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Biomedical subjects

M Bernasconi

Publications and source records attributed to M Bernasconi.

At least 19 recordsLinked to original sources
PubMed2006

Combined transbronchial needle aspiration and positron emission tomography for mediastinal staging of NSCLC.

There are no data available combining transbronchial needle aspiration (TBNA) of mediastinal lymph nodes and positron emission tomography (PET) in the staging of nonsmall cell lung cancer (NSCLC). The aim of the current study was to determine if these two methods can enhance the negative predictive value of the individual modality alone, for a specific lymph node station, and if this integrated approach can reduce the number of mediastinoscopies. A total of 113 patients with enlarged mediastinal lymph nodes (> or = 1 cm), who underwent both TBNA and PET scanning, were included. In 51 patients, histopathology, confirmed by surgical lymph node dissection, was compared with PET results and TBNA. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy to detect malignant lymphadenopathy was 68 (13/19), 89 (119/134), 46 (13/28), 95 (119/125) and 86% (132/152) for PET, respectively; 54% (6/11), 100 (53/53), 100 (6/6), 91 (53/58) and 92% (59/64), respectively for TBNA; and 100 (11/11), 94 (50/53), 79 (11/14), 100 (50/50) and 95 (61/64) for combined TBNA and PET, respectively. Combination of transbronchial needle aspiration and positron emission tomography has the potential to allow adequate mediastinal staging of nonsmall cell lung cancer with enlarged lymph nodes in most patients without the need for mediastinoscopy.

Aged↗
PubMed2005

Metal toxicity in municipal wastewater activated sludge investigated by multivariate analysis and in situ hybridization.

The toxicity of three heavy metals (copper, zinc and nickel) on an activated sludge biomass was studied by measuring several parameters of microbiological activity and the dynamics of microbial community composition. The effects on the microflora in the activated-sludge tank were evaluated by dosing the tank with different metal concentrations and a non-inhibiting concentration of copper for a 2-week period. The relationship between biological effects and chemical measurements was elucidated by principal component analysis (PCA). The biochemical data suggested a higher sensitivity of nitrifiers to these metals than heterotrophs. This was confirmed by fluorescent in situ hybridization (FISH) analysis on the microbial community. The impact of copper was displayed by biomass deflocculating phenomena (pin-point) and a decrease in the beta-proteo bacteria component. In addition, the zone settling velocity (ZSV) was shown not to be a good indicator of chronic toxicity phenomena. Finally, the sequence of biomass metal accumulation capability was assessed, and corresponds to Cu>Ni>Zn.

Biomass↗
PubMed2001

Ab initio simulations of photoinduced interconversions of oxygen deficient centers in amorphous silica.

We have studied by ab initio molecular dynamics the interconversion between oxygen deficient centers (Si-Si bond, dicoordinated silicon =Si:, and E' centers) induced by UV irradiation in a-SiO2. By dynamical simulations in the excited state of a periodic model of a-SiO2 we have identified the reaction path and activation barrier for the Si-Si-->=Si: interconversion. A new competitive transformation of the excited, neutral Si-Si bond into two E' centers has been identified. Our results provide strong theoretical support to the viability of these processes, proposed experimentally on the basis of optical data only.

Journal Article↗
PubMed2000

Ab initio simulation of phase transitions and dissociation of H2S at high pressure

By ab initio constant pressure molecular dynamics, we have identified the structure of phase V and phase VI of H2S at 35 and 65 GPa, respectively. The theoretical IR spectra of both phases are consistent with experimental findings and support our proposed structural models. We find that phase V is characterized by the presence of charged SH+3 and SH- species which are created and destroyed dynamically, whereas phase VI is no longer a molecular phase but consists of sheets of S with the majority of H intercalated between the layers. The stability of the two phases with respect to dissociation into elemental crystalline hydrogen and sulfur is discussed.

Journal Article↗
PubMed2000

Transcriptional modulation of the anti-apoptotic protein BCL-XL by the paired box transcription factors PAX3 and PAX3/FKHR.

