immunosuppression in experimental conditions two lots of 50 young mice were divided into groups of 10, and submitted to dexamethasone ingestion . Two experiments were considered in the study . In the first experiment conditions for immunosuppression were established in 50 mice, by per os supply of several concentrations of dexamethasone in the water given for normal daily intake ad libitum . Criteria of immunosuppression considered include: hair standing on end; leukopenia by decrease of lymphocyte population; spleen atrophy in relation to controls, with severe hypoplasy of all lymphoid structures . In the second experiment another lot of 50 mice in similar conditions established for the first experiment and concerning the immunosuppression were submitted to intraperitoneal inoculation of near 10(6) Cryptococcus neoformans . Culture suspensions of cryptococci isolated from cerebrospinal fluid samples of human neurocryptococcosis cases were used for this purpose . Although fungi could be recognized in lungs, liver and spleen from every mice inoculated, only those with central nervous system involvement (near by an half of all) died . The discussion included considerations about the role of the blood-brain barrier function in the findings registered.

Med Clin North Am, 1985 Mar, 69(2), 333 - 44
Cryptococcal infection of the central nervous system; Sabetta JR et al.; The pathogenesis, clinical signs and symptoms, laboratory manifestations, and laboratory diagnosis of cryptococcal infection of the central nervous system are reviewed, as well as the interaction between the organism and the immune system of the host . In addition, based on our own experience and that of others, the therapy and prognosis of cryptococcal meningitis are discussed.

J Am Coll Cardiol, 1985 Mar, 5(3), 703 - 6
Cardiac lesions in acquired immune deficiency syndrome (AIDS); Cammarosano C et al.; Autopsy findings in 41 patients with acquired immune deficiency syndrome (AIDS) were reviewed . Major pathologic findings in the heart were demonstrated in 10 cases, and metastatic Kaposi's sarcoma in either the epicardium or myocardium was revealed in 4 cases, including 1 with additional fibrinous pericarditis . Nonbacterial thrombotic endocarditis with embolization to major organs was found in three cases, isolated fibrinous pericarditis of unknown origin was found in two and Cryptococcus neoformans myocarditis was found in one case . The primary cause of death in eight cases was pulmonary or systemic infection . Two patients died of thromboembolic disease . These findings suggest that cardiac lesions in AIDS relate to both morbidity and mortality.

J Bacteriol, 1985 Mar, 161(3), 1231 - 2
Occurrence of diploid strains of Cryptococcus neoformans; White CW et al.; A mating between niacin and pantothenate auxotrophs of Cryptococcus neoformans gave a few prototrophic progeny that were self-fertile . These were uninuclear but contained twice as much DNA as the parental strains . Segregation of nutritional markers was observed upon sporulation . We conclude that these self-fertile strains are diploids.

J Bacteriol, 1985 Mar, 161(3), 1188 - 94
Stimulation of beta(1----3)glucan synthetase of various fungi by nucleoside triphosphates: generalized regulatory mechanism for cell wall biosynthesis; Szaniszlo PJ et al.; Particulate fractions from the taxonomically diverse fungi Achlya ambisexualis, Hansenula anomala, Neurospora crassa, Cryptococcus laurentii, Schizophyllum commune, and Wangiella dermatitidis were found to catalyze the time-dependent incorporation of glucose from UDP-{14C}glucose into a water-insoluble material . The reaction was stimulated by bovine serum albumin . The product was characterized as beta(1----3)glucan on the basis of its resistance to alpha- and beta-amylase and susceptibility to beta(1----3)glucanase . With the exception of the preparation from A . ambisexualis, all others were stimulated by nucleoside triphosphates and their analogs . The best activators were GTP and guanosine 5'-(gamma-thio)triphosphate . It is concluded that the stimulation by nucleotides, previously found with the glucan synthetase of Saccharomyces cerevisiae, is a regulatory mechanism that was well conserved during fungal evolution, presumably because of its importance in controlling cell wall biosynthesis and cell growth.

