[Prevention of nosocomial infections: surveillance based on microbiological data]. / Effetti del monitoraggio sistematico sulla prevenzione delle infezioni ospedaliere: la sorveglianza basata sui dati del laboratorio di microbiologia.

BACKGROUND: In the C. Poma Hospital of Mantua we have been using a system of continuous surveillance of nosocomial infections based on microbiological data for the past 4 years. This monitoring estimates the incidence of the microorganisms found in cultures, especially those at risk of causing nosocomial infections. MATERIALS AND METHODS: Since June 2001 microbiological data have been registered using the Mercurio-Dianoema software and elaborated by means of Microsoft Excel in order to obtain information about isolated bacteria, especially those resistant to antibiotics. RESULTS: Surveillance in "critical" wards revealed the presence of Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans in the intensive care unit in the period 2003-2005. The most frequent bacteria in hemodialysis have been coagulase-negative Staphylococci and Staphylococcus aureus, with variable methicillin resistance. CONCLUSION: The analysis of microbiological data has promoted effective measures to reduce the incidence of these bacteria (increased rules of good practice, hand washing, etc.). If nosocomial infections or high-risk microorganisms occur, assessments are carried out; monitoring of the antibiotic resistance of the bacteria is very important.

Correlation between fine-needle aspiration cytology and histopathology in the evaluation of cutaneous and subcutaneous masses from dogs and cats.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is commonly used as a diagnostic procedure to evaluate superficial and deep masses in animals. However, few studies have addressed the accuracy of FNAC in the evaluation of cutaneous and subcutaneous masses in a clinical setting. OBJECTIVE: The purpose of this study was to compare the accuracy of FNAC as compared with histopathology in the diagnosis of cutaneous and subcutaneous masses from dogs and cats. METHODS: Cytologic and histopathologic specimens obtained between 1999 and 2003 from 292 palpable cutaneous and subcutaneous masses obtained from 242 dogs and 50 cats were retrospectively evaluated. Cytologic samples were obtained by FNA and histopathologic samples were collected by surgical biopsy or at necropsy. Concordance was determined and the accuracy of FNAC for the diagnosis of neoplasia was determined using histopathology as the gold standard. RESULTS: Of 292 specimens, 49 (from 44 dogs and 5 cats) were excluded due to poor cellularity of the cytologic specimen (retrieval rate 83.2%, n = 243). A cytologic diagnosis of neoplasia was obtained in 176 cases (175 true positives and 1 false positive compared with histopathology). Sixty-seven cytology samples were classified as non-neoplastic (46 true negatives, 21 false negatives compared with histopathology). Overall, the cytologic diagnosis was in agreement with the histopathologic diagnosis in 90.9% (221/243) of cases. For diagnosing neoplasia, cytology had a sensitivity of 89.3%, a specificity of 97.9%, a positive predictive value of 99.4%, and a negative predictive value of 68.7%. CONCLUSIONS: The results of this study confirmed FNAC as a reliable and useful diagnostic procedure for the evaluation of palpable cutaneous and subcutaneous lesions in small animal practice.

[Epidemiologic surveillance of multi-drug resistant Pseudomonas aeruginosa in Mantova Hospital (Italy)]. / Sorveglianza epidemiologica di Pseudomonas aeruginosa multiresistente nell'Ospedale di Mantova.

For the period 2002-2005 we verified and compared the data of the prevalence and resistance of Pseudomonas aeruginosa (PA) isolated in Mantova Hospital (Italy) with the data from the international database. From the first six-month period of 2004 a significant increase was found (9% vs 28.8%) in the prevalence of multi-drug resistant PA (MDR-PA). The principal wards involved were the Intensive Care Unit and the Department of Respiratory Diseases. A significant increase in resistance rates was observed for all antimicrobials tested, in particular for aztreonam, ceftazidime, ciprofloxacin, gentamycin and imipenem. The lowest dual resistance rates were observed between amikacina with piperacillin/tazobactam, while the highest were for those that included ciprofloxacin and beta-lactams (aztreonam, cefepime). In this study we confirm the importance of continuous surveillance of laboratory data and tightening local control measures for nosocomial infections in order to prevent the spread and selection of MDR-PA.