The aberrant expression of the transcription factors PAX3 and PAX3/FKHR associated with rhabdomyosarcoma (RMS), solid tumors displaying muscle cell features, suggests that these proteins play an important role in the pathogenesis of RMS. We could previously demonstrate that one of the oncogenic functions of PAX3 and PAX3/FKHR in RMS is protection from apoptosis. BCL-XL is a prominent anti-apoptotic protein present in normal skeletal muscle and RMS cells. In the present study, we establish that BCL-XL is transcriptionally modulated by PAX3 and PAX3/FKHR, since enhanced expression of both PAX proteins stimulates transcription of endogenous BCL-XL mRNA in a cell type specific manner. Further, we present evidence that both PAX3 and PAX3/FKHR can transcriptionally activate the Bcl-x gene promoter in cotransfection assays. Using electrophoretic mobility shift assays, an ATTA binding site for PAX3 and PAX3/FKHR could be localized in the upstream promoter region (position -42 to -39). Finally, ectopic overexpression of either PAX3, PAX3/FKHR or BCL-XL can rescue tumor cells from apoptosis induced by antisense treatment. These results suggest that at least part of the anti-apoptotic effect of PAX3 and PAX3/FKHR is mediated through direct transcriptional modulation of the prominent anti-apoptotic protein BCL-XL. Oncogene (2000).

Base Sequence↗
PubMed2000

Two-membered silicon rings on the dehydroxylated surface of silica

We present extensive modeling of the amorphous silica surface, aimed at connecting its structural and chemical features. beta-cristobalite surfaces are initially studied to model the hydroxylated surfaces. A model reconstruction of the (111) surface is used to define a path leading to the formation of two-membered silicon rings upon dehydroxylation. Subsequently, a realistic model of the amorphous dehydroxylated (dry) surface is produced, by full ab initio annealing of an initial model generated by classical simulation. The presence of surface two-membered silicon rings emerges naturally. A calculation of IR activity yields an associated peak doublet in agreement with experimental data.

Journal Article↗
PubMed2000

Swiss Army Survey in Switzerland to determine the prevalence of Francisella tularensis, members of the Ehrlichia phagocytophila genogroup, Borrelia burgdorferi sensu lato, and tick-borne encephalitis virus in ticks.

A total of 6071 Ixodes ricinus ticks were collected on Swiss Army training grounds in five regions of Switzerland. The aim of the survey was to assess the prevalence of ticks infected with the human pathogens Francisella tularensis, members of the Ehrlichia phagocytophila genogroup, Borrelia burgdorferi sensu lato, and the European tick-borne encephalitis virus. TaqMan PCR (PE Biosystems, USA) and TaqMan RT-PCR (PE Biosystems) analyses were performed on DNA and RNA extracted from pools of ten ticks grouped by gender. Here, for the first time, it is shown that ticks may harbor Francisella tularensis in Switzerland, at a rate of 0.12%. Furthermore, 26.54% of the ticks investigated harbored Borrelia burgdorferi sensu lato, 1.18% harbored members of the Ehrlichia phagocytophila genogroup, and 0.32% harbored the European tick-borne encephalitis virus. A new instrumentation was applied in this study to carry out and analyze more than 2300 PCR reactions in only 5 days. Furthermore, the results reveal that people working in outdoor areas, including army personnel on certain training grounds contaminated with ticks containing tick-borne pathogens, are at risk for different tick-borne diseases.

Animals↗
PubMed2000

Latest generation of unipolar and bipolar steroid eluting leads: long-term comparison of electrical performance in atrium and ventricles.

One hundred and seventy-three patients, mean age 74 years permanently paced with 123 atrial (53 unipolar, 70 bipolar) and 143 ventricular (73 unipolar, 70 bipolar) pacing leads were included in this study. The pacing leads were recent generation low surface area steroid eluting leads from one manufacturer: leads with silicone and polyurethane insulation were studied, and they were combined with generations of one pacemaker family from the same manufacturer permitting identical measurements to be made over a follow-up of 2 years. Pacing threshold was measured using pulse duration at a fixed voltage of 1.5 V: peak to peak P and R wave amplitude and pacing impedance at 2.5 V and 0.5 ms were all measured using the manufacturer's standard programmer. Although many significant differences, in the parameters measures, existed between atrium and ventricle and unipolar and bipolar configurations, none was felt to be of clinical significance. These data permit the physician to choose the lead type with regard to sensing performance and long-term lead integrity.

Adult↗
PubMed1999

Superionic and metallic states of water and ammonia at giant planet conditions.

The phase diagrams of water and ammonia were determined by constant pressure ab initio molecular dynamic simulations at pressures (30 to 300 gigapascal) and temperatures (300 to 7000 kelvin) of relevance for the middle ice layers of the giant planets Neptune and Uranus. Along the planetary isentrope water and ammonia behave as fully dissociated ionic, electronically insulating fluid phases, which turn metallic at temperatures exceeding 7000 kelvin for water and 5500 kelvin for ammonia. At lower temperatures, the phase diagrams of water and ammonia exhibit a superionic solid phase between the solid and the ionic liquid. These simulations improve our understanding of the properties of the middle ice layers of Neptune and Uranus.