Acta Cytol, 1985 Mar-Apr, 29(2), 157 - 61
Fine needle aspiration cytology of granulomatous cryptococcosis of the lung; Silverman JF et al.; A cryptococcal infection was diagnosed in a patient with a history of immunoblastic non-Hodgkin's lymphoma by fine needle aspiration (FNA) cytology of a pulmonary nodule . This case illustrates that granulomatous inflammation can be appreciated by FNA cytology and, when seen, should result in a search for the specific organism . This case also reemphasizes the value of FNA cytology in the management and follow-up of patients with malignancy or those being treated with chemotherapy.

Acta Cytol, 1985 Mar-Apr, 29(2), 154 - 6
Diagnosis of unsuspected pulmonary cryptococcosis with sputum cytology; Gupta RK; This paper describes our experience in the sputum cytology diagnosis of pulmonary cryptococcosis, the clinical diagnosis of which is usually difficult . The cytologic findings are described briefly along with other pertinent supportive data, and the importance of sputum cytology in the diagnosis of this clinically occult mycotic disease is emphasized . The cytologic examination of deep cough samples of sputum in cases with an appropriate clinical setting and pulmonary infiltrates not only can be a rewarding procedure but also can result in the institution of an appropriate line of treatment for the possible prevention of widespread dissemination.

Acta Cytol, 1985 Mar-Apr, 29(2), 151 - 3
Cytologic detection of Cryptococcus neoformans in cerebrospinal fluid . Rapid screening methods; Brown RW et al.; Yeasts of Cryptococcus neoformans in cerebrospinal fluid (CSF) were studied using polarized light and fluorescence microscopy . Ultraviolet-induced fluorescence of wet-fixed, Papanicolaou-stained smears and polarization of air-dried, Diff-Quik or Leishman-stained preparations are complementary methods that allow for rapid screening for and immediate identification of Cryptococcus in cytologic preparations of CSF.

Sabouraudia, 1985 Feb, 23(1), 37 - 45
Chemotactic activity of cerebrospinal fluid in experimental cryptococcal meningitis; Perfect JR et al.; Cerebrospinal fluid from rabbits with chronic cryptococcal meningitis was tested for its chemotactic activity towards polymorphonuclear cells and monocytes . CSF chemotactic activity was present; it peaked 5-8 days after infection, coinciding with the time when the number of inflammatory cells in CSF was greatest . However, little chemotactic activity could be found in the early stages of infection, during the initial ingress of inflammatory cells . The chemotactic activity appeared to be host-derived, with characteristics consistent with lymphokine(s) or C5a . Treatment with cortisone significantly reduced the CSF chemotactic activity for both cell types; this reduction may contribute to the severe CSF leukopenia observed in cortisone-treated animals, which are unable to eradicate this yeast infection . Modulation of CSF chemotactic activity may be important to the success or failure of the host central nervous system response to Cryptococcus neoformans.

Ann Rheum Dis, 1985 Feb, 44(2), 126 - 7
Cryptococcal sacroiliitis; Brand C et al.; Disseminated cryptococcal disease is known to occur in patients with altered immune status . We have reported an unusual case of cryptococcal disease manifested solely by sacroiliitis, which occurred in a patient on chronic steroid therapy for autoimmune haemolytic anaemia . This case stresses the importance of considering unusual organisms as a cause of sepsis in patients with altered immune status.

Hum Pathol, 1985 Feb, 16(2), 121 - 8
Pulmonary cryptococcosis; McDonnell JM et al.; Observation of an unusual pulmonary distribution of cryptococci in a patient at autopsy prompted a review of 36 patients with pulmonary cryptococcosis listed in the autopsy files of The Johns Hopkins Hospital . The patients ranged in age from 2 to 89 years (mean, 49 years), 19 were female, and 18 were black . All but three patients had underlying debilitating diseases, and 23 patients had received steroids and/or chemotherapy . In 25 patients (69 per cent) cryptococcosis was a major factor contributing to death, through pulmonary disease in ten, systemic involvement in seven, and central nervous system disease in eight . In 15 patients (42 per cent) cryptococcosis was diagnosed clinically . Four basic morphologic patterns were observed: 1) Seven patients (19 per cent) had one or more peripheral pulmonary granulomas . In three of these patients the granulomas were apparently quiescent, and no other lesions were found . 2) Nineteen patients (53 per cent) had what has been called granulomatous pneumonia, with intra-alveolar proliferating organisms and varying degrees of inflammatory response, which, when present, ranged from acute inflammation to diffuse intra-alveolar granulomas with giant cells . 3) In seven patients (19 per cent) organisms were present diffusely within alveolar capillaries and interstitial tissues, and reactions ranged from little or no inflammation with numerous organisms to few organisms with miliary granulomas . 4) In three patients (8 per cent) both intra-alveolar and intravascular organisms were present in massive numbers, and the primary route of infection was uncertain . Fatalities from pulmonary and generalized infection occurred in patients in each histologic group . The results show marked variability both in pathologic reaction to cryptococci and in the clinical appreciation and significance of pulmonary cryptococcosis.

