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Biomedical subjects

R Negroni

Publications and source records attributed to R Negroni.

At least 37 records · Page 2Linked to original sources
PubMed1997

Cryptococcosis associated with AIDS in the Muñiz Hospital of Buenos Aires.

Some epidemiologic, diagnostic and immunologic aspects of 93 (75 males and 18 women) cases of cryptococcosis (CRY) associated with AIDS, hospitalized in the Muñiz Hospital (MH) in Buenos Aires during 1994, were retrospectively studied. The median age (MA) of the patients under study was 28 years (17-49 y); 30 (17-49) y for males and 23 (22-34) y for women. Intravenous drug addiction (34% of patients) and homo/bisexuality in men (17%) were the most frequent risk factors for HIV infection. The MA of these groups were 27.5 (17-41) y and 34 (25-41) y, respectively. Microscopic CSF examination with India ink and the blood cultures (lysis-centrifugation) achieved the diagnosis of CRY in 67 (72%) and 16 (17%) patients, respectively. At diagnosis, the median titers for Cryptococcus neoformans capsular antigen were 1/1,000, 1/100 and 1/1 in serum, CSF and urine, respectively. Sixty five strains of C. neoformans were insolated from clinical samples; all were identified at variety neoformans employing the culture medium proposed by Salkin & Hurd and the D-proline assimilation test. At diagnosis, CD4+ lymphocytes counts were < 50/microliter in 46 patients (83.63%), and were between 51 and 200/microliter in 9 (16.4%). The CD4+/CD8+ ratio was < 1 in all patients. Most patients were born (83%) and lived at diagnosis (96%) in Buenos Aires (Bs As) city, Bs As outskirts towns and cities located in Bs As province.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Study of some lymphocyte subset counts and cytokine levels in cryptococcosis associated with AIDS.

Approximately 100 new cases per year of cryptococcosis in HIV+ patients are observed in Muñiz Hospital, 35% of them suffer a fatal outcome within the first four weeks after diagnosis in spite of treatment. Apparently there is not a useful parameter that allows a clear prediction of this early fatal outcome of the disease. The aim of this study is to determine some cytokine levels and several lymphocyte subpopulations counts in order to correlate these results with the evolution of the disease. Forty HIV+ patients suffering culture confirmed cryptococcosis were enrolled in this study, 8 HIV+ patients without cryptococcosis and 8 healthy individuals with negative serology for HIV were included as controls. The following determinations were done in all cases: CD3+, CD4+, CD8+, CD16+CD3-, CD19+ cell counts, IL-1; IL-12, TNFalpha in serum and TNFalpha in CSF. Ten cases with cryptococcosis and AIDS were controlled three months after treatment. The average of CD4+ and NK cell counts in patients before treatment were 22/microl and 90/microl respectively; IL-1 levels were higher in the patients than in the healthy control group, conversely IL-12 levels did not show significant differences in the three studied groups. Serum concentrations of TNFalpha were higher in patients than in the control group and were not modified after treatment, conversely antifungal medication diminished IL-1 concentration and remarkably increased NK cell counts. At the same time antigen levels in serum and CSF decreased. The results obtained seem to show that the immunological alterations observed in these patients are those characteristically exhibited in severe HIV disease and that some parameters such as CD8+ cell counts lower than 200/microl, less than 50 CD4+/microl, more than 50 pg/ml of TNF-alpha and serum capsular antigen titer higher than 1:5000 seem to predict a rapidly fatal course of infection.

Journal Article↗
PubMed1993

Itraconazole: pharmacokinetics and indications.

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

Humans↗
PubMed1993

Cryptococcosis produced by a urease negative strain of Cryptococcus neoformans.

A urease negative strain of Cryptococcus neoformans was isolated form a patient with AIDS. The identification of the yeast was confirmed by physiological and pathogenicity tests. Clinically, the disseminated cryptococcal infection in our patient was identical to those reported in other patients with AIDS.

AIDS-Related Opportunistic Infections↗
PubMed1992

Comparative study of six antifungal treatments in an experimental model of murine cryptococcosis.

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

Amphotericin B↗
PubMed1992

A Pan-American 5-year study of fluconazole therapy for deep mycoses in the immunocompetent host. Pan-American Study Group.

