PubMed Health⌕ Search

Biomedical subjects

M Cruciani

Publications and source records attributed to M Cruciani.

At least 37 records · Page 2Linked to original sources

Penetration of vancomycin into human lung tissue.

Vancomycin penetration into lung tissue was evaluated in thirty patients following the administration of 1 g of vancomycin as a 1 h i.v. infusion. Mean concentrations (range) of vancomycin in lung tissue were 9.6 (6.3-12.1) mg/kg at 1h, 5.7 (4.7-7.4) mg/kg at 2 h, 4.2 (0.8-6.5) mg/kg at 3-4 h, 2.4 (1.4-4.7) mg/kg at 6 h, and 2.8 (0.9-7.8) mg/kg at 12 h after the end of infusion. Ratios of lung tissue to serum concentration ranged 0.24 to 0.41 at 1 and 12 h, respectively. One of six patients observed at 6 h, and 3 of 7 patients at 12 h did not have detectable levels of vancomycin in lung tissue. A 1 h iv infusion of a 1 g dose of vancomycin does not achieve sustained lung concentrations above the MIC for susceptible staphylococci over a dosing interval of 12 h. Therefore, a more appropriate modality of administration, such as continuous infusion, should be considered.

Aged↗

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↗

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↗

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↗

Availability of synthetic salmon calcitonin in tissue fluid after a single intravenous dose.

To obtain further information about the availability of salmon calcitonin in the biophase compartment that surrounds the receptor site, salmon calcitonin concentrations in plasma and skin blister fluid (SBF) after a single i.v. dose of 100 IU synthetic salmon calcitonin were compared in 15 healthy volunteers. Serial blood and SBF samples were collected before and up to 8 h after administration and calcitonin was determined by a specific RIA. The maximum concentration in plasma was 225 pg.ml-1 (in the first sample at 15 min), whereas in SBF the mean peak of 84 pg.ml-1 was reached after about 30 min. The distribution of salmon calcitonin into SBF, defined as the ratio of the AUCs in SBF and plasma, was 1.5. The kinetic profiles of salmon calcitonin in plasma and interstitial fluid were different. Calcitonin in plasma peaked and then levelled out, while in SBF it persisted longer than in plasma. This is the first report of the distribution of salmon calcitonin into blister fluid.

Adult↗

Stability of cefodizime in solution and compatibility with other injectable drugs.

The stability of cefodizime in five intravenous infusion fluids (0.9% sodium chloride, 5% dextrose in water, 10% dextrose in water, 5% amino acid injection, 3% polygeline) was studied at room temperature and at 4 degrees C. The compatibility of cefodizime with commonly used injectable drugs (ranitidine, metoclopramide, folinic acid, furosemide, aminophilline, methylprednisolone, betamethasone, hydrocortisone, dexamethasone, ketoprofen, noramidopyrine, acetylcysteine, digoxin, diazepam, acetylsalicylic acid, chlorpromazine, clonidine, clomipramine) was studied in 0.9% sodium chloride and 5% dextrose at room temperature. At intervals during the storage periods (up to 24 hrs at room temperature; up to 6 days at 4 degrees C) color, clarity and solution pH were examined; cefodizime content was determined by a microbiological method. Cefodizime concentrations remained greater than 90% of the initial concentrations in all infusion fluids for at least 24 hrs at room temperature and 6 days at 4 degrees C. No visual changes or appreciable changes in pH were observed for any of the solutions. Immediate clouding was observed when chlorpromazine was combined with the solution of cefodizime. A color change was observed when acetylcysteine was mixed with cefodizime. An increase in pH was noted when aminophilline was added to the solution of cefodizime. However, cefodizime concentrations remained greater than 90% of the initial concentrations of the solutions after mixture with all the tested drugs for at least 24 hrs at room temperature.(ABSTRACT TRUNCATED AT 250 WORDS)

Cefotaxime↗

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↗

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↗

Risk of reactivation of tuberculosis in the course of human immunodeficiency virus infection.

OBJECTIVES: To establish, in a longitudinal study, whether reactivation of latent tuberculous infection takes place below an identifiable immunological threshold in subjects with human immunodeficiency virus (HIV) infection. METHODS: We followed up for 2 years 44 subjects with HIV infection who had a positive intradermal reaction to tuberculin. All subjects were asymptomatic at enrollment. End points of the study were the development of active tuberculosis or the final evaluation (24 months since the beginning) for those who did not develop tuberculosis over the study period. Total lymphocyte count, CD4+ lymphocyte count and beta-2 microglobulin serum levels were measured at baseline, during the period of observation (every 3-6 months) and at the end point. Multiple Antigen Skin Testing and purified protein derivative (PPD) testing were also performed at baseline and end point, as well as in intermediate phases of the study (every 6 and 12 months respectively). RESULTS: Ten subjects (22.7%) developed tuberculosis during the study period. Both baseline and end point values of the parameters investigated differed significantly between subjects who developed tuberculosis and those who did not. Cox's model showed that total and CD4+ lymphocyte counts as well as beta-2 microglobulin levels had a prognostic value at a univariate analysis; CD4+ and beta-2 microglobulin retained statistical significance in a multivariate evaluation. CD4+ lymphocyte count was the parameter most strongly associated with the development of tuberculosis. CONCLUSIONS: Tuberculosis in this setting most often reactivates only when immune surveillance has fallen to an identifiable level. Planners of antituberculous chemoprophylactic policies should consider the downgrading tendency of immune function in these subjects in order to choose the most appropriate time to intervene in the course of HIV infection. Starting prophylaxis in HIV-infected subjects only when CD4+ cells have dropped below the value of 500/mm3 seems to be a more fruitful option than the currently adopted strategy, which recommends time-limited (12 months) administration of daily isoniazid to all PPD+ HIV-infected subjects regardless their immunological status.

Adult↗

Evaluation of intraventricular teicoplanin for the treatment of neurosurgical shunt infections.

Seven patients with staphylococcal neurosurgical shunt infections were treated with intraventricular teicoplanin. Two infants received 5 mg/d, three patients received 20 mg/d, and two patients received 20 mg every other day. Six of these patients also received intravenous antibiotics. Three patients had infections caused by methicillin-susceptible Staphylococcus epidermidis, and one patient had an infection caused by methicillin-resistant S. epidermidis. Three patients were infected with Staphylococcus aureus (one with a methicillin-resistant strain and two with methicillin-susceptible strains). The mean duration of intraventricular therapy was 16 days. Sterilization of cerebrospinal fluid (CSF) was obtained after an average of 4.4 days. All patients were cured both clinically and microbiologically. No significant adverse effects were observed in any patients. Penetration of teicoplanin into the CSF after intravenous administration was poor. However, after intraventricular administration, high and prolonged peak and trough levels of teicoplanin were detected in the CSF. Bactericidal activity of the CSF was remarkable, exceeding the 1:8 dilution in the majority of the cases. The alternate-day schedule of intraventricular administration of teicoplanin was as effective as the once-daily regimen.

Adolescent↗