Sabouraudia, 1985 Feb, 23(1), 77 - 80
Production and regeneration of protoplasts from Cryptococcus; Rhodes JC et al.; Protoplasts were quickly and efficiently produced from both varieties of Cryptococcus neoformans and from C . laurentii by use of the multi-enzyme product Novozym 234 . Conditions for regeneration of protoplasts are described . DNA yield from the Novozym-produced protoplasts was superior to that from snail gut enzyme-derived protoplasts.

Antonie Van Leeuwenhoek, 1985, 51(3), 289 - 301
Yeast species utilizing uric acid, adenine, n-alkylamines or diamines as sole source of carbon and energy; Middelhoven WJ et al.; Yeast strains utilizing uric acid, adenine, monoamines or diamines as sole source of carbon and energy were isolated from several soil samples by the enrichment culture method . The most common species was Trichosporon cutaneum . Strains of Candida catenulata, C . famata, C . parapsilosis, C . rugosa, Cryptococcus laurentii, Stephanoascus ciferrii and Tr . adeninovorans were also isolated . All strains utilizing uric acid as sole carbon source utilized some primary n-alkyl-l-amines, hydroxyamines or diamines as well . The ascomycetous yeast strains showing these characteristics all belonged to species known to assimilate hydrocarbons . Type strains of hydrocarbon-positive yeast species which were not found in the enrichment cultures generally assimilated putrescine, some type strains also butylamine or pentylamine, but none assimilated uric acid . Methanol-positive species were not isolated . Type strains of methanol-positive and of hydrocarbon-negative species did not assimilate uric acid, butylamine or putrescine . Assimilation of putrescine as sole source of carbon and energy may be a valuable diagnostic criterion in yeast taxonomy.

Allergy, 1985, 40 Suppl 3, 17 - 20
Mould spores and yeasts in outdoor air; Rantio-Lehtimaki A; Most inviable spore counts of outdoor air in Europe are based on Burkard spore trap results . For viable counts different kinds of slit samplers and Andersen sampler are used . Results of viable and inviable sampling methods are not completely comparable, but the results complete each other . Spore frequencies in outdoor air are almost equal in different Nordic countries . Cladosporium is the most important spore type everywhere . In South Finland it accounts for ca . 85% of viable and ca . 50% inviable spore counts . The frequencies are lower in the country than in town . Cladosporium frequencies decrease northwards so that in Lapland the percentage is only ca . 5 and the maxima are 1/4-1/5 of those in South Finland . The frequencies of Alternaria spores are 4-5 times lower in Nordic countries than in Middle Europe . E.g . in Turku weekly maxima have been ca . 250 spores X m-3, in the country even lower . Penicillium accounts for ca . 4% of all colonies in viable counts in South Finland, Botrytis 2%, and yeasts also ca . 2% . The most important yeasts are Cryptococcus albidus, Cr . laurentii, Sporobolomyces roseus and Rhodotorula species . Actinomycetes very seldom occur on culture plates, only 0.02% of all.

Dermatologica, 1985, 171(5), 357 - 61
Primary cutaneous cryptococcosis; Baes H et al.; A 53-year-old man, a pigeon fancier, with long-standing asthma, treated for years with systemic corticosteroids, developed a fast-growing mass on his right wrist . The diagnosis of cryptococcosis was established by histology and culture of tissue which yielded Cryptococcus neoformans . Oral treatment with ketoconazole for 3 months resulted in a complete cure with residual hyperpigmentation and minute scars . During a 10-month follow-up, the patient was free of recurrences.

