Flexural strength and elastic modulus evaluation of structures made by conventional PMMA and PMMA reinforced with graphene.

OBJECTIVE: The aim of this study was to compare both the elastic modulus (EM) and the flexural strength (FS) of two materials used in dental prosthesis, namely polymethylmethacrylate (PMMA) and polymethylmethacrylate reinforced with graphene (G-PMMA). MATERIALS AND METHODS: Twenty rectangular samples were manufactured by a milling machine and divided into two groups (n= 10/group): Group 1, PMMA; Group 2, G-PMMA. The specimens were subjected to a three-point bending test conducted in the elastic range to evaluate EM. A similar test was protracted until fracture to evaluate FS. Data on EM and FS were statistically analyzed with independent-samples t-test in order to compare the two groups. A scanning electron microscope (SEM) (5.00 kx and 1.00 kx magnification) was used to evaluate the morphology of sample's fracture. RESULTS: Compared to PMMA samples, each G-PMMA sample showed significantly higher values of FS (p <0.001) and EM (p <0.001). SEM images analysis showed an inhomogeneous fracture morphology in G-PMMA samples. CONCLUSIONS: The results show that G-PMMA is a promising material to be used for prosthetic purposes. This is demonstrated by a significant increase in both peak load and bending stiffness, resulting from the bending test performed on G-PMMA samples. Furthermore, the latter exhibit greater homogeneity in their mechanical behavior, supporting the potential value of this material in dental prosthesis.

Will antiangiogenic agents be a future for mesothelioma therapy?

BACKGROUND: Malignant mesothelioma (MM) is an aggressive disease that is diagnosed mostly in locally advanced or metastatic stage. In this condition chemotherapy with the combination cisplatin and pemetrexed or ralitrexed represents the standard treatment as supported by a phase III study. However, chemotherapy has very limited effect on the improvement of survival of patients and very few of the MM patients survive more than 2 years. A better understanding of molecular mechanisms and pathways involved in angiogenesis in MM is the basis for the development of new drugs targeted against these pathways responsible for the proliferation and survival of tumor cells. OBJECTIVE: This review discusses the role of angiogenic factors in tumourigenesis with a particular focus on MM and it summarizes the results of clinical trials on the drugs targeting angiogenic pathways in MM. METHODS: We have used original research articles, abstracts and oral presentations from ASCO (American Society of Clinical Oncology) and the website of clinical trials http://www.ClinicalTrials.gov. RESULTS/CONCLUSIONS: This review summarizes the results of antiangiogenic agents under evaluation in clinical trials. A better understanding of the angiogenic pathways activated in MM will hopefully provide new therapeutic options for these patients in the future.

Worldwide experience with sequential phase-shift sound cancellation treatment of predominant tone tinnitus.

OBJECTIVE: To report clinical data from six centres in the US, Western Europe and Asia which have used phase-shift sound wave cancellation for treatment of predominant tone tinnitus, from the first treatment in 2000 to 2009. METHOD: Clinical data were obtained from New York City, London, Erie (Pennsylvania, USA), Antwerp, Grottamare (Italy) and Kuala Lumpur, and summarised. RESULTS: A total of 493 patients were treated. A reduction in tinnitus volume (defined as > or =6 dB) was seen in 49-72 per cent of patients.

Practical management of pleural empyema.

Empyema is defined as pus in the thoracic cavity due to pleural space infection and has a multifactorial underlying cause, although the majority of cases are post-bacterial pneumonia. Despite treatment with antibiotics, patients with empyema have a considerable morbidity and mortality due at least in part to inappropriate management of the effusion. Timely diagnosis of pleural space infection and rapid initiation of effective pleural drainage represent fundamental principles for managing patients with empyema. Ultrasound is particularly useful to identify early fibrin membranes and septations in the pleural cavity conditioning treatment strategy. Empyema and large or loculated effusion with a pH < 7.20 need to be drained. Thoracoscopy has largely been used in pleural effusion due to lung infection. Whereas the efficacy of video-assisted thoracic surgery (VATS) in empyema management has been evaluated in several retrospective studies showing favourable results, less is known about the role of medical thoracoscopy (MT) in pleural infection. MT, appears to be safe and successful in multiloculated empyema treatment. It is also lower in cost and in frail patients is better tolerated than VATS which requires tracheal intubation.

Taurolidine and oxidative stress: a rationale for local treatment of mesothelioma.

