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Biomedical subjects

M Bassetti

Publications and source records attributed to M Bassetti.

At least 37 records · Page 2Linked to original sources
PubMed2000

Impact of an antimicrobial formulary and restriction policy in the largest hospital in Italy.

We have analysed the expenditure on antimicrobial drugs in the largest hospital in Italy; over this period, a committee prepared an antibiotic policy document. This formulary lists all antimicrobial drugs available in the hospital. Some drugs were removed from the list and others are only available on special request for a named patient. In the hope of optimising drug utilisation, we included all the reasons for the choice of agent in the document. The introduction of this formulary resulted in an immediate saving and perhaps in the future we shall also observe an improvement in bacterial resistance patterns.

Anti-Bacterial Agents↗
PubMed2000

Does HGV-HIV co-infection exist?

Hepatitis G virus (HGV) is a recently discovered virus belonging to the Flaviviridae family. Prevalence of HGV active infection (presence of HGV-RNA) in HIV-1-infected patients has been reported in various categories of patients. Our study aimed to find out its prevalence in our cohort of HIV-1-infected children. No investigated child presented with signs of HGV active infection notwithstanding the presence of many risk factors for HGV infection. Prevalence of HGV active infection in our cohort was <2.7%.

Adolescent↗
PubMed2000

Use of antibiotics in an Italian children's hospital, 1993-1995; clinical and economic considerations.

Antibiotic consumption and expenditure was studied during 1993 and 1995 in G. Gaslini children's hospital, an Italian 400-bed paediatric hospital, to see if any changes in use had occurred. There was an increase in the cost of antibacterial agents from 1993 to 1995, with a decrease in the daily cost of antibiotics and in the consumption of antiviral, antifungal and antiparasitic agents. There was a notable increase in the use of glycopeptides and carbapenems between 1995 and 1993 especially in specialities such as onco-haematology and intensive care. We suggest a basis for an antibiotic management programme aimed at reducing costs while still providing a high standard of care for patients.

Anti-Bacterial Agents↗
PubMed2000

Amphiphysin IIm, a novel amphiphysin II isoform, is required for macrophage phagocytosis.

Phagocytosis of pathogens by macrophages initiates the innate immune response, which in turn orchestrates the adaptive immune response. Amphiphysin II participates in receptor-mediated endocytosis, in part, by recruiting the GTPase dynamin to the nascent endosome. We demonstrate here that a novel isoform of amphiphysin II associates with early phagosomes in macrophages. We have ablated the dynamin-binding site of this protein and shown that this mutant form of amphiphysin II inhibits phagocytosis at the stage of membrane extension around the bound particles. We define a signaling cascade in which PI3K is required to recruit amphiphysin II to the phagosome, and amphiphysin II in turn recruits dynamin. Thus, amphiphysin II facilitates a critical initial step in host response to infection.

Amino Acid Sequence↗
PubMed2000

Possible malignant transformation of benign lymphoepithelial parotid lesions in human immunodeficiency virus-infected patients: report of three cases.

Benign lymphoepithelial parotid lesions (BLL) are intraparotid pathological changes that are commonly thought to be an early manifestation of human immunodeficiency virus (HIV) infection. It is not well known whether BLL may undergo malignant transformation into B cell lymphoma and may therefore be a sort of precancerous lesion. We report 3 cases of possible malignant transformation of BLL in HIV-infected patients.

Adult↗
PubMed2000

Indinavir pharmacokinetics and parmacodynamics in children with human immunodeficiency virus infection.