Liposome-delivered angiostatin strongly inhibits tumor growth and metastatization in a transgenic model of spontaneous breast cancer.

The possibility to inhibit tumor growth by interfering with the formation of new vessels, which most neoplasias depend on, has recently raised considerable interest. An angiogenic switch, in which proliferating cells acquire the ability to direct new vessel formation, is thought to be an early step in the natural history of solid tumors. Using a transgenic model of breast cancer, which shows many similarities to its human counterpart, including ability to metastasize, we targeted angiostatin production to an early stage of tumor formation. Liposome-delivered angiostatin considerably delayed primary tumor growth and, more importantly, inhibited the appearance of lung metastases. These findings can be relevant to the design of therapeutic intervention in humans.

p73 Overexpression increases VEGF and reduces thrombospondin-1 production: implications for tumor angiogenesis.

Tumor neovascularization is controlled by a balance between positive and negative effectors, whose production can be regulated by oncogenes and tumor suppressor genes. The aim of this study was to investigate whether the angiogenic potential of tumors could also be controlled by p73, a gene homologous to the tumor suppressor p53, whose involvement in tumor angiogenesis is known. We have studied the production of proangiogenic (VEGF, FGF-2, PIGF and PDGF) and antiangiogenic (TSP-1) factors in two p73 overexpressing clones obtained from the human ovarian carcinoma cells A2780. TSP-1 was downregulated in both clones compared to mock transfected cells, both at mRNA and protein level. Conversely, both clones showed an increased production of VEGF mRNA and protein. For both TSP-1 and VEGF, regulation of expression was partially due to modulation of the promoter activity, and was dependent on p53 status. Production of the other angiogenic factors FGF-2, PIGF and PDGF-B was also increased in p73 overexpressing clones. The two clones were more angiogenic than parental cells, as shown in vitro by their increased chemotactic activity for endothelial cells, and in vivo by the generation of more vascularized tumors. These findings suggest a potential role of p73 in tumor angiogenesis.

BAY 12-9566, a novel inhibitor of matrix metalloproteinases with antiangiogenic activity.

Matrix metalloproteinases (MMPs) have been implicated in tumor cell invasion, metastasis, and angiogenesis. BAY 12-9566, a novel, non-peptidic biphenyl MMP inhibitor, has shown preclinical activity on a broad range of tumor models and is currently in clinical development. The purpose of this study was to investigate the antiangiogenic activity of BAY 12-9566. In vitro, BAY 12-9566 prevented matrix invasion by endothelial cells in a concentration-dependent manner (IC50 = 8.4x10(-7) M), without affecting cell proliferation. In vivo, oral daily administration of BAY 12-9566 (50-200 mg/kg) inhibited angiogenesis induced by basic fibroblast growth factor in the Matrigel plug assay, reducing the hemoglobin content of the pellets. Histological analysis showed a reduction in the amount of functional vessels within the Matrigel. We conclude that the MMP inhibitor BAY 12-9566 inhibits angiogenesis, a property that further supports its clinical development as an antimetastatic agent.

Growth of human melanoma xenografts is suppressed by systemic angiostatin gene therapy.

The effect of local and systemic delivery of the angiostatin gene on human melanoma growth was studied in nude mice. Liposome-coated plasmids carrying the cDNA coding for murine and human angiostatin (CMVang and BSHang) were injected weekly, locally or systemically, in mice transplanted with melanoma cells. The treatment reduced melanoma growth by 50% to 90% compared to that occurring in control animals treated with liposome-coated plasmid carrying the lacZ gene or in untreated controls. The growth of both locally injected and controlateral uninjected tumors in mice bearing two melanoma grafts was significantly suppressed after intratumoral treatment. Tumor growth inhibition was also observed in mice treated by intraperitoneal delivery, suggesting that angiostatin gene therapy acts through a systemic effect. Both melanoma growth suppression and delay in the onset of tumor growth were observed in treated mice. PCR performed on tumors and normal tissues showed that the lipofected DNA was present in tissues from treated mice, and angiostatin expression was demonstrated by RT-PCR. Histopathological analysis of melanoma nodules revealed an increase in apoptotic cells and a reduction in vessel density in tumors from treated mice. Our results suggest that systemic, liposome-mediated administration of genes coding for antiangiogenic factors represents a promising strategy for melanoma treatment in humans.