Malignant mesothelioma is an asbestos-related, aggressive tumour, resistant to most anticancer therapies. Akt is a key mediator of mesothelioma cell survival and chemoresistance. This study aimed to clarify the mechanism by which taurolidine (TN), a known synthetic compound with antimicrobial and antineoplastic properties, leads to mesothelioma cell death. Apoptosis was studied by annexin V binding, cell cycle analysis, caspase-8 activation, poly(ADP-ribose) polymerase (PARP) cleavage and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling (TUNEL). Oxidative stress was measured by nitrite production and DNA oxidative damage. Protein expression and phosphorylation were evaluated by immunoprecipitation and immunoblotting. TN induces cell death of mesothelioma cells, but not of non-neoplastic human mesothelial cells. After TN treatment of mesothelioma cells, Akt but not extracellular signal-regulated kinase (Erk) 1/2 activity is inhibited a in time- and dose-dependent manner. Protein phosphatase (PP)1alpha and PP2A are activated several hours after drug addition. Apoptosis induced by TN is driven by oxidative stress and cell exposure to sulfydryl donors, such as glutathione monoethylester and l-N-acetylcysteine, significantly reduced pro-apoptotic effects and Akt inhibition. Conversely, expression of constitutively activated Akt did not affect cytoxicity elicited by TN, which retained its ability to inhibit the kinase. TN induces mesothelioma cell death via oxidative stress, accompanied by inhibition of Akt signalling. This provides a promising molecular rationale for TN as local treatment of malignant mesothelioma.

Erionite and asbestos differently cause transformation of human mesothelial cells.

Malignant mesothelioma (MM) is an aggressive tumor associated with environmental or occupational exposure to asbestos fibers. Erionite is a fibrous zeolite, morphologically similar to asbestos and it is assumed to be even more carcinogenic. Onset and progression of MM has been suggested as the result of the cooperation between asbestos and other cofactors, such as SV40 virus infection. Nevertheless, several cases of MM were associated with environmental exposure to erionite in Turkey, where SV40 was never isolated in MM specimens. We show here that erionite is poorly cytotoxic, induces proliferating signals and high growth rate in human mesothelial cells (HMC). Long term exposure to erionite, but not to asbestos fibers, transforms HMC in vitro, regardless of the presence of SV40 sequences, leading to foci formation in cultured monolayers. Cells derived from foci display constitutive activation of Akt, NF-kappaB and Erk1/2, show prolonged survival and a deregulated cell cycle, involving cyclin D1 and E overexpression. Our results reveal that erionite is able per se to turn HMC into transformed highly proliferating cells and disclose the carcinogenic properties of erionite, prompting for a careful evaluation of environmental exposure to these fibers. The genetic predisposition to the effect of erionite is a separate subject for investigation.

Advanced techniques in medical thoracoscopy.

For expert pulmonologists, advanced procedures in medical thoracoscopy are the nonroutine and more complex applications of the method. The main current indications are the treatment of infected pleural space, forceps lung biopsy and sympathectomy. In parapneumonic effusions and empyema, medical thoracoscopy is as a drainage procedure, intermediate between tube thoracostomy and video-assisted thoracoscopic surgery (VATS), which is efficient, significantly lower in cost and avoids surgical thoracoscopy under general anaesthesia. It is essential that it is performed early in the course of the disease and is particularly advisable for frail patients at high surgical risk. The efficacy of forceps lung biopsy has been demonstrated in diffuse lung diseases, whereas results in localised lung diseases and chest-wall lesions have been less positive. However, VATS is currently the preferred approach for these indications. The technique still maintains its efficacy for visceral pleura and peripheral lung biopsy, in particular in the presence of pleural effusion and lung disorders. At the present time, thoracoscopic sympathectomy is minimally invasive and is an accepted intervention for patients with a variety of autonomous nervous system disturbances. Essential hyperhidrosis patients, and well-selected patients with other disorders, can be helped with this procedure, which can also be performed by interventional pulmonologists.

[Occupational cancer. The role of the occupational physician in systematic search and aetiological diagnosis of lung cancer. Analysis of a case list]. / I tumori occupazionali "ritrovati". Considerazioni sul ruolo del Medico del Lavoro nella ricerca sistematica e nella diagnosi eziologica dei tumori polmonari, alla luce di una casistica.

BACKGROUND: About 15% of lung cancers (LC) might be attributable to occupation. However, clinical practice shows that LC percentage for which occupational aetiology is recognized is lower than expected. OBJECTIVES: To address the role of Occupational Physicians (OP) in systematic search and aetiological diagnosis of LC. METHODS: The search was carried out at a university hospital in Brescia, northern Italy, a highly industrialized area with many workers potentially exposed to occupational lung carcinogens. Through short occupational history forms, physicians of various departments refer all new cases of primary LC to OP When occupational exposure to lung carcinogens is presumed, the OP evaluates the case at the occupational health clinic and sends clinical reports to notifying physicians, containing aetiological diagnosis and indications for medico-legal obligations. RESULTS: Before 1998, few cases were referred to the OP and even less were compensated. The search yielded 1502 LC; after screening, full occupational health evaluation was performed in 693 cases: occupational aetiology was recognized in 182 (26%). Risk factors were silica, asbestos, polycyclic aromatic hydrocarbons, truck driving, painting, road paving; many workers were exposed to multiple carcinogens. 48 cases were compensated, many others are under litigation. CONCLUSIONS: A systematic LC search made it possible to: reach an aetiological diagnosis and reduce the gap between expected LC and those reported/compensated; inform health authorities and undertake preventive action in workplaces; detect sentinel events; provide epidemiological data at community level; promote cooperation among health professionals (oncologists, surgeons, pneumologists, general practitioners, plant OP); increase teaching opportunities for medical students, those taking a specialisation course in occupational health; provide counselling and expert opinions for individual subjects, trade unions, employers, law courts.