The indinavir dosage regimen currently used for human immunodeficiency virus (HIV)-infected children is not based on pharmacokinetic data obtained in the target patient population. The purpose of our study was to characterize indinavir pharmacokinetics and pharmacodynamics in HIV-infected children. Eleven children (age range, 9.0 to 13.6 years; weight range, 21.7 to 56.0 kg) receiving indinavir (500 mg/m(2) every 8 h) in combination with lamivudine and stavudine were studied. The correlation of indinavir pharmacokinetic parameters and demographic parameters was evaluated. Also, the pharmacodynamic relationship between parameters of indinavir exposure and parameters of renal toxicity and immunologic recovery was studied. The area under the indinavir concentration-time curve (AUC) and patient body surface area (BSA) showed a significant negative correlation (r = 0.73; P = 0.012). Patients with smaller BSA had excessive indinavir AUC compared to adults. On the other hand, the median minimum drug concentration in plasma (C(min)) was lower than that reported for adults. The maximum indinavir concentration in serum was higher in patients with renal toxicity (5 out of 11 children), but the difference was not statistically significant (15.3 +/- 8.2 versus 9.8 +/- 4.4 mg/liter; P = 0.19). There was a trend toward higher immunologic efficacy in patients with greater indinavir exposure: the time-averaged AUC of the percentage of CD4(+) lymphocytes over the baseline value for patients with indinavir C(min) > 95% inhibitory concentration (IC(95)) was higher than in patients with C(min) < IC(95) (P = 0. 068). Our study suggests that a dose reduction may be appropriate for children with small BSA and that a 6-h dosage regimen may be indicated for a substantial percentage of patients. Due to the low number of patients enrolled in this study, our results should be confirmed by a larger study.

Adolescent↗
PubMed1999

Dynamic interactions of macrophages with T cells during antigen presentation.

We have established a method for real-time video analysis of the interaction of antigen-presenting cells (APCs) with T cells. Green fluorescent protein expression controlled by a nuclear factor of activated T cells (NFAT)-responsive promoter permits the visualization of productive antigen presentation in single T cells. The readout is rapid (within 2 h) and semiquantitative and allows analysis by video microscopy and flow cytometry. Using this approach, we demonstrate that macrophages have the capacity to simultaneously activate multiple T cells. In addition, the interaction of T cells with macrophages is extraordinarily dynamic: after initial stable contact, the T cells migrate continuously on the surface of the macrophage and from APC to APC during productive antigen presentation. Thus, T cells sum up signals from multiple interactions with macrophages during stimulation.

Animals↗
PubMed1999

The relationship between ritonavir plasma levels and side-effects: implications for therapeutic drug monitoring.

OBJECTIVES: To assess whether the neurological or gastrointestinal adverse effects of ritonavir correlate with parameters of ritonavir systemic exposure. METHODS: Peak (Cmax) and trough (Cmin) ritonavir plasma levels were compared in 11 patients experiencing side-effects (group A) versus 10 patients without side-effects (group B). Ritonavir was administered with the following escalation dosing scheme: 300, 400, 500 mg twice a day for 3, 4, and 5 days, respectively, then the full dose of 600 mg twice a day. Blood sampling was done in group A within 24 h of the occurrence of side-effects and in group B after at least 3 days of the full dosage regimen. RESULTS: Both Cmax and Cmax were significantly higher (Mann-Whitney U test) in patients with side-effects. Cmax was [median (interquartile range)] 26.7 (22.7-33.3) mg/l versus 16.2 (13.4-17.0) mg/l (P = 0.001) and Cmin was 12.6 (9.1-13.9) versus 7.5 (4.9-8.6) mg/l (P = 0.002). CONCLUSION: Patients with higher ritonavir concentrations are at a higher risk of experiencing neurological or gastrointestinal side-effects. Individualization of the dosage regimen, e.g. a downward titration of the ritonavir dose in patients with side-effects, guided by plasma level monitoring, may result in a substantial increase in the percentage of patients tolerating ritonavir without increasing the risk of treatment failure as a result of suboptimal systemic exposure.

Adult↗
PubMed1999

The Toll-like receptor 2 is recruited to macrophage phagosomes and discriminates between pathogens.

