Biomedical subjects

M Marconi

Publications and source records attributed to M Marconi.

At least 19 recordsLinked to original sources

PubMed2007

Salvage hepatic resection after incomplete interstitial therapy for primary and secondary liver tumours.

BACKGROUND: When the response to percutaneous ablation therapy (PAT) of liver tumours is incomplete, surgery may be undertaken as a salvage therapy. To validate the safety and effectiveness of salvage hepatectomy, patients who had undergone PAT or no treatment before hepatectomy were compared. METHODS: Of 137 patients who had hepatectomy for primary and secondary tumours, 21 had undergone PAT and 116 had surgery as primary treatment. Tumour features and the incidence of liver cirrhosis were similar in the two groups. RESULTS: Peroperative mortality and major morbidity rates were zero and 5 per cent (one of 21) respectively among patients who had PAT before surgery, and 0.9 per cent (one of 116) and zero in those who did not. Duration of operation (mean 495 versus 336 min; P<0.001), clamping time (mean 81 versus 53 min; P<0.001), blood loss (mean 519 versus 286 ml; P=0.004), need for blood transfusion (six of 21 patients versus nine of 116; P=0.001), and rates of thoracophrenolaparotomy (eight of 21 versus 14 of 116; P<0.001) and resection of other tissues (six of 21 versus nine of 116; P<0.001) were significantly higher in the PAT group. CONCLUSION: Hepatectomy after incomplete PAT is safe and effective, but more extensive procedures are necessary. The effect of salvage hepatectomy on long-term outcome is still unclear.

Adult↗

PubMed2006

Temperature-dependent dynamics of water confined in nafion membranes.

We performed a neutron scattering study to investigate the dynamical behavior of water absorbed in Nafion at low hydration level as a function of temperature in the range 200-300 K. To single out the spectral contribution of the confined water, the measurements were done on samples hydrated with both H(2)O and D(2)O. Due to the strong incoherent scattering cross section of hydrogen atoms with respect to deuterium, in the difference spectra, the contribution from the Nafion membrane is subtracted out and the signal originates essentially from protons in the liquid phase. The main quantities we extracted as a function of the momentum transfer are the elastic incoherent structure factor (EISF) and the line width of the quasielastic component. Their trend suggests that the motion of hydrogen atoms can be schematized as a random jumping inside a confining region, which can be related to the boundaries of the space where water molecules move in the cluster they form around the sulfonic acid site. Through the calculated EISF, we obtained information on the size of such a region, which increases up to 260 K and then attains a constant value. Above this temperature, the number of water protons that are dynamically activated in the accessible time window increases with a faster rate. The jump diffusion dynamics is characterized by a typical jumping time which is stable at 5.3 ps up to approximately 260 K and then gradually decreases. The ensemble of the findings indicates that, within the limits of the energy resolution of the present experiment, water absorbed in the Nafion membrane undergoes a dynamical transition at around 260 K. We discuss the possible relationship of this dynamical onset with the behavior of the electrical conductivity of the membrane as a function of the temperature.

Journal Article↗

PubMed2006

Conditioning action of the environment on the protein dynamics studied through elastic neutron scattering.

The dynamics of lysozyme in the picosecond timescale has been studied when it is in dry and hydrated powder form and when it is embedded in glycerol, glycerol-water, glucose and glucose-water matrices. The investigation has been undertaken through elastic neutron scattering technique on the backscattering spectrometer IN13. The dynamics of dry powder and embedded-in-glucose lysozyme can be considered purely vibrational up to 100 K, where the onset of an anharmonic contribution takes place. This contribution can be attributed to the activation of methyl group reorientations and is described with an Arrhenius trend. An additional source of anharmonic dynamics appears at higher temperatures for lysozyme in hydrated powders and embedded in glycerol, glycerol-water and glucose-water matrices. This second process, also represented with an Arrhenius trend, corresponds to the so-called protein dynamical transition. Both the temperature where such a transition takes place and the magnitude of the protein mean square displacements depend on the environment. The dynamical response of the protein to temperature is put in relationship with its thermal stability.

Animals↗

PubMed2006

Controlling the protein dynamical transition with sugar-based bioprotectant matrices: a neutron scattering study.

Through elastic neutron scattering we measured the mean-square displacements of the hydrogen atoms of lysozyme embedded in a glucose-water glassy matrix as a function of the temperature and at various water contents. The elastic intensity of all the samples has been interpreted in terms of the double-well model in the whole temperature range. The dry sample shows an onset of anharmonicity at approximately 100 K, which can be attributed to the activation of methyl group reorientations. Such a protein intrinsic dynamics is decoupled from the external environment on the whole investigated temperature range. In the hydrated samples an additional and larger anharmonic contribution is provided by the protein dynamical transition, which appears at a higher temperature Td. As hydration increases the coupling between the protein internal dynamics and the surrounding matrix relaxations becomes more effective. The behavior of Td that, as a function of the water content, diminishes by approximately 60 K, supports the picture of the protein dynamics as driven by solvent relaxations. A possible connection between the protein dynamical response versus T and the thermal stability in glucose-water bioprotectant matrices is proposed.

