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Biomedical subjects

Paolo Benedetti

Publications and source records attributed to Paolo Benedetti.

10 recordsLinked to original sources
PubMed2006

Association between Enterococcus bacteraemia and death in neutropenic patients with haematological malignancies.

Fatality rates and prognostic factors for mortality due to Enterococcus spp. bacteraemia have not yet been fully defined in the setting of neutropenic patients affected with haematological malignancies. We have performed a retrospective, multi-centre cohort study on 98 episodes of Enterococcus bacteraemia occurring in patients hospitalised from January 1984 to December 2001 at the oncohaematology units in two tertiary-care hospitals (Verona Hospital and Vicenza Hospital, in north-east Italy). E. faecalis was isolated in 52 cases (53%), E. faecium in 39 (39.8%), E. avium in four, E. durans in one, and untyped Enterococcus spp. in two other cases; vancomycin resistance was detected in 15 (15.3%) isolates. A global mortality rate of 41.8% (41/98 cases) was revealed; Enterococcus spp. bacteraemia was associated with a fatal outcome in 29/98 cases (29.5%). The following variables were independently associated with an increased risk of death by multivariate analysis of survival: age > or =50 years (OR 3.74; 95% CI 1.35-10.32), pneumonia (OR 4.70; 95% CI 1.67-13.20), and shock (OR 13.7; 95% CI 1.23-152.43), while the initial phase of haematological disease (responsive to chemotherapy) appeared to be protective (OR 0.23; 95% CI 0.008-0.64, P level 0.005); however, pneumonia alone (OR 7.2, 95% CI 2.52-20.88) was independently associated with fatal outcome by multivariate analysis for death related to enterococcal bacteraemia. In our experience, the poor outcome proper to enterococcal bacteraemia appears to be directly related to underlying disease, patient's age, presence of pneumonia and shock; in contrast, severe neutropaenia, antibiotic resistance, and species of Enterococcus do not appear to affect the fatality rate significantly.

Adolescent↗
PubMed2005

HPV genotype prevalence in cervical specimens with abnormal cytology: a report from north-east Italy.

We have investigated the prevalence of HPV DNA in cervical samples collected from 1335 women with abnormal Pap test and analysed the degree of association of HPV genotype with cervical cytological abnormality and also with patient age. The study was principally aimed at providing some cross-sectional figures on the epidemiology of HPV in our area, where the ethnic background is expected to rapidly evolve due to extensive immigration from overseas. 471 (35.3%) of the 1335 patients screened were positive for HPV DNA. A clear association was observed between cytological findings and the proportion of patients with positive HPV PCR, namely 24.0% HPV positivity in the ASCUS group (atypical squamous cells of undetermined significance), 48.7% in LSIL group (low grade squamous intraepithelial lesions), and 71.9% in HSIL group (high grade squamous intraepithelial lesions) (p-value < 0.001). High-risk (HR) HPV prevalence appeared to be different from other areas of the world; we have detected a high prevalence rate of HPV-16, 31, and 58 and a low prevalence rate of HPV-18 and 11. The prevalence of both HR and low risk (LR) genotype groups was clearly related to age (p-value < 0.001), since the prevalence of LR group had a nadir between 41 and 50 y of age and 2 peaks at 15-20 y and at over 60 y, while the curve of prevalence of HR genotypes displayed an almost inverse trend.

Adolescent↗
PubMed2004

GRIND/ALMOND investigations on CysLT1 receptor antagonists of the quinolinyl(bridged)aryl type.

One of the current routes in developing antiasthmatics is CysLT(1) receptor antagonism. For a training set of 54 CysLT(1) receptor antagonists of the quinolinyl(bridged)aryl type we developed chemometric QSAR models applying GRID independent descriptors (=GRIND). PLS analysis resulted in a two-component model explaining 67% of the variance for CysLT(1) receptor binding (r2=0.67, SDEC = 0.47, q2=0.54). GRIND variables 11-50 and 22-55 are responsible for high-affinity binding; variable 11-62 is detrimental. The predictivity of the above chemometric model is tested with a set of 69 CysLT(1) receptor antagonists, exhibiting varying chemical similarity to the training set. Nearly 50% of the test set are quite well predicted. The quality of prediction coincides in part with chemical subclassification: phenylene bridged compounds are quite well predicted; for structures with bridging heterocycles predictions are rather poor. For explaining the outlier behavior, a PLS discriminant analysis including the training set and the strongest outliers of the test set was performed. The scores plot of discriminant PLS shows an almost complete separation between the two subsets. A PLS coefficients plot explains which GRIND variables are important for the discrimination between the training set and the outliers of the test set.

Asthma↗
PubMed2004

Design, synthesis and in vitro antitumor activity of new trans 2-[2-(heteroaryl)vinyl]-1,3-dimethylimidazolium iodides.