Eighty-eight immunocompetent patients with deep mycoses from eight countries were evaluated with the same protocol for efficacy of fluconazole monotherapy. Entry doses were raised from 100 to 400 mg as safety was shown in initial cohorts, and dosages up to 2,400 mg daily and durations up to 44 months were studied. Results were very similar in different countries. Twenty-seven of 28 evaluable patients with paracoccidioidomycosis, 13 of 19 with sporotrichosis, 14 of 16 with coccidioidomycosis, and eight of eight with histoplasmosis demonstrated objective responses to therapy, as did one patient each with zygomycosis and alternariosis. For these patients, relapses have been unusual thus far. In contrast, one patient with chromoblastomycosis responded but relapsed, and six did not respond; one patient with mycetoma responded but relapsed, and two did not respond. The drug was well tolerated by patients, including six who received intravenous therapy. In vitro susceptibility tests suggested that clinical response was correlated with susceptibility but that resistance did not preclude clinical response. Fluconazole therapy appears efficacious for several deep mycoses; dosages of greater than 200 mg daily may be needed for some diseases. The further evaluation of fluconazole for these entities is warranted.

Adolescent↗
PubMed1991

Lymphocyte subpopulations and cytokine production in paracoccidioidomycosis patients.

Despite the postulated role of the immune system in the control of the infection by Paracoccidioides brasiliensis, only a few studies have addressed this point in patients. The determination of total lymphocytes and their subpopulations in 6 untreated patients with the chronic form of paracoccidiodomycosis showed that half of them were lymphopenic, because of low number of CD4+ T-lymphocytes. All patients had low CD4/CD8 ratios. On the contrary, B-lymphocytes were normal in all patients. An additional patient, studied on treatment with ketoconazole, had normal lymphocyte counts in all subpopulations, as did one of the patients previously studied at diagnosis when he received specific antimycotic treatment. The production of interferon and tumor necrosis factor, determined by bioassay in supernatants of mononuclear blood cells of the patients, induced by interleukin 2 in vitro was significantly lower than that of normal subjects. These results show that patients with paracoccidioidomycosis have a defect in blood lymphocyte subsets as well as in the ability to produce regulatory cytokines.

Adult↗
PubMed1991

Treatment of experimental cryptococcosis with SCH 39304 and fluconazole.

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

Animals↗
PubMed1989

Comparative study of four antifungal drugs in an experimental model of murine cryptococcosis.

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

Animals↗
PubMed1989

Treatment of disseminated histoplasmosis in hamsters.

A comparative study between itraconazole, ketoconazole and amphotericin B in the treatment of experimental histoplasmosis in hamsters was carried out. Seventy five animals were inoculated intracardiacally with the yeast-phase of Histoplasma capsulatum. They were divided in 5 groups: 1) treated with itraconazole by gavage (g) at a daily dose of 16 mg/kg; 2) treated with ketoconazole by (g) at a daily dose of 80 mg/kg; 3) treated with amphotericin B intraperitoneally (i.p.) at 6 mg/kg every other day; 4) control animals receiving distilled water i.p. and 5) control animals receiving P.E.G. 200 by (g). All the treatments were started one week after the challenge inoculation and they were given for 21 days. The results were evaluated by autopsy of all the animals one week after the end of the treatments. The following determinations were taken into account: microscopic examinations of spleen, liver and lungs and cultures of the spleen with determination of colony forming units/g. All the antifungal drugs used in this study were able to cause negative microscopic examinations of the liver, spleen and lungs; but only amphotericin B produced culture negative results. Itraconazole and ketoconazole presented 66% and 86% of positive cultures respectively, nevertheless the C.F.U. were lower than those obtained in control groups. In these experimental conditions amphotericin B seems to be more active than the azolic compounds and itraconazole is slightly superior to ketoconazole at a lower dose.

Amphotericin B↗
PubMed1989

[Evaluation of an enzyme immunoassay for the rapid diagnosis of paucibacillary tuberculosis in adults].