Ammonia↗
PubMed1999

High impedance low energy pacing leads: long-term results with a very small surface area steroid-eluting lead compared to three conventional electrodes.

We evaluated the handling performance at implant, and the long-term atrial and ventricular electrical performance of a new generation using a very small surface area (1.2 mm2) steroid-eluting electrode (Medtronic CapSure Z). We compared the performance of CapSure Z to that of traditional passive fixation leads, with and without steroid elution. The study was conducted during 2 years of follow-up. We studied 188 patients (105 males and 83 females; mean age 71 +/- 7 years). All of the patients were implanted with a dual chamber pacemaker and the same type of lead in both chambers. Forty-one patients received CapSure Z leads, 25 patients received Target Tip leads (8-mm2 surface area; no steroid elution), 63 patients received CapSure leads (8-mm2 surface area; steroid elution), and 59 patients received CapSure SP leads (5.8-mm2 surface area; steroid elution). The four groups were homogeneous in regards to sex, age, cardiac disease, and reason for implant. At follow-up, the CapSure Z lead showed sensing values comparable to the other leads, with lower pacing thresholds and higher pacing impedance in both chambers. We evaluated the mean current drained from the pacemaker by the different types of leads when using safe, low energy output settings. We found that by using CapSure Z leads, the mean current was significantly lower than that of the other types of leads (0.42 microA for CapSure Z ventricular lead vs 0.85 for CapSure SP, 1.42 for CapSure, and 1.54 for Target Tip). Thus, the use of the CapSure Z lead, combined with low energy output programming, will increase pacemaker longevity compared to the use of traditional leads and standard output programming.

Aged↗
PubMed1999

Time trends in the intracardiac potential recorded by pacemaker telemetry: comparison between steroid-eluting small area electrodes.

We assessed the time course of electrograms sensed both in the atrium and ventricle by two different steroid-eluting electrodes: Medtronic Capsure SP (with an area of 5.5 mm2) and Z (with an area of 1.2 mm2). We considered 68 unipolar electrodes: 31 atrial (19 Capsure SP 4523 and 12 Capsure Z 4533) and 37 ventricular (24 Capsure SP 4023 and 13 Capsure Z 4033) implanted in 47 consecutive patients (30 men and 17 women, with an age of 72 +/- 9.4 years). The pacemaker model was Medtronic Elite 7077-7086 (DDD-DDDR) in 25 patients and Medtronic Legend 8419-8424 (VVIR-AAIR) in 22 patients. The endocavitary signal (all patients had spontaneous rhythm) was telemetrically obtained by a Medtronic 9790 device and acquired on a personal computer at implantation and 7, 30, and 180 days thereafter. The signal was studied both in the time domain and in the frequency domain by spectral analysis. The following parameters were calculated: amplitude (A): peak-to-peak value of the complex; slew rate (SR) peak negative first derivative; F0: frequency at which the power spectrum reaches its maximum value; and bandwidth (Bw): expressed as the distance between the -3 dB points and statistically analyzed by a two-way analysis of variance with factors "time" (four measurements) and "electrode" (Capsure SP and Z) and repeated measurements on the former. Ventricular sensing: no time or electrode effect (P > 0.1 in all comparisons) was found for F0, Bw, or SR, while a time effect (P < 0.04) not dependent on the type of electrode was found for the amplitude of the signal. In particular, a significant increase was found between the measurement at 6 months and that at implantation (P < 0.004). Atrial sensing: A, F0, and bandwidth were not affected by time or electrode (P > 0.09), while SR behaved differently over time (P < 0.05) in the two electrodes (the Capsure Z showed an increase at sixth month [P < 0.04] compared to implantation). In conclusion, the Medtronic Capsure SP and Z electrodes proved to be valid and substantially equivalent as far as concerns the measurement of the intracardiac potential despite the difference between their surface areas. Further studies should be devised to assess whether transitory decreases of atrial Bw in the first month of follow-up observed in a few patients for both electrodes could be responsible for clinical episodes of sensing deficit.

Aged↗
PubMed1998

Multiple myeloma index: verification of a new prognostic approach with evaluation of treatment response.

