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Biomedical subjects

M Cassone

Publications and source records attributed to M Cassone.

8 recordsLinked to original sources

Personalizing gene therapy in gastric cancer.

Gene therapy was proposed many decades ago as a more straightforward and definitive way of curing human diseases, but only recently technical advancements and improved knowledge have allowed its active development as a broad and promising research field. After the first successes in the cure of genetic and infectious diseases, it has been actively investigated as a means to decrease the burden and suffering generated by cancer. The field of gastric cancer is witnessing an impressive flourishing of studies testing the possibilities and actual efficacy of the many different strategies employed in gene therapy, and overall results seem to be two-sided: while original ideas and innovative protocols are providing extremely interesting contributions with great potential, more advanced-phase studies concluded so far have fallen short of expectations regarding efficacy, although invariably demonstrating little or no toxicity. An overview of the major efforts in this field is provided here, and a critical discussion is presented on the single strategies undertaken and on the overall balance between potentiality and pitfalls.

Adenoviridae↗

Activity of moxifloxacin in combination with vancomycin or teicoplanin against Staphylococcus aureus isolated from device-associated infections unresponsive to glycopeptide therapy.

We tested the in vitro bactericidal activity of moxifloxacin, a new 8-methoxyquinolone, alone and in combination with vancomycin or teicoplanin at different multiples of minimum inhibitory concentration (MIC) against 8 methicillin-ciprofloxacin-resistant Staphylococcus aureus (M-C-RSA) and 1 methicillin-ciprofloxacin susceptible S. aureus (M-C-SSA) recently isolated from device-associated infections unresponsive to or relapsing after glycopeptide therapy, despite device removal. MICs of vancomycin ranged from 1 to 4 microg/ml, MICs of teicoplanin ranged from 2 to 8 microg/ml; MICs of moxifloxacin were always 2 microg/ml against M-C-RSA isolates and 0.125 microg/ml against the M-C-SSA isolate. The 9 strains resulted tolerant when tested for vancomycin, teicoplanin, and moxifloxacin used alone at 2 x MIC. In all cases the combination of moxifloxacin and teicoplanin or vancomycin appeared to be bactericidal already at MIC concentration for glycopeptides plus 0.5 x MIC concentration for moxifloxacin. If these results are confirmed in vivo in animal experiments, the combination of moxifloxacin with glycopeptides might be useful for treating device-associated infections, and in preventing the frightening phenomenon of increasing MICs for glycopeptides.

Anti-Infective Agents↗

Conservative medical therapy of infections following osteosynthesis: a retrospective analysis of a six-year experience.

The conventional therapeutic approach to bone infection associated with osteosynthesis is based on the idea that microbial eradication is most readily achieved by removal of the foreign material together with adequate antimicrobial therapy. This strategy usually requires implantation of external fixation devices with additional discomfort to the patient. We report our experience with conservative medical and antimicrobial therapy without removal of the osteosynthesis until adequate bone callus deposition is documented by bone radiography scan. Twenty patients with infections associated with intramedullary nailing (9 patients), screws and plate (9 patients) or screws (2 patients) were treated between 1995 to 2000. Osteosynthesis implantation sites were tibia (7 patients), femur (6 patients), femur and tibia (1 patient), humerus (1 patient), others (5 patients). Diagnosis of infection was based on clinical-microbiological evidence and confirmed by 99Tc-labeled leukocyte scan studies. Offending pathogens were Staphylococcus aureus 17 cases, Staphylococcus aureus + Escherichia coli, Staphylococcus epidermidis, unknown, 1 case each. Most infections were initially treated with intravenous or intramuscular teicoplanin +/- ciprofloxacin or rifampin followed by oral antimicrobial therapy usually with ciprofloxacin or minocycline plus rifampin. Mean duration of antimicrobial therapy was 27.7 weeks (range 12-64 weeks). All patients (100%) were cured, and none complained of side-effects requiring antibiotic therapy discontinuation. We conclude that conservative medical therapy is feasible for osteosynthesis-associated bone infection.

Adolescent↗

Prosthetic biologic valve endocarditis caused by a vancomycin-resistant (vanA) Enterococcus faecalis: case report.