The ELISA has been extensively evaluated as a serodiagnostic method for tuberculosis. However, there is scarce information about its application to cases that cannot be diagnosed by microscopic examination: those with closed lesions or undergoing early stages of the disease. Since a reliable serological test might substantially contribute to their prompt detection, the objective of the present study was to determine the diagnostic value of an ELISA applied to adult smear-negative cases of tuberculosis. Sera from 235 patients with active tuberculosis--176 pulmonary and 59 extrapulmonary cases--and 181 control subjects were tested for IgG antibodies to PPD by ELISA. Eleven cases of non tuberculous mycobacterial (MOTT) disease and 33 cases of mycosis were also included in this group. With the adopted cut-off value, 73.9% (105/142) of smear positive and 52.7% (49/93) of smear negative tuberculosis cases, were correctly classified. Particularly in the latter, the test was positive in 55.2% (32/58) of patients with positive cultures for Mycobacterium tuberculosis and in 48.6% (17/35) of patients diagnosed by clinical, radiological and or histopathological findings. No antibody activity was demonstrated in 92.7% of sera from the control population which included 92 healthy volunteers, 32 non tuberculous diseased subjects and 13 household contacts of smear-positive cases. Among those control subjects who were skin tested, ELISA results were not related to the tuberculin reactivity: 93.7% (30/32) of tuberculin negative and 95.2% (40/42) of tuberculin positive healthy individuals had no detectable antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Itraconazole in human histoplasmosis.

A non-comparative open trial with itraconazole in progressive forms of human histoplasmosis was carried out. Thirty two patients who completed 6 months of treatment were included; 29 suffered the chronic disseminated form; 2 exhibited a chronic pulmonary histoplasmosis and one patient presented a subacute disseminated form. Thirty patients were males and 2 females; their ages ranged from 37 to 78 years old (average 56.9). The following underlying diseases were registered: hepatopathies: 12 cases; endocrinopathies and steroid therapy: 13 cases; chronic obstructive pulmonary disease: 10 patients; malignancies: 3 cases; long treatment with psychotropic drugs; 2 cases and 1 immunodeficiency of unknown origin. The therapeutic schedule applied was: 100 mg/day, orally, during 2 months, followed by 50 mg/day for another four months. Twenty-nine patients achieved clinical cure, two showed a striking improvement (both had the chronic pulmonary form) and the treatment could not be evaluated in 1 case. A follow-up of longer than a year was registered in 23 cases, one died as a consequence of mesothelioma and another due to renal impairment, and no relapses were observed. A decreasing complement fixation titer (of more than 2-fold) was observed in 19 cases; 8 of 10 patients with negative skin tests turned positive and the erythrocyte sedimentation rate was reduced to more than a half in 24 cases. Concerning side-effects, a mild, transient and asymptomatic rise of the hepatic enzymes was registered in 9 patients. It seems that itraconazole will be the drug of choice in the treatment of human histoplasmosis in immunocompetent patients.

Adult↗
PubMed1989

[Pharmacokinetic interaction of ketoconazole, isoniazid and rifampicin].

Eight male tuberculous patients, between 20 and 60 years of age, were given Isoniazid 5 mg/kg and Ketoconazole 200 mg, first one at a time and then associated. Plasma concentrations were measured 0, 2 and 5 hs after taking the drugs. Isoniazid was measured by spectrophotometry and Ketoconazole by the microbiologic method with Candida albicans as test microorganism. When both drugs were given simultaneously Ketoconazole plasma concentration decreased 75% at 2 hs (p less than 0.025) and 85% at 5 hs (p less than 0.05), whereas that of Isoniazid remained unchanged (Table 1). Mean half-life of Isoniazid was 3.9 +/- 1.4 hs in 7 slow acetylators and 1.1 hs in one fast acetylator when given one at a time and 4.4 +/- 1.5 hs when given simultaneously. A similar study was conducted on 11 tuberculous patients who were given Rifampicin 10 mg/kg and Ketoconazole 200 mg, one at a time and concurrently. Rifampicin was measured by high pressure liquid chromatography. When Rifampicin and Ketoconazole were given concurrently plasma concentration of both drugs was reduced: Ketoconazole decreased 85% at 2 hs (p less than 0.025) and 98% at 5 hs (p less than 0.025) whereas Rifampicin decreased 45% at 2 hs (p less than 0.005) and 40% at 5 hs (p less than 0.005) (Table 2). Mean half-life of Rifampicin was 3.5 +/- 0.8 and 4.2 +/- 1.1 hs, respectively, when it was given alone and concurrently. Studies on chemical interactions between Isoniazid and Ketoconazole and between Rifampicin and Ketoconazole yielded negative results.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