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Biomedical subjects

M Venditti

Publications and source records attributed to M Venditti.

At least 37 records · Page 2Linked to original sources

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↗

Antibiotic resistance and genotypic characterization by PFGE of clinical and environmental isolates of enterococci.

Fifty-four Enterococcus faecalis and 20 Enterococcus faecium isolates from clinical and non-human sources in Rome, Italy, were characterized by antibiotic resistance and pulsed field gel electrophoresis (PFGE). Resistance to vancomycin, teicoplanin, ampicillin, and ciprofloxacin was more frequent in E. faecium than in E. faecalis, whereas high-level resistance to aminoglycoside was found primarily in E. faecalis. Multi-resistance was found primarily among clinical isolates, but was also observed among environmental isolates. Common genotypes shared among clinical and environmental isolates were observed, however, the majority of isolates occurred as unique, source-specific clones. Several PFGE types were associated with shared features in their antibiotic resistance patterns; evidences of clonal spread between and within wards were also noted. This is the first report indicating clonal relatedness between human and environmental enterococci isolated in Italy.

Anti-Bacterial Agents↗

IP videoconferencing using a quality of service public network.

Videoconferencing in the medical world has been successfully used for quite a few years. Nevertheless it has not spread significantly in daily use. Some of the problems rely on the infrastructure needed to set up a video session: one or more ISDN lines or a fast Internet connection. The first is not easily available everywhere in a building; the latter is rarely so fast to allow for a smooth operation with no quality drops. The use of Videonet, the first European commercial public Internet link with guaranteed Quality of Service (QoS), has the potential to be a breakthrough in videoconferencing. We describe this new system and its applications, with the first tests in a hospital environment. Our results show that there are still problems to be solved in order to achieve a quality comparable to ISDN.

Europe↗

[Popliteal (Baker's) cyst in a patient with tubercular arthritis. Report of a case and review of the literature].

The Baker's cyst is a distension of the bursa subtendinea and is caused by noninfectious knee effusion secondary to arthrosis, meniscal tears, trauma, rheumatoid arthritis, gout, or any other form of sinovitis, like rheumatoid arthritis. An infected popliteal cyst is much less common; tuberculous arthritis is exceptional, in fact only four cases are described in literature. Herein we describe an additional tbc case of a 51 years old men, who has been initially treated with cytostatic and corticosteroid agents, for a suspected rheumatoid arthritis. The review of the literature suggests the importance of a correct approach to the diagnosis, based on the analysis and culture of the synovial fluid, because delays latency of effective antibiotic therapy can result in permanent joint damage that invalidate the patients.

Humans↗

Bacteremia due to Stenotrophomonas maltophilia in patients with hematologic malignancies.

Predisposing factors, clinical characteristics, and antimicrobial treatment of 37 hematology patients with Stenotrophomonas maltophilia bacteremia who were seen at the department of hematology of the University La Sapienza (Rome) from 1987 to 1996 were evaluated. The results were compared with a control group of patients with Pseudomonas aeruginosa bacteremia. Profound neutropenia was more prolonged in the S. maltophilia group (P=.025), severe cellulitis occurred only in S. maltophilia-infected patients (11 [30%]; P=.0002), and the bacteremia presented as breakthrough infection in 56% of the cases due to S. maltophilia (vs. only 24% of those due to P. aeruginosa; P=.002). Acute mortality rates associated with S. maltophilia and P. aeruginosa bacteremia were 24% and 21%, respectively. In both groups, profound neutropenia and hypotension at the onset of bacteremia, duration of profound neutropenia during bacteremia, severity-of-illness score > or =4, and inappropriate antibacterial treatment were factors significantly associated with death. Most S. maltophilia isolates were resistant to aminoglycosides, beta-lactams, and ciprofloxacin. Cotrimoxazole and ticarcillin-clavulanic acid showed borderline activity. Prompt administration of in vitro-active antibiotics may improve the prognosis of S. maltophilia bacteremia, especially for immunocompromised patients, and novel drug combinations are needed for the treatment of severe infections.

Adolescent↗

Murine granulocytes control human tumor growth in SCID mice.