Antonie Van Leeuwenhoek, 1985, 51(2), 139 - 50
Production, purification and partial characterization of an endo-polygalacturonase from Cryptococcus albidus var . albidus; Federici F; Cryptococcus albidus var . albidus produced an extracellular endo-polygalacturonase (poly (1,4-alpha-D-galacturonide) glycanohydrolase EC 3.2.1.15) when grown in a synthetic medium containing one of a variety of pectic substances or galacturonic acid . The highest level of enzyme activity (15.5 VU X ml-1) was obtained after 72 h of growth on 1.0% low-methoxyl pectin . The enzyme, purified by gel filtration (Sephadex G-100) after repeated ammonium sulphate precipitation and dialysis, showed only one band by polyacrylamide gel electrophoresis and had the following properties: mol wt (MWr) 41000 dal; isoelectric point (pI) = 8.10 +/- 0.10; optimum temperature and pH for activity around 37 degrees C and pH 3.75, respectively; pH stability in the pH range 4.0 to 8.0; complete heat inactivation after 10 min at 55 degrees C; Km and Vmax values 5.7 X 10(-1) mg X ml-1 and 5.1 X 10(-1) mmoles X min-1, respectively.

Ann Acad Med Singapore, 1985 Jan, 14(1), 16 - 21
Intracerebral cryptococcomas; Arumugasamy N; Cerebral cryptococcomas are not unusual and occurred in 7.8% of our cases of cryptococcal meningitis . This warrants a careful lookout for it if treatment is to be prompt and effective . CAT Scanning has proved to be an important adjunct in investigative exclusion of such instances . Although cerebrospinal fluid shunting proved to be of great importance in patients with demonstrable hydrocephalus, total surgical extirpation of the granuloma when demonstrated would appear to be essential, if cure is to be assured . 5-Fluorocytosine continues to be the drug of choice although recent indications of resistance to it are real . Modifications to antifungal chemotherapy will hence have to be judiciously made . Agglutination studies, besides typing, have indicated their usefulness in this regard, in the management of our cases.

Trans R Soc Trop Med Hyg, 1985, 79(1), 67 - 9
Cryptococcosis in Zimbabwe; Gould PR et al.; The records of 16 consecutive patients with proven cryptococcosis, admitted to the two referral hospitals in Harare over a 15-year period, were reviewed . 15 were cases of meningitis, one with spinal cord granuloma, and the 16th was an orbital osteomyelitis . There were eight children and eight adults with a marked male preponderance . There was an absence of any predisposing conditions . The common clinical signs and symptoms were headache, neck stiffness, fever, confusion or drowsiness, cranial nerve lesions and long tract signs . The diagnosis was rarely suspected on admission but was discovered during life in 15 patients, in 12 by finding the organism in the (CSF) cerebrospinal fluid, and in three by biopsy of affected tissue . 50% of patients presented with a predominance of polymorphs in the CSF . The mortality rate was very high (57%) but most died before adequate treatment could be given.

Infect Immun, 1985 Jan, 47(1), 288 - 93
Genetic resistance to murine cryptococcosis: the beige mutation (Chédiak-Higashi syndrome) in mice; Marquis G et al.; The influence of the bgJ and bg2J mutations on the susceptibility of mice to experimental cryptococcosis was studied in inbred mice of the C57BL/6J and C3H/HeJ strains . Although infected animals with the bg/bg genotype had a significantly shorter lifespan than bg/+ or +/+ animals, C3H/He beige-2J mice were less susceptible than C57BL/6 beige-J mice when compared with nonbeige mice of similar background . On days 18 and 19 after infection, quantitation of cryptococci in the brain, liver, and spleen revealed that the overall burden of organisms in infected C57BL/6 beige-J mice was in excess of one log unit above that found in the brain, liver, and spleen of infected C57BL/6 +/+ mice . At that time, C57BL/6 beige-J mice showed a 53% increase in mean brain weight, a 67.8% decrease in mean liver weight, and a 58.6% decrease in mean spleen weight, when compared with uninfected animals of the same age and genetical lineage . The corresponding figures for C57BL/6 +/+ mice were a 32% increase in mean brain weight, a 41.4% decrease in mean liver weight, and a 23.4% decrease in mean spleen weight . From these data, it is concluded that the beige mutation in mice is associated with increased susceptibility to cryptococcosis, the accrued susceptibility of the beige mutant is related to more rapid changes in the weight profile of the target organs as well as to a higher rate of growth or decreased clearance of Cryptococcus neoformans or both, and other autosomal genes are likely to be involved in the genetic control of susceptibility to murine cryptococcosis.

