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Biomedical subjects

D Bassetti

Publications and source records attributed to D Bassetti.

At least 55 records · Page 3Linked to original sources
PubMed1996

High-dose fluconazole therapy for cryptococcal meningitis in patients with AIDS.

Fluconazole (800-1,000 mg i.v.) was administered to 14 consecutive patients with AIDS and cryptococcal meningitis. At 10 weeks the rate of clinical success was 54.5% (six of 11 patients responded to fluconazole); the Kaplan-Meier estimate of the response rate was 67.1%, and the overall mortality rate was 18.2% (two of 11 patients died). At the end of treatment, eight (72.7%) of 11 patients responded to fluconazole. The median time to the first negative cerebrospinal fluid (CSF) culture was 33.5 days (95% confidence interval, 18.3-67.3); the median time for patients with initial CSF cryptococcal antigen titers of > or = 1:1,024 was 66 days compared with 18 days for patients with initial CSF cryptococcal antigen titers of < 1:1,024 (P = .06). The median time to the first negative CSF culture for patients with an isolate for which the minimum inhibitory concentration (MIC) was 4 micrograms/mL was 56 days compared with 16 days for patients with an isolate for which the MIC was < 4 micrograms/mL (P = .11). The mean serum and CSF levels of fluconazole at steady state were 42.47 +/- 26.31 micrograms/mL and 36.63 +/- 21.08 micrograms/mL, respectively (ratio of CSF:serum, 0.86). No treatment was interrupted and no dose was tapered because of side effects. High-dose fluconazole might be an effective and well-tolerated therapeutic option for patients with AIDS and acute cryptococcal meningitis.

AIDS-Related Opportunistic Infections↗
PubMed1996

Population pharmacokinetics of dapsone administered biweekly to human immunodeficiency virus-infected patients.

The population pharmacokinetics of dapsone were examined in human immunodeficiency virus-infected patients receiving dapsone at a dosage of 100 mg twice weekly for the prevention of Pneumocystis carinii pneumonia. Nonlinear mixed-effect modeling was used to determine the best pharmacostatistical model for the data. A one-compartment open model with first-order absorption and elimination was used as the structural pharmacokinetic model. Several covariates were tested for their influence on pharmacokinetic parameters. Rifampin was found to increase the values of clearance/bioavailability (CL/F) and volume of distribution/ bioavailability (V/F) by approximately 70%. CL/F and V/F were 1.83 liters/h and 69.6 liters, respectively, for patients not taking rifampin. The effect of rifampin on the pharmacokinetic parameters of dapsone was appreciably less than expected on the basis of studies with healthy volunteers. Increased bilirubin levels were associated with a significant decrease in the absorption rate constant (Ka). However, this finding may be considered clinically irrelevant because the post hoc Bayesian estimates of Ka for patients with high bilirubin levels ( > 1.2 mg/dl) were at the lower bound of the values for patients with normal bilirubin levels. The value of Ka was 0.957 h-1 for a patient with a bilirubin level of 0.7 mg/dl. After inclusion of covariates in the model, the interpatient variability was 35% for CL/F, not significant for V/F, and 85% for Ka. Simulation of plasma concentration-versus-time curves indicated that the administration of 100 mg of dapsone biweekly is associated with sustained dapsone levels in the plasma of the majority of the patients. Dosage adjustments for patients concomitantly treated with rifampin may be necessary.

AIDS-Related Opportunistic Infections↗
PubMed1995

T cell blastogenic responses to Toxoplasma gondii trophozoites among HIV-infected patients.

OBJECTIVE: To evaluate the cell-mediated immune response to Toxoplasma gondii (T. gondii) among HIV-infected patients. METHODS: Forty HIV-infected patients were studied. Of them, 35 had antibodies to T. gondii and 5 had not. Nine of 35 patients with detectable serum Toxoplasma antibodies were classified as group A1 (CDC 1993), 10 as group B2, 6 as group B3, and 10 as group C3. Peripheral blood mononuclear cells (PBMCs) were obtained by Ficoll-Hypaque gradient centrifugation. Living Toxoplasma gondii trophozoites, herpes simplex virus (HSV), tetanus toxoid, and phytohemoagglutinin (PHA) were used in standard proliferation assays. Toxoplasma-responding blasts were expanded and assayed for antigen specificity and HLA restriction by proliferation assays. T cell subsets were analyzed using two-color flow cytometry. RESULTS: Among patients with detectable Toxoplasma serum antibodies, significant PBMC proliferation in response to T. gondii trophozoites was observed in those classified in group A1 or B2 but not in those in groups B3 and C3. Toxoplasma-induced blasts from five of six patients after 7 days of culture and from five patients after 15 days of culture proliferated in response to T. gondii in the presence of either autologous or allogeneic PBMCs as antigen-presenting cells (APCs) and/or also proliferated in response to HSV. The surface markers of T. gondii-induced blasts showed a variable percentage of CD4 and CD8 activated cells. CONCLUSIONS: T cell proliferative response to living trophozoites of T. gondii is lost only in patients with severe depletion of CD4 cells. PBMC proliferation was observed only in patients with previous T. gondii infection, but the T cell blasts generated showed a strong alloreactivity (proliferating in response to allogeneic irradiated PBMCs) and were apparently not antigen specific (proliferating also in response to HSV).