Malignant mesothelioma and the working environment: the viewpoint of the occupational physician.

BACKGROUND: Firm scientific evidence supports the causal association between malignant mesothelioma (MM) and occupational exposure to asbestos. Risk attributable to occupation varies from 30 to 80% across different populations. The existence of a threshold level below which there is no risk of MM is still debated. A prompt and thorough assessment of exposure is essential to evaluate and manage MM cases, from diagnostic and epidemiological points of view. OBJECTIVES AND METHODS: To highlight the multiple areas of intervention by Occupational Physicians (OP) in MM evaluation and management, to describe an experience of OP in the province of Brescia. RESULTS: The main areas of interest of the OP are exposure assessment, diagnosis (clinical, etiological), medico-legal issues, social consequences, preventive strategies, risk communication, scientific dispute/uncertainties. By means of an active search, the Brescia MM registry, managed by OP belonging to the local health authority observed 309 MM from 1977 to 2003; the local Institute of Occupational Health, hosted in a hospital of national relevance, evaluated about 200 MM in the last decade. The main outcomes of OP activity are the high percentage of direct interviews, individual case management, expert exposure assessment, etiological diagnosis, counselling, medico-legal assistance, better knowledge of occupational risks, enhanced cooperation among health professionals (oncologists, pathologists, surgeons, pneumologists, general practitioners and OP), important contribution to Registries and to epidemiology (estimates of attributable risks, incidence, survival rates), with positive social and scientific consequences (insurance agencies, trade union organizations, public events, teaching opportunities). CONCLUSIONS: This experience highlights the multifaceted role of OP in active research and evaluation of MM cases, in the context of a multidisciplinary approach.

Malignant mesothelioma in 2004: How advanced technology and new drugs are changing the perspectives of mesothelioma patients. Highlights from the VIIth Meeting of the International Mesothelioma Interest Group.

Malignant mesothelioma (MMe) is a seemingly uncommon tumour whose incidence has in fact increased steadily and progressively over the last 30 years. Indeed, an actual "epidemic" is expected in the next 20 years, with over 1300 new cases a year till 2020 at least. Despite unquestionable improvement in the diagnostic methods at our disposal and the availability of new treatment strategies, the prognosis of MMe patients remains dramatically poor. For all the above reasons, translational research is the key to success; indeed, ever increasing knowledge of the molecular mechanisms underlying MMe pathogenesis could lead (and is actually leading) to new, hopefully more active, treatment options. To foster discussion among investigators working in this field, and to exchange different viewpoints concerning the newest advances in MMe pathogenesis and treatment, the VII International Mesothelioma Interest Group (IMIG) meeting was held in Brescia (Italy) between 24 and 26 June 2004 in cooperation with the Italian Group for the Study and Therapy of MMe (GIMe). The aim of this report is to summarize the most significant advances in the different disciplines applied to MMe presented and discussed during the IMIG meeting and how these advances will be changing the perspective of patients with MMe.

Talcage by medical thoracoscopy for primary spontaneous pneumothorax is more cost-effective than drainage: a randomised study.

Simple thoracoscopic talcage (TT) is a safe and effective treatment of primary spontaneous pneumothorax (PSP). However, its efficacy has not previously been estimated in comparison with standard conservative therapy (pleural drainage (PD)). In this prospective randomised comparison of two well-established procedures of treating PSP requiring at least a chest tube, cost-effectiveness, safety and pain control was evaluated in 108 patients with PSP (61 TT and 47 PD). Patients in both groups had comparable clinical characteristics. Drainage and hospitalisation duration were similar in TT and PD patients. There were no complications in either group. The immediate success rate was different: after prolonged drainage (>7 days), 10 out of 47 PD patients, but only 1 out of 61 TT patients required a TT as a second procedure. Total costs of hospitalisation including any treatment procedure were not significantly different between TT and PD patients. Pain, measured daily by visual analogue scales, was statistically higher during the first 3 days in TT patients but not in those patients receiving opiates. One month after leaving hospital, there was no significant difference in residual pain or full working ability: 20 out of 58 (34%) versus 10 out of 47 (21%) and 36 out of 61 (59%) versus 26 out of 39 (67%) in TT versus PD groups, respectively. After 5 yrs of follow-up, there had been only three out of 59 (5%) recurrences of pneumothorax after TT, but 16 out of 47 (34%) after conservative treatment by PD. Cost calculation favoured TT pleurodesis especially with regard to recurrences. In conclusion, thoracoscopic talc pleurodesis under local anaesthesia is superior to conservative treatment by chest tube drainage in cases of primary spontaneous pneumothorax that fail simple aspiration, provided there is efficient control of pain by opioids.