Severe combined immunodeficient (SCID) mice generally do not reject allogeneic or xenogeneic organ grafts and represent a unique model for investigating in vivo the behaviour of both normal and neoplastic human cells. However, cells from human primary tumors often do not grow in SCID mice. We have previously shown that the major reaction of SCID mice to the engraftment of human peripheral blood leukocytes is a massive granulocyte recruitment into the site of transplantation. In this study, we have investigated the role of murine granulocytes in the control of human tumor cell growth in SCID mice. We report here that murine granulocytes infiltrate and delimit the human tumor mass and that treatment of SCID mice with anti-murine granulocyte antibody markedly improves the growth of human tumor cell lines of different origin through suppression of the host granulocyte reaction. This finding provides a new tool for improving the human tumor take in SCID mice, thus opening new perspectives for a practical in vivo preclinical test of anti-tumor strategies. Moreover, this study, even with the limits of the known natural reaction against xenotransplants, further supports the importance of granulocytes in the control of tumor take and growth.

Animals↗

Type I consensus interferon (CIFN) gene transfer into human melanoma cells up-regulates p53 and enhances cisplatin-induced apoptosis: implications for new therapeutic strategies with IFN-alpha.

In this study, we describe the effects produced by the retroviral transduction of human type I consensus IFN (CIFN) coding sequence into the 8863 and 1B6 human melanoma cell lines, derived from a metastatic and a primary human melanoma, respectively. Melanoma cell lines producing approximately 103 IU/ml of IFN were obtained. Interestingly, cisplatin treatment of IFN-producing 8863 and 1B6 melanoma cells resulted in a three- to four-fold increase in the percentage of apoptotic cells with respect to similarly treated parental or control-transduced cell cultures. A similar effect, although less intense, was caused by cultivation of parental melanoma cells in the presence of exogenous CIFN. The increased susceptibility of the IFN-producing melanoma cell lines to cisplatin-induced apoptosis was associated with an IFN-dependent accumulation of p53, which also correlated with a decrease in Bcl-2 expression. Addition of exogenous CIFN to parental melanoma cells resulted in similar although weaker modulations of p53 and Bcl-2 expression. Cisplatin administration to nude mice bearing 3-day-old IFN-producing 8863 tumors resulted in complete tumor regression, while only a partial tumor inhibition was observed upon cisplatin treatment of mice bearing parental or control-transduced 8863 tumors. Starting the cisplatin treatment 7 days after tumor cell injection still resulted in a stronger inhibition of tumor growth in the mice bearing IFN-producing 8863 tumors as compared with parental tumor-bearing mice. A comparable therapeutic effect was obtained after repeated peritumoral administration of 103 IU of exogenous CIFN and cisplatin treatment. Interestingly, a spontaneous tumor regression was observed in nude mice injected with IFN-producing 1B6 cells, in contrast to the progressive tumor growth occurring in mice receiving a similar inoculum of the parental or control-transduced 1B6 melanoma cells. Repeated peritumoral administration of 103 IU of exogenous CIFN to mice bearing parental 1B6 tumors caused only a transient inhibition of tumor growth. These results indicate that type I IFN gene transfer is an effective approach for suppressing the tumorigenic phenotype of human melanoma cells and for increasing the efficacy of anticancer drugs. These observations, together with our previous findings showing the importance of IFN-alpha-T cell interactions in the generation of an antitumor response in mouse models, underline the interest of using type I IFN in gene therapy strategies for the treatment of human melanoma.

Animals↗

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↗

Type I consensus IFN (IFN-con1) gene transfer into KSHV/HHV-8-infected BCBL-1 cells causes inhibition of viral lytic cycle activation via induction of apoptosis and abrogates tumorigenicity in sCID mice.