J Urol, 1985 Jan, 133(1), 61 - 4
Do the imidazoles have a role in the management of genitourinary fungal infections?
Wise GJ, Goldberg PE, Kozinn PJ.
The imidazoles have demonstrated antifungal activity against a number of fungi that are pathogenic for man . Effective clinical use has been demonstrated in patients with cutaneous and systemic candidiasis, aspergillosis, blastomycosis, coccidioidomycosis, cryptococcus and systemic candidiasis, aspergillosis, blastomycosis, coccidioidomycosis, cryptococcus and histoplasmosis . We report our experience with the oral imidazole agent ketoconazole in the management of 8 patients with significant urinary candidiasis as judged by elevated urinary candidal counts (greater than 15,000/ml.) . Only 4 of the 8 patients had resolution of candiduria with ketoconazole therapy . Intravenous miconazole, another imidazole, has been available for treatment of systemic and genitourinary fungal infections . Limited success (50 per cent) with intravenous miconazole has been noted in the treatment of systemic candidiasis with urinary involvement . Miconazole also has been used as a systemic and local irrigant in the treatment of bladder and renal candidiasis . Based on these observations and our own studies, we believe that the imidazoles have a limited role in the management of patients with significant fungal involvement of the urinary tract.

Microbiol Immunol, 1985, 29(10), 981 - 91
Chemical characterization of capsular polysaccharide from Cryptococcus neoformans serotype A-D; Ikeda R et al.; During a study of serotyping of Cryptococcus neoformans, we found that the type strain of C . neoformans (CBS 132) was serotype A-D . This strain agglutinated with both factor 7 serum (specific for serotype A) and factor 8 serum (specific for serotype D) in our serotyping system . Therefore, we investigated the chemical structure of the antigenic capsular polysaccharide of this strain . The soluble capsular polysaccharide was obtained from the culture supernatant fluid by precipitation with ethanol . Column chromatography of the polysaccharide on DEAE-cellulose yielded three fractions (F-1 to F-3) . The major antigenic activity was found in the F-3 fraction . The results obtained by methylation analysis, controlled Smith degradation-methylation analysis, partial acid hydrolysis, and other structural studies of F-3 polysaccharide indicated that the polysaccharide contains mannose, xylose, and glucuronic acid at a ratio of 7:2:2, and has a backbone of alpha (1-3)-linked D-mannopyranoside residues with a single branch of beta (1-2)-xylose and glucuronic acid . The ratio of mannose residues with or without a branch in the F-3 polysaccharide was 4:3 and its molecular weight calculated from the average of the degree of polymerization was 46,500 daltons . These results indicate that the chemical structure of the capsular polysaccharide of serotype A-D is very similar to those from serotypes A and D, suggesting that small differences in the molar ratio and pattern of linkage of monosaccharides in the branch of the polysaccharides of the three serotypes may be responsible for their different specificities.

Microbiol Immunol, 1985, 29(6), 517 - 32
Characterization of pathogenic constituents of Cryptococcus neoformans strains; Kagaya K et al.; We examined seven strains, comprising five serotypes, of Cryptococcus neoformans to determine what constituents of the organisms are responsible for pathogenicity and virulence in BALB/c mice . C . neoformans strains were divided into three virulence classes by survival rates after intravenous inoculation of 1 X 10(5) or 1 X 10(7) viable cells, and virulence was found not to be correlated with serotype or capsular size . C . neoformans cells resisted phagocytosis in different degrees in the presence of normal serum . Sensitivity of the C . neoformans strains to singlet oxygen ranged from resistance to susceptibility . Histological examination revealed that a weakly encapsulated virulent strain induced inflammatory responses with granuloma formation in the liver, lung, and kidney in addition to formation of cystic foci in the brain . In contrast, although the heavily encapsulated virulent strain produced granulomatous lesions in the liver, this strain preferably produced mucinous cystic foci in the lung, kidney, and brain . Correlation between virulence, and biological, histopathological and physiological evidence suggests that C . neoformans strains are endowed with the implicated multiple pathogenic constituents in various degrees and proportions . The following are suggested as the most important pathogenic constituents: a polysaccharide capsule responsible for resistance to phagocytosis and formation of cystic foci; a cell surface structure for responsible for resistance to intra- or extracellular killing and induction of the granulomatous lesion; a growth rate suitable for interacting with phagocytic elimination.