The design, the synthesis, and the in vitro antitumor activities of trans 2-[2-(heteroaryl)vinyl]-1,3-dimethylimidazolium iodides versus MCF7 (human mammary carcinoma) and LNCap (prostate carcinoma) cell lines are reported. The design indicates trans 2-[2-[5-(2-chlorophenyl)furan-2-yl]vinyl]-1, 3-dimethylimidazolium iodide 5 and trans 2-[2-[5-(4-bromophenyl)furan-2-yl]vinyl]-1, 3-dimethylimidazolium iodide 6 as highly active compounds in the series. The synthesis of the above new derivatives and in vitro antitumor tests, confirm their significant antiproliferative and cytotoxic activities.

Antineoplastic Agents↗
PubMed2004

Structure-based rationalization of antitumor drugs mechanism of action by a MIF approach.

Structural patterns for antitumor drugs, evidenced by means of a molecular interaction field (MIF) approach using grid independent descriptors (GRIND), resembled closely those of a previous independent pharmacological classification based on their antitumor mechanism of action. For topoisomerase II inhibitors, antimitotic agents and DNA antimetabolites, systematic structural patterns were evidenced by MIF and the structural features of "outliers" in these classes corresponded to peculiar pharmacological mechanisms of action supported by literature evidences. Alkylating agents and DNA/RNA antimetabolites, interacting with a large variety of targets by different molecular mechanisms, did not exhibit clustering in the structure-based MIF approach. Moreover MIFS were able to point out similarities between drugs which, in spite of apparent dramatic differences in chemical structure, exhibit the same pharmacological behaviour.

Antineoplastic Agents↗
PubMed2003

A randomized trial of consensus interferon in combination with ribavirin as initial treatment for chronic hepatitis C.

BACKGROUND/AIMS: The aim of the present, open-labeled, randomized study was to determine the efficacy and safety of different doses of consensus interferon plus ribavirin in the initial treatment of chronic hepatitis C. METHODS: One hundred and one genotype 2/3 patients were randomized to receive 9 mcg (group A, n=48) or 18 mcg (group B, n=53) of consensus interferon thrice weekly plus ribavirin (1000/1200 mg/daily) for 24 weeks and 92 genotype 1 patients to receive 9 mcg (group C, n=47) or 18 mcg (group D, n=45) of consensus interferon plus ribavirin for 48 weeks. RESULTS: In an intention-to-treat analysis, the sustained virologic response at 24-week follow-up was 69% and 66% for group A and B (P=0.77) and 40% and 36% for group C and D (P=0.63). The overall sustained response was 67% and 38% in patients with genotype 2/3 and 1, respectively. Among genotype 1 patients the sustained virologic response was 39% and 41% for high or low baseline viremia levels. CONCLUSIONS: Higher consensus interferon dose does not increase sustained virologic response. Naive genotype 1 patients may achieve significant response rate of approximately 40% if treated with 9 mcg of consensus interferon plus ribavirin for 48 weeks.

Adult↗
PubMed2002

GBR compounds and mepyramines as cocaine abuse therapeutics: chemometric studies on selectivity using grid independent descriptors (GRIND).

Cocaine is one of the most widely abused drugs in the industrial world. Substantial evidence has accumulated that the dopamine transporter (DAT) is a key target for cocaine regarding its reinforcing effects. This work describes the application of chemometric methods to a data set of 54 N(1)-benzhydryl-oxy-alkyl-N(4)-phenyl-alk(en)yl-piperazines (GBR compounds) and chemically related mepyramines as putative candidates in cocaine abuse therapy. The aim of the study is to gain insight into the structural requirements that determine the affinity of the data set molecules to the DAT and the serotonin transporter (SERT) as well as their inhibitory potency on dopamine uptake. The compounds in the dataset are described using the recently developed GRID independent descriptors (GRIND), which allow one to obtain fast three-dimensional quantitative structure-activity relationship models without the need of aligning and superimposing the structures; the results are interpreted in a convenient pharmacophoric-like fashion. In the first part of the work, the selectivity of the database molecules for DAT binding vs dopamine reuptake inhibition is investigated. In the second part, the selectivity of the compounds for DAT binding vs SERT binding is studied. In both cases, significant models are obtained, which define the structural features responsible for the respective selectivity profiles. Moreover, the information has potential interest for the design of new derivatives with improved selectivity.

Carrier Proteins↗
PubMed2002

Distant collaboration in drug discovery: the LINK3D project.

The work describes the development of novel software supporting synchronous distant collaboration between scientists involved in drug discovery and development projects. The program allows to visualize and share data as well as to interact in real time using standard intranets and Internet resources. Direct visualization of 2D and 3D molecular structures is supported and original tools for facilitating remote discussion have been integrated. The software is multiplatform (MS-Windows, SGI-IRIX, Linux), allowing for a seamless integration of heterogeneous working environments. The project aims to support collaboration both within and between academic and industrial institutions. Since confidentiality is very important in some scenarios, special attention has been paid to security aspects. The article presents the research carried out to gather the requirements of collaborative software in the field of drug discovery and development and describes the features of the first fully functional prototype obtained. Real-world testing activities carried out on this prototype in order to guarantee its adequacy in diverse environments are also described and discussed.

Computer Graphics↗