BACKGROUND AND OBJECTIVE: Currently adopted prognostic criteria for multiple myeloma (MM) still lack reliable predictive ability to select subsets of patients for different therapies, in particular for intensive treatment protocols. In this work we aimed to test the prognostic value of the MM Prognostic Index (MMPI), developed in 1996 by Grignani et al. from Pavia University as a clinical and investigational tool. DESIGN AND METHODS: Ninety-three MM patients were eligible for the study. All received initial induction therapy based on a standard 6-month melphalan + prednisone (M + P) protocol. Clinical and laboratory parameters, conventional staging and bone marrow infiltration percentage and cytopathology (BMIC) were assessed at diagnosis, while treatment response (TR) was evaluated using criteria after induction therapy. Cox's multivariate survival analysis was applied on prognostic data. RESULTS: In our patients independent prognostic value was confirmed for British Medical Research Council staging, BMIC and TR, the three factors considered in MMPI. Risk classes obtained via MMPI identify patients with different outcomes; moreover, the index discriminates significantly among Stage II patients. INTERPRETATION AND CONCLUSIONS: This new approach to MM prognosis is simple and reliable from the prognostic point of view; it refers not only to neoplastic mass, but also to intrinsic proliferative capacity of the malignant clone and to tumor-host interactions. We recommend its adoption in clinical practice and in the evaluation and design of therapeutic trials.

Adult↗
PubMed1996

Induction of apoptosis in rhabdomyosarcoma cells through down-regulation of PAX proteins.

The expression of a number of human paired box-containing (PAX) genes has been correlated with various types of tumors. Novel fusion genes encoding chimeric fusion proteins have been found in the pediatric malignant tumor alveolar rhabdomyosarcoma (RMS). They are generated by two chromosomal translocations t(2;13) and t(1;13) juxtaposing PAX3 or PAX7, respectively, with a forkhead domain gene FKHR. Here we describe that specific down-regulation of the t(2;13) translocation product in alveolar RMS cells by antisense oligonucleotides results in reduced cellular viability. Cells of embryonal RMS, the other major histiotype of this tumor, were found to express either wild type PAX3 or PAX7 at elevated levels when compared with primary human myoblasts. Treatment of corresponding embryonal RMS cells with antisense olignucleotides directed against the mRNA translational start site of either one of these two transcription factors similarly triggers cell death, which is most likely due to induction of apoptosis. Retroviral mediated ectopic expression of mouse Pax3 in a PAX7 expressing embryonal RMS cell line could partially rescue antisense induced apoptosis. These data suggest that the PAX3/FKHR fusion gene and wild-type PAX genes play a causative role in the formation of RMS and presumably other tumor types, possibly by suppressing the apoptotic program that would normally eliminate these cells.

Animals↗
PubMed1996

Accuracy of telemetry signals in the post-implantation monitoring of electrograms sensed by pacemakers.

Monitoring of electrograms (EGMs) sensed by pacemakers (PMs) during their lifetime is the utmost importance, since changes of these signals, due to modifications of the electrode-myocardial interface may occur compromising the proper functioning of the PM. Since after implantation these intracardiac signals are accessible only by means of a telemetry system, it is necessary to ascertain how faithfully the telemetric signals reproduce the direct ones. To this aim we devised an accurate method, based on linear system theory, which allows the estimation of the transfer function of the PM-telemetry system and the comparison of a set of time and frequency domain parameters (wave amplitude, slew rate, frequency at the spectrum peak and bandwidth) computed on both direct and telemetric signals. To overcome the problem that these two signals cannot be recorded simultaneously, an appropriate model of the input and output signals of the PM-telemetry system and of their interrelationship was identified. This model relies on a set of reasonable assumptions about the nature of the direct signal (supposed to have a fixed morphology within a predefined analysis window) and of noise sources corrupting both the direct and telemetric signals. Owing to the involvement of deterministic and stochastic signals, the theory of quasi-stationary signals was employed to obtain the system transfer function. To test our method, direct and telemetric recordings were performed on 12 patients with atrial sensing carrying Medtronic Pacemakers (Mod Elite 7077/7086, programmer Mod 9760) with unipolar steroid eluting leads (Medtronic Capsure 4523). The results we obtained demonstrate that the specific system considered acts as a low-pass filter with a -3 dB frequency at about 90 Hz this ensures that the telemetric signal contains almost all the information of the direct one and can be used to monitor the changes of the signals sensed by the PM.

Aged↗