Multiresistant Stenotrophomonas maltophilia tunneled CVC-related sepsis, treated with systemic and lock therapy.

In the last decade, a remarkable increase in the incidence of nosocomial Gram-negative infections has been observed. These pathogens represent a substantial problem in clinical practice, due to the high resistance profile of most commonly used antibiotics. This phenomenon is surely a co-factor that exposes these susceptible patients to infections caused by selected pathogens like multiresistant Gram-negative rods. A typical example is represented by VAP (ventilator-associated pneumonia) sustained by Acinetobacter spp., Pseudomonas aeruginosa, Bulkolderia cepacia. The Authors describe a case of a central venous cather (CVC)-related Stenotrophomonas maltophilia sepsis in a patient affected by solid tumor, successfully treated with systemic antibiotic therapy associated with "lock therapy". This combination was able to cure the infection, allowing the patient to continue chemotherapy and saving the in situ CVC. The surveillance of CVCs, good adherence to the protocols and guidelines and "good practice" are the cornerstones for the prevention of nosocomial infections.

Ringtail in suckling Munich Wistar Fromter rats: a histopathologic study.

Ringtail is a pathologic condition of the tail of rats and other rodents that is traditionally attributed to low environmental humidity, although dietary deficiencies, genetic susceptibility, environmental temperature, and degree of hydration of the animal also have been suggested as possible causes. To the authors' knowledge, a detailed histopathologic study that may serve to shed light on the etiopathogenesis of this disease has not yet been published. We describe the histologic findings of ringtail observed in 12 suckling Munich Wistar Fromter (MWF) rats from two litters. Epidermal hyperplasia characterized by orthokeratotic and parakeratotic hyperkeratosis and acanthosis was observed in all affected rats. Numerous often dilated vessels were present in the dermis of tails that appeared of red/brown color at gross examination. In severe cases, the dilated vascular structures were thrombotic and accompanied by dermal hemorrhages and focal coagulative necrosis of the overlying epidermis. These findings suggest that epidermal acanthosis and hyperkeratosis are the main and primary events in the development of ringtail. To clarify the cause of this disease, future studies should be focused on the numerous factors that can induce such epidermal changes.

Phase 2. Testing of solutions.

Phase 2 of reengineering project, the testing of solutions, was based on the definition of a Prototype, and the implementation of the Pilot phase. This gradual process has facilitated the organizational change and laid the foundations of subsequent extension phase. Ongoing initiatives concern the introduction of two new centers (wards and outpatient service) and the reorganization of ward and operating room activities.

Radiology room productivity.

Radiology has a significant impact on all health care processes at the "Policlinico A. Gemelli". The performance of Radiology rooms was thus analyzed within the overall performance of health care processes (e.g. medical wards, emergency service, day hospital). In this context, in the assessment phase of the reengineering project the Radiology room productivity has been analyzed. From outcomes of this analysis it appears that there is a high potential for increasing the Radiology room productivity (except for TC and MRI rooms). It has been observed that a better ward/service communication, together with a better use and planning of Radiology rooms and resources would allow a more efficient performance of the service. The reengineering project has led to a reorganization of the communication between Radiology rooms and wards/day hospital, a better inpatient transfer system from wards to Radiology rooms and the planning of the requests for exams. At present, a team is working in order to introduce a medium term budget of exams for all the wards associated to the provision of care for those diseases for which patient admission can be planned based on available Radiology rooms.

Hospital Reengineering Project at the "Policlinico A. Gemelli".

The "Policlinico A. Gemelli" in the context of ongoing change in the Italian Health Care Service, has developed a Strategic Plan for 1996-2000. In this context a major role is played by the reengineering project, divided into there sequential phases of implementation. The natural evolution of this project results in a department-oriented organization in order to complete and implement change.

Excellence in diagnostic imaging service management.

The identification of promoting factors of excellence improvement in radiology service management means to clearly assess how the different aspects of the service are managed. The key elements for intervention are sharply differentiated according to the service managerial level. The approach to continuous improvement should be a useful tool of assessment even when all its potentialities have been exhausted and new promoting factors are necessary to move to the subsequent stage.