Mycopathologia, 1985 Jan, 89(1), 5 - 12
Ultrastructure of Cryptococcus neoformans in the cerebrospinal fluid of a patient with cryptococcal meningitis; Hiruma M et al.; The ultrastructure of Cryptococcus neoformans in the cerebrospinal fluid, which was obtained from a patient suffering from systemic lupus erythematosus and cryptococcal meningitis, before treatment and on the 10th and 20th day after the start of treatment was studied . Numerous cryptococci were detected in their cerebrospinal fluid before treatment . However, in most of them their biological activity was low and their organelles were not clear . A few yeasts preserved well their organelles . Such cells showed a tendency to develop vesicular membrane structures (lomasomes) touching the internal part of the cell wall . In the cerebrospinal fluid on the 20th day all of the yeasts were dead, even though numerous yeasts were observed by an India-ink method . At this time no colonies were recovered from the fluid.

Infect Immun, 1985 Jan, 47(1), 282 - 7
Genetic resistance to murine cryptococcosis: increased susceptibility in the CBA/N XID mutant strain of mice; Marquis G et al.; In a survey of 301 normocomplementemic inbred mice (belonging to nine different strains: BALB/cN nu/nu and nu/+, CBA/N, C57BL/KsJ, C57BR/cdJ, CBA/CaJ, BRVR, DW/+, and C57BL/6J) for natural resistance to Cryptococcus neoformans, cumulative survival values were found to range from 12 to 22 days . When the average organ weights of infected animals were compared with reference values obtained in uninfected mice of the same age and genetic lineage, the following changes were documented . In the CBA/N strain, the mean spleen and brain weights increased 313 and 13.5%, respectively, whereas the mean liver weight remained unchanged . In the CBA/Ca strain, cerebral cryptococcosis was the dominant clinical feature, and a 54% increase in mean brain weight was recorded at the time of death . The averaged liver weight was drastically lower, whereas spleen weight values evinced a biphasic pattern of transient splenomegaly followed by involution . At the median time of death, CBA/N mice had significantly more cryptococci in the liver and spleen than corresponding CBA/Ca mice . In the (CBA/N X CBA/Ca)F1 mice, susceptibility to C . neoformans segregated according to the sex-linked inheritance of the X-linked immunodeficiency (xid) gene . It is concluded that (i) susceptibility to cryptococcosis is under multigenic control, (ii) the xid locus on the X chromosome influences susceptibility to cryptococcosis, and (iii) xid mice behave differently than CBA/Ca mice in their organ response during the course of the infection.

Clin Exp Neurol, 1985, 21, 271 - 81
Cryptococcal infection of the central nervous system; Sandstrom PA; Two patients with cryptococcal infection of the central nervous system are described . These cases illustrate the variability in mode of presentation of this disease . Upon diagnosis, both patients were initially treated with a combination of amphotericin B and 5-fluorocytosine . Despite an early clinical and serological response, limiting side effects occurred in both cases and 5-fluorocytosine treatment was terminated . In Case 2, 5-fluorocytosine therapy was reinstituted at lower dosages later in the course of the illness, with good results . Combination therapy is superior to amphotericin B alone . However, to circumvent significant toxicity problems close monitoring of renal function, peripheral blood counts and serum 5-fluorocytosine levels are essential . Treatment is usually administered for a minimum of six weeks and remission is assessed on clinical, mycological and serological grounds . Thereafter, adequate follow-up is mandatory.

Clin Exp Neurol, 1985, 21, 263 - 70
Ophthalmological complications of cryptococcal meningitis; Blackie JD et al.; Two patients with cryptococcal meningitis associated with ophthalmological complications are described . One patient developed a cryptococcal fundal lesion which disappeared during chemotherapy . Chronically raised intracranial pressure was associated with a visual field defect . This resolved with repeated lumbar punctures . The second patient developed visual deficits secondary to papilloedema and responded to optic nerve decompression . In both cases CT scanning demonstrated swelling of the optic nerves . In the second patient this regressed after decompression . A review of the variety of the ophthalmological complications of cryptococcal meningitis and their prevalence is presented . The risk of developing severe visual disability is assessed.