Macrophages orchestrate innate immunity by phagocytosing pathogens and coordinating inflammatory responses. Effective defence requires the host to discriminate between different pathogens. The specificity of innate immune recognition in Drosophila is mediated by the Toll family of receptors; Toll mediates anti-fungal responses, whereas 18-wheeler mediates anti-bacterial defence. A large number of Toll homologues have been identified in mammals, and Toll-like receptor 4 is critical in responses to Gram-negative bacteria. Here we show that Toll-like receptor 2 is recruited specifically to macrophage phagosomes containing yeast, and that a point mutation in the receptor abrogates inflammatory responses to yeast and Gram-positive bacteria, but not to Gram-negative bacteria. Thus, during the phagocytosis of pathogens, two classes of innate immune receptors cooperate to mediate host defence: phagocytic receptors, such as the mannose receptor, signal particle internalization, and the Toll-like receptors sample the contents of the vacuole and trigger an inflammatory response appropriate to defence against the specific organism.

Adaptor Proteins, Signal Transducing↗
PubMed1999

A regulated secretory pathway in cultured hippocampal astrocytes.

Glial cells have been reported to express molecules originally discovered in neuronal and neuroendocrine cells, such as neuropeptides, neuropeptide processing enzymes, and ionic channels. To verify whether astrocytes may have regulated secretory vesicles, the primary cultures prepared from hippocampi of embryonic and neonatal rats were used to investigate the subcellular localization and secretory pathway followed by secretogranin II, a well known marker for dense-core granules. By indirect immunofluorescence, SgII was detected in a large number of cultured hippocampal astrocytes. Immunoreactivity for the granin was detected in the Golgi complex and in a population of dense-core vesicles stored in the cells. Subcellular fractionation experiments revealed that SgII was stored in a vesicle population with a density identical to that of the dense-core secretory granules present in rat pheochromocytoma cells. In line with these data, biochemical results indicated that 40-50% of secretogranin II synthesized during 18-h labeling was retained intracellularly over a 4-h chase period and released after treatment with different secretagogues. The most effective stimulus appeared to be phorbol ester in combination with ionomycin in the presence of extracellular Ca(2+), a treatment that was found to produce a large and sustained increase in intracellular calcium [Ca(2+)](i) transients. Our findings indicate that a regulated secretory pathway characterized by (i) the expression and stimulated exocytosis of a typical marker for regulated secretory granules, (ii) the presence of dense-core vesicles, and (iii) the ability to undergo [Ca(2+)](i) increase upon specific stimuli is present in cultured hippocampal astrocytes.

Animals↗
PubMed1999

Pharmacokinetics of rifabutin in HIV-infected patients with or without wasting syndrome.

AIMS: The purpose of the study was to compare the pharmacokinetic parameters of rifabutin obtained in a group of patients without wasting syndrome (NWS) with those obtained in a group with wasting syndrome (WS). METHODS: A single dose of 300 mg rifabutin was administered in the fasting state to the patients in both study groups and blood samples were scheduled to be collected at the following times: 0 (predose), 0.5, 1, 2, 3, 4, 6, 8, 24, 48, 72 and 96 h following administration. Data were analysed using noncompartmental methods. The pharmacokinetic parameters of rifabutin in patients with and without wasting syndrome were compared using the Mann-Whitney U-test. RESULTS: Cmax was 0.34+/-0. 14 mg l-1 in NWS patients and 0.55+/-0.16 mg l-1 (P=0.01) in patients with WS. tmax was 4.2+/-1.5 and 3.3+/-2.3 h (P=0.17) in NWS and WS patients, respectively. The AUCs were similar in the two study groups. V/F was 2905+/-1646 l in NWS patients and 1701+/-492 l (P=0.07) for the WS group. These differences are less pronounced following normalization of V/F to patients body weight (43.7+/-20.1 vs 35.4+/-10.3 l kg-1 ). t1/2,lambdaz tended to be shorter in patients with WS (31.4+/-12.9 vs 46.0+/-23.5 h, P=0.12). CONCLUSIONS: Our study suggests that the pharmacokinetics of rifabutin in patients with wasting syndrome are not altered to a degree that is clinically important.

Adult↗
PubMed1998

Penetration of clindamycin and its metabolite N-demethylclindamycin into cerebrospinal fluid following intravenous infusion of clindamycin phosphate in patients with AIDS.