We recently observed (February 1999) a 68-year old patient with endocarditis on a prosthetic biologic valve caused by a vancomycin-resistant Enterococcus faecalis. Broth dilution tests showed susceptibility to ampicillin (MIC=0.5 microg/ml), no high resistance to aminoglycosides (MIC for gentamicin <500 microg/ml) and resistance to vancomycin (MIC >256 microg/ml) and teicoplanin (MIC >16 microg/ml). A PCR assay detected vanA gene in this strain. A transthoracic echocardiogram did not show valvular vegetations. A possible endocarditis was diagnosed and the patient received ampicillin for 8 weeks and gentamicin for 6 weeks. The patient remained afebrile after a 4-month follow-up when he underwent surgical replacement of the dysfunctional bioprosthetic valve. Mitral valve was sterile on culture, but histology confirmed the diagnosis of previous endocarditis. This is the third case of endocarditis caused by vancomycin-resistant E. faecalis reported to date.

Aged↗

Comparative in-vitro activity of moxifloxacin, penicillin, ceftriaxone and ciprofloxacin against pneumococci isolated from meningitis.

Minimum inhibitory concentrations of penicillin, ceftriaxone, ciprofloxacin, and moxifloxacin (BAY 12-8039), a new 8-methoxyquinolone, were determined for 60 cerebrospinal fluid isolates of Streptococcus pneumoniae collected during January 1997-April 1998 at Italian medical centres. Three reference isolates with predetermined MIC values (two penicillin- and multidrug-resistant isolates, one uniformly susceptible to all antibiotics) were also tested with the same antibiotics. The MIC90 of penicillin was < or = 0.03 mg/L (range < or = 0.03-2 mg/L), of ceftriaxone 0.06 mg/L (range < or = 0.03-0.5 mg/L), of ciprofloxacin 2 mg/L (range 0.5-8 mg/L) and of moxifloxacin 0.06 mg/L (range 0.03-0.12 mg/L). Moxifloxacin was effective against all the penicillin-resistant isolates tested, with an MIC of 0.06 mg/L. Moxifloxacin was 32-fold more active than ciprofloxacin and was not affected by penicillin and cephalosporin resistance. These results indicate that moxifloxacin could be useful for the treatment of both penicillin-sensitive and -resistant S. pneumoniae meningitis.

Anti-Bacterial Agents↗

In vitro susceptibility of Staphylococcus aureus isolated from blood to currently used antistaphylococcal drugs.

Changes in antibiotic susceptibility was evaluated in 77 consecutive nosocomial clinical isolates of Staphylococcus aureus collected from 1986 to 1994 at the Umberto I Polyclinic of the University of Rome (63 isolates) and from 7 other Roman hospitals (14 isolates). Oxacillin resistance in these isolates increased from 39% during the 1980s to 69% during the 1990s. Significant increases in resistance to ciprofloxacin, clindamycin and rifampicin were observed among oxacillin-resistant strains. No resistance to glycopeptides was observed although both teicoplanin and vancomycin had slightly reduced antistaphylococcal activity.

Anti-Bacterial Agents↗

Fatal suppurative mesenteric thrombophlebitis caused by an Enterococcus faecalis highly resistant to aminoglycosides: case report.

A 56-year old man with non-Hodgkin's lymphoma and biliary tract endoprosthesis, developed chronic bacteremia caused by Enterococcus faecalis with high-level resistance to gentamicin and streptomycin. The sources of bacteremia were a device-associated biliary tract infection, a suppurative thrombophlebitis of the confluence of the superior mesenteric vein with the splenic vein as well as multiple liver and pancreatic abscesses. Despite antibiotic therapy and multiple drainages of abscesses, the patient died due to overwhelming infection.

Anti-Bacterial Agents↗

[Idiopathic CD4+ T-lymphocyte deficiency: the clinical evolution of a case].

The case of a patient with Salmonella arizonae sepsis, esophageal candidiasis, and a low CD4+ T lymphocyte count is presented. Follow-up continued for over 2 years after the patient was discharged from the hospital, and his clinical course and clinical-immunological examinations are described. After a period of several years during which the patient had recurrent acute infectious episodes, he improved markedly after cholecystectomy and toilette of the gingival inlets for severe parodontopathy. His CD4+ T cell count increased although it remained below normal values. This case points to possible hypothesis that chronic infective foci may further compromise the immune system when a congenital functional or numerical CD4+ T cell deficit is present.

Acute Disease↗