J Clin Invest, 1985 Jan, 75(1), 1 - 3
The acquired immunodeficiency syndrome (AIDS); Rosen FS; PIP: This article discusses clinical, immunologic, and etiologic considerations in the acquired immunodeficiency syndrome (AIDS) and the relationship of AIDS to other immunodeficiency diseases . The outstanding clinical feature of AIDS is the occurrence of opportunistic infections in individuals with no prior known cause of immunodeficiency . Such infections have included Pneumocystis carinii, oral thrush from Candida albicans, cytomegalovirus, atypical mycobacteria, cryptosporidium, and Herpes simplex virus . Central nervous system invasion by Cryptococcus neoformans and Toxoplasma gondi has also been reported . Persistent quantitative and functional depression of T4 cells is the immunologic hallmark of full-blown AIDS . Another prominent feature is in vitro spontaneous hyperactivity of B cells . AIDS patients lose cutaneous delayed hypersensitivity reactions both to recall and to new antigens, and T-cell-mediated cytotoxicity is diminished . The mounting number of T8 cells and diminution in T4 cells causes an inversion in the normal T4:T8 ratio . It has been hypothesized that the host defense mechanism is the attempt of the cytotoxic T8 cells to destroy the virus-infected T4 cells . 2 groups of investigators have discovered a lymphocytotropic retrovirus from blood and node lymphocytes of AIDS patients: lymphadenopathy-associated virus (LAV) or human T-lymphotropic virus type III (HTLV-III) . Among the primary immunodeficiencies, AIDS most closely resembles the defect observed in purine nucleoside phosphorylase deficiency, an inherited autosomal recessive phenomenon . There is evidence that multiple infections or antigen overload characterize all the risk groups for AIDS . Moreover, antigen overload in experimental animals and man has been shown to suppress immune responses and to down-regulate Ia antigen expression on monocytes . This may prove to be a necessary precondition for the development of AIDS .

J Immunol, 1985 Jan, 134(1), 577 - 84
Regulation of cell-mediated immunity in cryptococcosis . III . Characterization of second-order T suppressor cells (Ts2); Murphy JW et al.; Frequently, patients with systemic cryptococcosis have depressed or absent in vivo or in vitro cell-mediated immune responses to cryptococcal antigen . In addition, these patients have relatively high levels of circulating cryptococcal antigen, which is generally considered indicative of a poor prognosis . Because acquired cell-mediated immunity is an important host defense mechanism in cryptococcosis, we have been studying the effects of cryptococcal antigen on such responses . Using a murine model, we have demonstrated that cryptococcal antigen given i.v . to CBA/J mice, to simulate antigen levels found in patients, can trigger the production of a series of suppressor cells that specifically inhibit anticryptococcal cell-mediated immune responses . Briefly, cryptococcal antigen induces afferent suppressor and/or suppressor inducer (Ts1) cells in the lymph nodes of mice, and the Ts1 cells, or a soluble factor derived therefrom (TsF1), stimulate the production of second-order or efferent suppressor (Ts2) cells . This report provides data that demonstrate that the Ts2 cells were induced in spleens from cyclophosphamide (Cy)-resistant precursors in response to cryptococcal Ts1 cells or TsF1 and that a proliferative process sensitive to Cy was not required for Ts2 induction . The Ts2 cells were detectable 6 days after Ts1 injection, were specific in suppressing the cryptococcal delayed-type hypersensitivity (DTH) response, were T cells with an Lyt-1-,2+,Ia+ (I-J+) phenotype, were effective only on the efferent limb of the cryptococcal DTH response, and mediated their activity via a soluble factor (TsF2) . Thus far, the suppressive pathway induced by cryptococcal antigen has characteristics more like those of the suppressor circuits described for the DTH responses to the haptens azobenzenearsonate and 4-hydroxy-3-nitrophenyl acetyl than those of the modulating circuits induced by other antigens . We postulate that a suppressive circuit similar to the one we have defined in the mouse model is operating to suppress the in vivo and in vitro cell-mediated immune responses in cryptococcosis patients who have significant amounts of circulating cryptococcal antigen.