Expression of glycoprotein 90K in human malignant pleural mesothelioma: correlation with patient survival.

The expression of the tumour-associated glycoprotein 90K in patients with malignant pleural mesothelioma (MM) has not been described. This study used enzyme-linked immunoassay (ELISA) to measure 90K in pleural effusions (PEs) and sera from patients with MM (n=28), lung cancer (LC) (n=14) and benign pleural disease (BPD) (n=15). Immunohistochemistry was used to investigate 90K expression in MM and LC tissue sections. The expression of 90K was further evaluated in vitro by ELISA and western blot analysis of conditioned media and cellular extracts of MM, LC and normal human mesothelial (NHM) cell cultures. Finally, the relationships between 90K expression in MM and patient age and survival were studied. The mean 90K level was significantly higher (p<0.05) in PEs of MM patients (11.0+/-6.6 microg/ml) than in LC (6.1+/-3.2 microg/ml) or BPD (6.2+/-5.0 microg/ml) patients. Immunohistochemistry showed a positive reaction for 90K in MM biopsy sections and positive staining limited to inflammatory infiltrates in LC sections. The level of 90K was significantly higher in cell culture media of MM than of LC or NHM (p<0.001). Bands representing proteins with molecular weight of approximately 90 kDa were detected by western blot in MM cellular extracts. An inverse correlation between PE 90K levels and MM patient age (r=-0.45; p=0.017) and a positive correlation between serum 90K levels and MM patient survival (r=0.62; p=0.006) were detected by linear regression analysis. Kaplan-Meier univariate analysis showed increased survival probability for MM patients with serum 90K level >7.3 microg/ml (log rank, p<0.05). This is the first report in MM of the expression of 90K and of its potential diagnostic and prognostic application.

Vascular endothelial growth factor is an autocrine growth factor in human malignant mesothelioma.

Vascular endothelial growth factor (VEGF), a potent mitogen for vascular endothelium, is expressed in malignant pleural mesothelioma (MM). The present report examines the effect of VEGF on MM growth. Four MM cell lines produced significantly higher VEGF levels than normal mesothelial cells (1946+/-14 pg/ml vs. 180+/-17 pg/ml; p<0.001). In addition, MM cells expressed the tyrosine kinase-related VEGF receptors Flt-1 and KDR. Recombinant human VEGF phosphorylated both Flt-1 and KDR and increased proliferation of all four MM cell lines in a dose-dependent fashion. Neutralizing antibodies against either VEGF, Flt-1 or KDR significantly reduced MM cellular proliferation. In addition, expression of VEGF, Flt-1, and KDR was observed in MM biopsies. Moreover, higher VEGF levels were found in the pleural effusions of MM patients than in the effusions of patients with non-malignant pleural disease (1885.7+/-894.9 pg/ml vs. 266.9+/-180.5 pg/ml; p<0.001). Linear regression analysis showed a significant inverse correlation between serum VEGF levels and MM patient survival (r=0.72; p<0.01). No correlation was found between tumour vessel density and either serum (r=0.26; p=0.42) or pleural effusion (r=0.35; p=0.26) VEGF levels. These results indicate that VEGF, via activation of its tyrosine kinase receptors, may be a key regulator of MM growth. In addition, VEGF production could have an impact on patient survival, not only by promoting tumour angiogenesis but also by directly stimulating tumour growth.

Prognostic significance of presence and reduplication of basal lamina in malignant pleural mesothelioma.

The prognosis of patients with malignant pleural mesothelioma (MM) is dependent more on tumor extension and differentiation than on therapeutic effects. Reduplication of the basal lamina (RBL) is an ultrastructural feature of some benign and malignant tumors that has been inversely correlated with aggressiveness and was recently described in MM. To investigate whether RBL is important for predicting the survival of patients with MM, transmission electron microscopy was used to identify the presence of basal lamina or RBL in biopsy specimens obtained by thoracoscopy from 35 patients. Cox's regression analysis was used to study the relation of these ultrastructural features to survival. Better outcomes were found for patients whose tumors expressed either basal lamina (HR 0.48; 95% CI, 0.09-2.47) or RBL (HR 0.38; 95% CI 0.12-1.22) compared with the reference category, where basal lamina or RBL was not found. The expression of basal lamina and RBL is an important novel prognostic factors in MM. HUM PATHOL 31:1341-1345.