Adult↗
PubMed1995

Pentoxifylline as a supportive agent in the treatment of cerebral malaria in children.

In an open, randomized, controlled therapeutic trial, 56 children with cerebral malaria (CM) were randomly assigned to receive standard quinine regimen with or without pentoxifylline (10 mg/kg/day by continuous intravenous infusion). Pentoxifylline exerted an inhibitory effect on the synthesis of tumor necrosis factor (TNF), a possible mediator of CM. The 26 children who received pentoxifylline had significantly shorter comas than controls (median, 6 vs. 46 h; P < .001) Pentoxifylline recipients showed a trend toward a lower mortality, with a borderline significant difference (P = .055). The better outcome in the pentoxifylline group was associated with a decline in TNF serum levels on the third day of treatment in a few subjects that was not seen in controls. While alternative or concurrent mechanisms of action may be of some relevance, larger double-blind trials are needed to determine whether pentoxifylline has a therapeutic role in CM.

Adolescent↗
PubMed1995

Pharmacokinetics of dapsone in human immunodeficiency virus-infected children.

Dapsone, administered at various doses and schedules, has been proven to be a safe and effective alternative to trimethoprim-sulfamethoxazole for prevention of Pneumocystis carinii pneumonia (PCP) in adults with human immunodeficiency virus (HIV) infection. Dapsone is also recommended by the Centers for Disease Control for PCP prophylaxis in HIV-infected children. However, the suggested dosage regimen is based upon clinical experience with children with leprosy and dermatitis herpetiformis rather than pharmacokinetic and pharmacodynamic data obtained from the target patient population. In order to determine a rational dosage regimen that could be tested in clinical studies aimed at the evaluation of dapsone for the prevention of PCP in HIV-infected children, we studied the pharmacokinetics of dapsone following a 2-mg/kg of body weight oral dose in twelve HIV-positive children aged 9 months to 9 years. Plasma was collected at the following times after dapsone administration: 0, 2, 4, 6, 12, 24, 48, 72, and 96 h. The levels of dapsone in plasma were determined by high-performance liquid chromatography. Data were analyzed by noncompartmental methods. Expressed as means +/- standard deviations (ranges), the pharmacokinetic parameters were as follows: peak concentration in plasma, 1.12 +/- 0.48 (0.44 to 1.81) mg/liter; time to peak concentration in plasma, 3.8 +/- 1.3 (2 to 6) h; half-life at elimination phase, 24.2 +/- 7.1 (14.4 to 35.0) h; clearance from plasma divided by bioavailability (CL/F), 1.15 +/- 0.67 (0.37 to 2.63) ml/min/kg; and volume of distribution divided by bioavailability (V/F), 2.25 +/- 1.20 (1.00 to 4.57) liters/kg. Oral CL correlated negatively with age (r = 0.614 and P = 0.034), as did V (r = 0.631 and P = 0.028). As a consequence of the high interindividual variability in growth retardation, pharmacokinetic parameters correlated with measures of body development better than they did with age (e.g., for CL/F to height, r = 0.765 and P = 0.004, and for V/F to height, r = 0.748 and P = 0.005). Since oral CL from plasma and V were positively and highly correlated (r = 0.898 and P = 0.0001), a lower absolute F may be the cause, in part, of higher values for CL/F and V/F in smaller children. The results of this study warrant the testing of a 2-mg/kg dose of dapsone administered twice or thrice weekly to HIV-infected children. The monitoring of drug levels in plasma and dosage adjustment may be necessary for smaller children.

Aging↗
PubMed1994

The fluoroquinolones as treatment for infections caused by gram-positive bacteria.

The fluoroquinolones have become attractive options as treatment for a broad range of infections caused by Gram-negative bacteria. However, the value of these antibiotics to patients with infections caused by Gram-positive pathogens remains controversial. Experience with quinolones as therapy for skin and skin structure infections, osteomyelitis and peritonitis in patients receiving continuous ambulatory peritoneal dialysis suggests that the concerns which have been expressed about the use of these agents against methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis and streptococci are justified; indeed, the frequent emergence of quinolone-resistant strains of MRSA and coagulase-negative staphylococci either during or following treatment is now well documented. The fluoroquinolones should be prescribed with caution to patients with community-acquired pneumonia or whenever severe infection of pneumococcal aetiology is proven or suspected. As prophylaxis for the granulocytopenic patient, quinolones such as norfloxacin and ciprofloxacin have been shown to be effective in reducing the incidence of morbidity attributable to Gram-negative bacteria, but they have not significantly affected the incidence of infection caused by Gram-positive bacteria. In the treatment of febrile episodes in the neutropenic patient, ciprofloxacin, the quinolone investigated most extensively in this clinical setting, produced high cure rates only when it was combined with an antibiotic which was predictably active against Gram-positive organisms. We review here the role of currently-available fluoroquinolones (norfloxacin, enoxacin, pefloxacin, ofloxacin and ciprofloxacin) as treatment for these and other infections.