In this study, we investigated the effects of human type I consensus interferon (IFN-con1) (Amgen) gene transfer into body cavity-based lymphomas (BCBL)-1 cells, which are latently infected with Kaposi's sarcoma-associated herpesvirus (KSHV) human herpesvirus-8 (HHV-8). Both the basal and 12-O-tetradecanoyl phorbol-13-acetate (TPA)-stimulated production of KSHV/HHV-8 mature virions was strongly inhibited in genetically modified IFN-producing BCBL-1 cells as compared with parental or control transduced counterparts. A similar inhibition was obtained on treatment of parental BCBL-1 cells with exogenous IFN-con1. The reduction in KSHV/HHV-8 production was associated with a decrease in the basal and TPA-stimulated intracellular amount of the linear form of the viral genome. Interestingly, 25%40% of the IFN-producing BCBL-1 cell population underwent spontaneous apoptosis in vitro. TPA treatment, which did not significantly affect the viability of the parental and control BCBL-1 cells, resulted in the apoptotic death of up to 70% of the IFN-producing cell population. Addition of exogenous IFN-con1 to parental BCBL-1 cells produced similar effects, although less intense. Injection of either parental or control-transduced BCBL-1 cells into SCID mice resulted in progressively growing tumors characterized by an unusually high level of tumor angiogenesis. In contrast, complete tumor regression was observed in all the mice injected either subcutaneously (s.c.) or intraperitoneally (i.p.) with the IFN-producing BCBL-1 cells. These results represent the first evidence that type I IFN can counteract the activation of a productive herpesvirus infection in latently infected tumor cells by the induction of apoptosis, providing an interesting link between the antiviral and antitumor activities of this cytokine. These data suggest the possible advantages of strategies of type I IFN gene transfer (with respect to the use of the exogenous cytokine) for the treatment of patients with some HHV-8-induced malignancies.

Animals↗

Antimicrobial susceptibility of invasive Streptococcus pneumoniae in Italy by agar dilution method and E test.

Few data on antimicrobial susceptibility of invasive Streptococcus pneumoniae isolated in Italy are available. Ninety-two invasive isolates from all over the country collected from January 1997 to April 1998 were tested for sensitivity to penicillin, erythromycin, ceftriaxone, chloramphenicol, tetracycline, and trimethoprim/sulfamethoxazole by the agar dilution method. Five (5.4%) strains were resistant to penicillin (one highly, four intermediately resistant), 8 (8.7%) to chloramphenicol, 27 (29.3%) to erythromycin, 17 (18.5%) to tetracycline (16 highly, one intermediately), and 21 (22.8%) to trimethoprim/sulfamethoxazole (14 highly, 7 intermediately). All strains were susceptible to ceftriaxone, although the penicillin-resistant strain had the highest minimal inhibitory concentration. (MIC) value (0.5 microg/ml); three penicillin-resistant strains were also resistant to erythromycin. Eight strains were multi-drug resistant, being also resistant to at least three antibiotics. The commercially available E test was compared with the standard agar dilution method for the determination of MIC of penicillin, erythromycin, ceftriaxone, chloramphenicol, and trimethoprim/sulfamethoxazole. E test established the same susceptibility categories for 100% of the strains tested for penicillin and ceftriaxone, 99% for chloramphenicol, 97% for erythromycin, and 74% for trimethoprim/sulfamethoxazole. According to our results, E test was simple to perform, easy to interpret, and a valid method for susceptibility testing of S. pneumoniae. Our study shows that in Italy the rate of penicillin resistance in invasive isolates of S. pneumoniae is one of the lowest in Europe (5.4%), while the rate of erythromycin is very high (29.3%) and is reaching the highest rates of other Southern European countries.

Anti-Bacterial Agents↗

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↗

Importance of cyclophosphamide-induced bystander effect on T cells for a successful tumor eradication in response to adoptive immunotherapy in mice.