Clindamycin, which is usually used in combination with pyrimethamine, has been proven effective in the treatment of cerebral toxoplasmosis in human immunodeficiency virus-infected patients. However, it is not known if clindamycin achieves inhibitory concentrations at the site of infection. Also, it has been hypothesized that the activity of clindamycin against Toxoplasma gondii may be due, at least in part, to a metabolite. We evaluated the penetration of clindamycin and its major metabolite, N-demethylclindamycin (NDC), into cerebrospinal fluid (CSF) of AIDS patients undergoing lumbar puncture for diagnostic purposes. A single, 1,200-mg dose of clindamycin was administered as a 45-min intravenous infusion beginning at 1.5 or 2.5 h before CSF sampling. The concentrations of clindamycin in CSF ranged from 0.091 to 0.429 mg/liter at 1.5 h and from 0.120 to 0.283 mg/liter at 2.5 h following the beginning of the infusion. The concentrations of clindamycin in CSF were well above the 50% inhibitory concentration of 0.001 mg/liter and the parasiticidal concentration of 0.006 mg/liter. NDC was undetectable both in plasma and in CSF. Our study provides a pharmacokinetic rationale for the clinical efficacy of clindamycin in the treatment of cerebral toxoplasmosis.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Population pharmacokinetics of rifabutin in human immunodeficiency virus-infected patients.

Rifabutin pharmacokinetics were studied by the population approach (NONMEM) with 40 human immunodeficiency virus-infected patients receiving rifabutin at different doses for prophylaxis or therapy of mycobacterial infections. A two-compartment open model with first-order absorption was used as the structural pharmacokinetic model. Parameter estimates were the absorption rate constant (0. 201/h), clearance/bioavailability (CL/F; 60.9 liters/h), volume of the central compartment/bioavailability (231 liters), intercompartmental clearance (60.3 liters/h), and volume of the peripheral compartment/bioavailability (Vp/F; 1,050 liters). The distribution and elimination half-lives were 1.24 and 25.4 h, respectively. The covariates tested for influence on CL/F and Vp/F were sex, age, weight, height, body surface area, tobacco smoking, drug addiction, alanine aminotransferase levels, creatinine clearance, total protein, bilirubin, numbers of CD4(+) cells, presence of diarrhea, cachexia index, rifabutin use (prophylaxis versus therapy), rifabutin dose, study site, and the concomitant administration of clarithromycin, fluconazole, phenobarbital, ciprofloxacin, azithromycin, or benzodiazepines. The only statistically significant effects on rifabutin pharmacokinetic parameters were a 27% decrease in Vp/F due to the concomitant administration of azithromycin and a 39% increase in Vp/F due to tobacco smoking. Such effects may be considered clinically unimportant. Our results confirm the lack of a correlation of rifabutin pharmacokinetic parameters with parameters of disease progression and gastrointestinal function. Also, the lack of a correlation with covariates which were previously found to be significant, such as concomitant fluconazole and clarithromycin use, may suggest that the effect of such covariates may be less important in the real clinical setting, in which several concomitant factors may influence pharmacokinetic parameters, with an overall effect of no apparent correlation.

Adult↗
PubMed1997

Immunodetection of glycoprotein hormone subunits in nonfunctioning and glycoprotein hormone-secreting pituitary adenomas.