Agranulocytosis↗
PubMed1993

Pneumocystis carinii pneumonia during primary HIV-1 infection.

3 patients with severe CD4 lymphocytopenia (62-91 cells/microL) and inverted CD4/CD8 ratios (0.13-0.15) developed Pneumocystis carinii pneumonia during symptomatic, primary HIV-1 infection. Within four months of symptom onset, their CD4 counts and CD4/CD8 ratios returned to normal. Twenty-nine to forty-eight months after acquiring HIV-1 infection, they show no signs or symptoms of progression to AIDS. Pneumocystis carinii pneumonia can occur, therefore, in primary HIV-1 infection, and profound CD4 lymphocytopenia can revert to normal without antiretroviral therapy.

AIDS-Related Opportunistic Infections↗
PubMed1993

In vitro activity of a Combretum micranthum extract against herpes simplex virus types 1 and 2.

The authors demonstrate in vitro antiviral activity of a methanolic extract of Combretum micranthum leaves against HSV-1 and HSV-2. This activity is present only in the extract dissolved 7 days before the assay, but not in the freshly prepared extract, thus indicating the presence of inactive precursors which undergo spontaneous transformations into active compounds. The alkaline autooxidation of the methanolic extract promotes this rapid transformation. The precursors have been identified as condensed catechinic tannins, which, under alkaline conditions, suffer rapid cleavage, intramolecular rearrangement to catechinic acid and autooxidation. The alkaline autooxidation products of the methanolic extract of C. micranthum and those of the synthetic catechinic acid show similar I.R. and U.V. absorption curves, as well as similar anti-HSV-1 and -HSV-2 activities. EC50s of catechinic acid autooxidation products against HSV-1 and HSV-2 replication were 2 micrograms/ml and 4 micrograms/ml, respectively, when cell cultures were treated with the compound during virus infection.

Animals↗
PubMed1993

[Acute pneumonia and cell-mediated immunity in patients with HIV infection].

The aim of this retrospective study is to evaluate the correlation between T-cell immunity and pulmonary disorders in a group of Italian subjects with HIV infection. HIV-infected patients seen at the Institute of Infectious Diseases, University of Verona, were included in this study if they had a specific acute pneumonia, a CD4+ cell count and a CD4+/CD8+ ratio during the 60 days immediately before the onset of pulmonary disease. Cases receiving any antimicrobial prophylaxis were excluded. Pneumonia was recognized by usual clinical and radiologic abnormalities. The diagnostic procedure included sputum examination, bronchoscopy with bronchoalveolar lavage and transbronchial biopsy. The specimens were processed for bacterial, mycobacterial and fungal stains and cultures. Ziehl-Neelsen, periodic acid-Schiff and silver methenamine stains were performed on the transbronchial biopsy specimens in addition to usual pathologic examinations mononuclear. Determination of percentage of peripheral blood mononuclear cells bearing CD4+ and CD8+ markers was done by conventional fluorescent antibody cell-sorter analysis of the mononuclear cell population. Absolute number of CD4+ lymphocytes was determined by multiplying the total lymphocyte count by the percent of mononuclear cells bearing CD4+ marker. From October 1987 to August 1991, 61 patients, 50 males and 11 females, had 65 episodes of specific pneumonia. The average age of patients was 31.4 years (range 29-59 years). The risk factors for HIV infection included intravenous drug abuse (47 patients), homosexuality (6 patients), bisexuality (3 patients) and heterosexual contact (5 patients). Before the onset of pulmonary disorders, patients were classified in the following clinical HIV-related stages: asymptomatic state (22 episodes), ARC (22 episodes) and AIDS (21 episodes). In decreasing order of frequency diagnosis of pneumonias were PCP (29 episodes), community-acquired bacterial pneumonia (16 episodes), pulmonary tuberculosis (8 episodes), nonspecific interstitial pneumonia (4 episodes), PCP and pulmonary tuberculosis (3 episodes), cytomegalovirus pneumonia (2 episodes), and one of each episode of PCP and pulmonary cryptococcosis, pulmonary candidiasis, pulmonary Kaposi's sarcoma. The mean and the standard deviation of immunologic values regarding the four primary diagnostic groups were: PCP CD4+/CD8+ 0.50 +/- 0.42, CD4+/mm3 196 +/- 190; bacterial pneumonia CD4+/CD8+ 0.53 +/- 0.44, CD4+/mm3 247 +/- 139; pulmonary tuberculosis CD4+/CD8+ 0.62 +/- 0.38, CD4+/mm3 260 +/- 170; nonspecific interstitial pneumonia CD4+/CD8 + 0.57 +/- 0.48, CD4+/mm3 240 +/- 189. No significant statistical differences with respect to CD4+/CD8 ratios and CD4+ cell counts among these diagnostic groups were found by standard analysis of variance.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