Planning and scheduling radiologic exams.

Planning and scheduling of radiologic exams represent one of the crucial aspects in the performance of Diagnostic Imaging service, whose optimal management should lead to optimal efficiency and exploitation of technological and professional resources. A Diagnostic Imaging service with agreed and scheduled exams for customers achieves a more adequate, precise planning of the activity with optimum productivity of radiology rooms and anticipated workload assessment.

Immunohistopathological and neuroimaging characterization of murine orthotopic xenograft models of glioblastoma multiforme recapitulating the most salient features of human disease.

Tumorigenesis in human glioblastoma multiforme (GBM) is driven by several genetic abnormalities with disruption of important molecular pathways, such as p53/MDM2/p14ARF and EGFR/PTEN/Akt/mTOR. The malignant progression of human GBM is also primarily associated with a peculiar multistep pathophysiological process characterized by intratumoral ischemic necrosis (i.e. pseudopalisading necrosis) and activation of the hypoxia-inducible factor (HIF)-1alpha pathway with consequent peritumoral microvascular proliferation and infiltrative behaviour. Predictable preclinical animal models of GBM should recapitulate the main pathobiological hallmarks of the human disease. In this study we describe two murine orthotopic xenograft models using U87MG and U251 human cell lines. Ten Balb/c nude male mice were orthotopically implanted with either U87MG (5 mice) or U251 (5 mice) cell lines. Intracranial tumor growth was monitored through Magnetic Resonance Imaging (MRI). Immunohistopathological examination of the whole cranium was performed 30 days after implantation. U251 orthotopic xenografts recapitulated the salient pathobiological features described for human GBM, including invasive behaviour, wide areas of pseudopalisading necrosis, florid peripheral angiogenesis, GFAP and vimentin expression, nonfunctional p53 expression, striking active-caspase-3 and HIF-1alpha expression along pseudopalisades. U87MG orthotopic xenografts proved to be very dissimilar from human GBM, showing expansile growth, occasional necrotic foci without pseudopalisades, intratumoral lacunar pattern of angiogenesis, lack of GFAP expression, functional p53 expression and inconsistent HIF-1alpha expression. Expression of pAkt was upregulated in both models. The results obtained suggest that the U251 orthotopic model may be proposed as a predictive and reliable tool in preclinical studies since it recapitulates the most salient pathobiological features reported for human GBM.

Systemic gene therapy with anti-angiogenic factors inhibits spontaneous breast tumor growth and metastasis in MMTVneu transgenic mice.

Tumor growth and metastasis are angiogenesis-dependent. The possibility of inhibiting tumor growth by interfering with the formation of new vessels has recently raised considerable interest. We previously reported that it is possible to inhibit primary tumor growth and metastasis in a transgenic model of spontaneous breast tumor, which shows many similarities to its human counterpart (including ability to metastasize) by intratumoral administration of a DNA construct carrying the murine angiostatin cDNA driven by liposomes. Here we report that it is also possible to achieve this goal by a systemic (intraperitoneal) delivery of therapeutic DNA constructs carrying genes coding for mouse and human anti-angiogenic factors which include angiostatin, endostatin and TIMP-2. These findings may be relevant to the design of therapeutic interventions in humans.

Capillaria hepatica infection in wild brown rats (Rattus norvegicus) from the urban area of Milan, Italy.

Forty-seven wild brown rats (Rattus norvegicus) collected from the urban area of Milan (Italy) were screened for Capillaria hepatica liver infection. The liver of each rat was grossly and histologically examined for the presence of C. hepatica adults, eggs and typical C. hepatica induced lesions. In 17 rats (36%) liver lesions consistent with C. hepatica infection were detected. Grossly, white-yellow nodules of 1-5 mm in diameter were present, either scattered on the liver surface or localized in a single lobe. Histologically, granulomatous liver lesions associated with eggs and/or worms were observed. The degree of gross liver involvement was moderate in most of the positive cases (71%). About 30 cases of C. hepatica infection in humans have been documented world-wide, most of which are reported in children from 1 to 5 years of age. Our results suggest that the potential transmission of C. hepatica to children in the study area should be considered an important health issue.