While it is established that nonfunctioning pituitary adenomas (NFPA) produce a spectrum of glycoprotein hormones, the ability of glycoprotein hormone-secreting adenomas to synthesize hormones other than those in vivo hypersecreted has been poorly investigated so far. In this study the immunolocalization of the beta-subunits of LH, FSH, CG and TSH and the common alpha-subunit was investigated in 10 NFPA, 3 gonadotropin-secreting adenomas (Gn-omas, 1 LH-oma, 1 FSH-oma and 1 LH/FSH-oma) and 3 TSH-secreting adenomas (TSH-omas) using an immunohistochemical technique with specific antibodies to glycoprotein subunits. The percentage of positive cells was determined observing at least 5 photograph fields containing about 50 cells. Nine of the 10 NFPA were positive for FSH beta with a high percent of positive cells (> or =30%), 6 for LH beta and 5 for TSH beta with a lower number of labelled cells (from 5 to 30%). Of the 8 NFPA tested, 5 showed a marked positivity for CG beta. In Gn-omas, tumors were positive for the gonadotropin that was in vivo hypersecreted (10-60% positive cells) and negative for either TSH beta or CG beta. Similarly, in TSH-omas TSH beta was detected in a variable proportion of cells (10-30%) with no immunoreactivity for either LH beta or FSH beta or CG beta. This study indicates that the coexpression of FSH beta, LH beta, CG beta and TSH beta molecules is characteristic of NFPA since Gn-omas were negative for CG beta and TSH beta and TSH-omas were negative for FSH beta, LH beta and CG beta. Moreover, the biological events that make NFPA 'silent' glycoprotein hormone-secreting adenomas remain unclear since the positivity for gonadotropins and TSH showed by NFPA was similar to that observed in Gn-omas and TSH-omas, respectively.

Adenoma↗
PubMed1997

Penetration of dapsone into cerebrospinal fluid of patients with AIDS.

It has been proposed that dapsone in combination with pyrimethamine could be used for prophylaxis of both Pneumocystis carinii pneumonia and encephalitis due to Toxoplasma gondii. Ten patients with AIDS undergoing lumbar puncture for diagnostic purposes were studied in order to assess the penetration of dapsone into CSF. Blood and CSF samples were obtained between 3 and 72 h following administration. Six patients had received oral dapsone for at least 1 month at the dosage regimen of 100 mg twice of three times weekly and four patients had received a single oral 100 mg dose. Dapsone concentration in CSF ranged from 0.013 to 0.296 mg/L while concentrations in plasma ranged from 0.018 to 1.231 mg/L. The CSF:plasma concentration ratio ranged from 0.21 to 2.01. The MIC of dapsone in combination with pyrimethamine against T. gondii is unknown, and further data are required to confirm whether the CSF concentrations of dapsone found in our study are sufficient to inhibit T. gondii growth in patients infected with human immunodeficiency virus (HIV). The high interpatient variability of dapsone CSF concentrations warrants further studies in selected categories of patients with HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Immunodetection of G proteins in human pituitary adenomas: evidence for a low expression of proteins of the Gi subfamily.

G proteins mediate signal transduction in a variety of cell systems. As the expression of these proteins has not yet been investigated in detail in human pituitary tumors, we evaluated the presence of G proteins in a series of tumors including six non-functioning adenomas, five GH-secreting adenomas, three prolactinomas and one TSH-secreting adenoma, using immunoblotting and immunohistochemistry. By immunoblotting, Gi1/2alpha was undetectable in six and barely detectable in nine tumors. A similar pattern of expression was observed by probing with the antibody to Gi3alpha, which detected a very weak band in 11 tumors and no protein in four. In contrast, using large amounts of membrane proteins (40 microg), both Gi1/2alpha and Gi3alpha were detected, although at very low levels, in the negative tumors. The low expression of these proteins appeared to be specific to tumoral tissues, as both Gi1/2alpha and Gi3alpha were abundant in normal human and rat pituitary. In all tumors, Go alpha, the two Gs alpha forms, Gq/11 and G beta were present in significant amounts. Semiquantitative analysis indicated that Gs alpha was clearly detected when 2.5 microg loaded proteins were used, whereas Gi1/2alpha and Gi3alpha were barely detected with 5 microg. By immunofluorescence, all tumors studied were markedly positive for Gs alpha that was immunolocalized at the cell periphery, whereas they showed a weak positivity for Gi1/2alpha and Gi3alpha. The study is the first to provide evidence for a low expression of Gi proteins, which are involved in the transduction of inhibitory signals, in pituitary adenomas.

Adenoma↗