Cyclophosphamide (CTX) increases the antitumor effectiveness of adoptive immunotherapy in mice, and combined immunotherapy regimens are now used in some clinical trials. However, the mechanisms underlying the synergistic antitumor responses are still unclear. The purpose of this study was (a) to evaluate the antitumor response to CTX and adoptive immunotherapy in mice bearing four different syngeneic tumors (two responsive in vivo to CTX and two resistant); and (b) to define the mechanism(s) of the CTX-immunotherapy synergism. Tumor-bearing DBA/2 mice were treated with a single injection of CTX followed by an intravenous infusion of tumor-immune spleen cells. In all the four tumor models, a single CTX injection resulted in an impressive antitumor response to the subsequent injection of spleen cells from mice immunized with homologous tumor cells independently of the in vivo response to CTX alone. Detailed analysis of the antitumor mechanisms in mice transplanted with metastatic Friend leukemia cells revealed that (a) the effectiveness of this combined therapy was dependent neither on the CTX-induced reduction of tumor burden nor on CTX-induced inhibition of some putative tumor-induced suppressor cells; (b) the CTX/immune cells' regimen strongly protected the mice from subsequent injection of FLC, provided the animals were also preinoculated with inactivated homologous tumor together with the immune spleen cells; (c) CD4(+) T immune lymphocytes were the major cell type responsible for the antitumor activity; (d) the combined therapy was ineffective in mice treated with antiasialo-GM1 or anti-IFN-alpha/beta antibodies; (e) spleen and/ or bone marrow cells from CTX-treated mice produced soluble factors that assisted in proliferation of the spleen cells. Altogether, these results indicate that CTX acts via bystander effects, possibly through production of T cell growth factors occurring during the rebound events after drug administration, which may sustain the proliferation, survival, and activity of the transferred immune T lymphocytes. Thus, our findings indicate the need for reappraisal of the mechanisms underlying the synergistic effects of CTX and adoptive immunotherapy, and may provide new insights into the definition of new and more effective strategies with chemotherapy and adoptive immunotherapy for cancer patients.

Animals↗

Role of cytokines in GVL (ESb lymphoma) and GVHD after adoptive transfer of allogeneic T lymphocytes in mice.

ESb lymphoma cells injected i.v. into DBA/2 (H-2d) mice multiply rapidly in the liver and kill all mice in a few days. Adoptive transfer of allogeneic C57B1/6 (H-2b) tumor-immune or normal splenic lymphocytes to sublethally irradiated DBA/2 mice induced a marked antitumor state, graft-versus-leukemia (GVL), increasing the mean survival time 2-3-fold, but also induced an acute and lethal graft-versus host disease (GVHD). We have undertaken experiments to try to dissociate GVL from GVHD. Transfer of immune spleen cells induced a greater GVL than transfer of normal spleen cells with an equivalent to GVHD. Three to five million immune or normal CD8+ T lymphocytes were sufficient to induce both GVL and GVHD. Individual DBA/2 mice were labeled and followed. In mice undergoing GVHD, the spleens were repopulated by donor (H-2b) lymphocytes, and tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were present in the sera of 26 of 27 and 18 of 20 mice, respectively, together with increased amounts of TNF-alpha and IL-6 mRNA in their spleens. This was in contrast to DBA/2 mice receiving allogeneic cells but not developing GVHD. Both interferon-alpha/beta (IFN-alpha/beta) and IL-12, which had proven very effective in association with adoptive transfer of syngeneic immune T lymphocytes in inhibiting ESb metastases, enhanced GVHD when administered with allogeneic immune or normal spleen cells, and >90% of mice died. Intensive IL-2 treatment inhibited GVHD while maintaining GVL.

Adoptive Transfer↗

Spread of the multiresistant Iberian clone of methicillin-resistant Staphylococcus aureus (MRSA) to Italy and Scotland.

The multidrug-resistant "Iberian" clone of methicillin-resistant Staphylococcus aureus (MRSA) was first identified on the basis of its unique DNA fingerprints as the strain responsible for the massive 1989 outbreak of MRSA disease in the hospital Princeps d'Espanya, Barcelona, Spain. Most Iberian MRSA carry a constitutive beta-lactamase. They are resistant to most beta-lactam antibiotics, macrolides, aminoglycosides, tetracycline, rifampin and ciprofloxacin and are susceptible to fosfomycin, fusidic acid, mupirocin, sulfamethoxazole/trimethoprim and vancomycin. The characteristic DNA fingerprints of the clone include the mecA polymorph I, Tn554 pattern E (or its variants), a chromosomal macrorestriction pattern (pulsed-field gel electrophoretic type) A (or its subtype variants), the lack of the mecI regulatory gene and a homogeneous, high level of expression of methicillin resistance. Molecular surveillance studies have documented the extensive spread of this clone to many Portuguese hospitals during the 1990s. In this article, we describe the spread of the Iberian MRSA to hospitals in Rome, Italy, and Scotland.

Anti-Bacterial Agents↗