J Emerg Med, 1985, 3(4), 275 - 9
Acquired immunodeficiency syndrome manifested as disseminated cryptococcosis; Pittard G et al.; A 32-year-old male homosexual presented to the emergency department (ED) with the clinical picture of a nonspecific illness . While in the ED, he experienced a first-time seizure . Computed tomography (CT) showed an enhancing mass lesion . Antibacterial therapy was started and continued until a second lumbar puncture (LP), 36 hours after admission, showed distinct yeast forms . Subsequent institution of appropriate therapy did not prevent the patient's death . The cause of death was disseminated cryptococcosis secondary to acquired immunodeficiency syndrome (AIDS).

Acta Neuropathol (Berl), 1985, 66(3), 188 - 98
Neuropathologic observations in acquired immunodeficiency syndrome (AIDS); Sharer LR et al.; Neuropathologic changes are described in eight fatal cases of the acquired immunodeficiency syndrome (AIDS), including four subjects who were i.v . drug abusers (two women, two men), two Haitian men, one bisexual man, and one women who had no known risk factors for AIDS . All cases had significant infections of the brain, with examples of bacterial, fungal, protozoal, and viral disease in the group . Combined infections were observed in three cases, including one case of previously unreported central nervous system (CNS) abscess due to Nocardia (combined with Salmonella) . The most frequent CNS pathogen was Toxoplasma gondii, which in both Haitian subjects co-existed with systemic tuberculosis, leading to diagnostic difficulty . Only one case of "subacute encephalitis" was represented, although in other cases microglial nodules were associated with Toxoplasma and Cryptococcus organisms, as well as probable cytomegalovirus . Non-infectious complications included a cerebral infarct (one case), central pontine myelinolysis (one case), and diffuse microcystic change of the white matter (one case).

Mycopathologia, 1984 Dec 30, 88(2-3), 127 - 30
Effect of cyclophosphamide on rats experimentally infected with Cryptococcus neoformans; Riera CM et al.; This study was undertaken to establish the function of T-lymphocytes in protective immunity against a cryptococcal infection in animals treated with Cyclophosphamide (Cy) pre or post infection and to determine how they relate to the progression of the disease . Inbred Suquia rats were infected either intranasally (i.n.) or intraperitoneally (i.p.) with 10(5) viable Cryptococcus neoformans cells . The infected rats were divided in three groups . One of the groups (group I) was utilized as a control . The second group (group II) was treated with Cy 3 days before the infection . The third group (group III) was treated with Cy 3 days after the infection . At approximately 22 days post infection, C . neoformans growth in selected organs of all animals were determined . In addition, humoral and delayed-type hypersensitivity (DTH) response were assayed in the rats . When the Cy was applied after the infection the DTH was significantly diminished and inverse to the colony forming unit (CFU) which increased leading to the animals death . On the other hand, injection of the drug 3 days before infection did not modify the response, that was comparable in both treated and the control animals . In this study it were found haemagglutinating antibodies in sera from i.n . and i.p . infected rats although at minimal levels and were not present in all animals . The results show that with a low T-cell function induced as a consequence of injecting Cy after the infection, rats did not develop a normal DTH response to cryptococcal infections and were not able to control a cryptococcal infection as well as animals with normal T-cell function.

FEBS Lett, 1984 Dec 10, 178(2), 323 - 6
Glycosidic bond rearrangements in isomeric xylobioses by yeast xylan-degrading enzymes; Biely P et al.; The cells of Cryptococcus albidus induced for xylan-degrading enzymes are capable of transforming 1,2-beta-xylobiose and 1,3-beta-xylobiose into 1,4-beta-xylobiose, the natural inducer . The conversion involves transglycosylation and hydrolysis catalyzed by beta-xylosidase and beta-xylanase . A probable intermediate of the conversion of 1,2-beta-xylobiose was isolated and identified as a trisaccharide, 4-O-beta-xylopyranosyl-2-O-beta-xylopyranosyl-D-xylopyran ose . The trisaccharide is cleaved by purified endo-1,4-beta-xylanase of C . albidus mainly at the 1,2-beta-linkage yielding xylose and 1,4-beta-xylobiose.

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