Computer Simulation↗

PubMed2005

Capillary discharge-driven metal vapor plasma waveguides.

We report the generation of dense plasma waveguides containing a large concentration of silver ions by means of a fast (approximately 55 ns first half-cycle) microcapillary discharge. Concave plasma density profiles with axial electron density > 1 x 10(19) cm(-3) were measured from discharge ablation of 330 or 440 microm diameter Ag2S capillaries with 3-5 kA peak amplitude current pulses. The dynamic of this plasma waveguide was studied with interferometry, absorption measurements, and hydrodynamic model simulations. The results are relevant to the development of efficient longitudinally pumped metal vapor soft x-ray lasers, in particular those employing transient excitation of Ni-like ions. An approach to the design of a gain saturated wave-guided 13.9 nm laser in Ni-like Ag is discussed.

Journal Article↗

PubMed2005

The immunosuppressive effect of human cytomegalovirus infection in recipients of allogeneic hematopoietic stem cell transplantation.

In immune-competent individuals, human cytomegalovirus (HCMV) infection is associated with impairment of T-cell function. Our goal was to evaluate prospectively whether clinically asymptomatic HCMV infection in allogeneic hematopoietic stem cell transplantation (alloHSCT) recipients, treated pre emptively with ganciclovir, influences T-cell function as well. Mitogen-stimulated T-cell proliferative activity, together with cell surface markers, was tested in 49 patients on days + 30, + 45, + 60, and + 90 after alloHSCT and, additionally, in cases of positive HCMV pp65-antigenemia. HCMV infection was diagnosed in 19 patients. None of them developed HCMV disease. T-cell proliferative activity was significantly decreased on days when HCMV antigenemia was positive as compared to days without antigenemia. The number of pp65-positive cells negatively correlated with proliferative response. Comparison of patients who did experience HCMV infection with those who did not reveals significant decrease of T-cell proliferative activity observed on days + 30 and + 45, a time period when antigenemia was most frequently found to be positive, whereas no difference was detected on days + 60 and + 90. We conclude that, even clinically asymptomatic, HCMV infection has negative impact on T-cell proliferation capacity in alloHSCT recipients. However, pre emptive therapy with ganciclovir makes this immunosuppressive effect transient and restricted to the time of infection duration.

Adolescent↗

PubMed2005

IFN-gamma low production capacity in type 1 diabetes mellitus patients at onset of disease.

In type 1 diabetes mellitus (T1DM), cytokines can be directly cytotoxic to beta-cells, and/or play an indirect role influencing some cells of the immune system. Since several factors could impair cytokine serum levels, the purpose of our study was to longitudinally evaluate intracellular cytokines, in T1DM patients, and in subject at risk, by flow cytometry analysis. At T1DM onset we observed significantly lower percentage of peripheral CD4 + and CD8 + cells producing IFN-gamma in patients compared to controls and subjects at risk. The 15-month follow-up patients showed significantly lower percentage of CD4 + and CD8 + cells producing IFN-gamma compared to the other groups. At 8-year follow-up no significant differences were observed among the groups in the percentage of cells producing cytokines. We could have considered "exhausted cells" or these T cell subsets may be migrated from peripheral blood to pancreas. On the other hand, our results are in agreement with those reported in literature: in animal model the absence of IFN-gamma production makes beta-cells highly susceptible to viral infection and subsequent attack by natural killer cells, which lead to hyperglycaemia and diabetes mellitus.

Autoantibodies↗

PubMed2005

[Risk of workplace injuries by occupation in Italy in the 1990's].

BACKGROUND: In Italy it is not possible to assess the incidence of workplace injuries by occupation due to the absence of denominator data. OBJECTIVES: To evaluate severe workplace injuries by occupation, age and gender, via discussion of the validity of the available methods and informative systems. METHODS: The database included injuries in the industrial and artisan sectors in Italy during the period 1995-1999, as classified by INAIL (National Institute for the Insurance against Occupational Accidents and Diseases). A proportional case-control study was used. Three types of severe injuries were analyzed: fatal (3,685), permanently disabling (88,254) and injuries resulting in temporary disability for more than 40 days (238,609). Controls were represented by minor injuries with temporary disability lasting between 8 and 13 days (512,643). The relative risks were calculated by occupation and stratified by age and sex. The control group was chosen in order to minimize distortions and represented a balance between empirical criteria based on the experience of safety technicians and the quality and limits of INAIL archives. RESULTS: Among men in some construction occupations (operators of construction equipment, crane operators and masons), and in truck drivers, farm workers, messengers, and miners there were elevated risks in all age groups and for all levels of injuries severity. The model was more problematic to apply to women because the control group was less representative of the work population at risk. CONCLUSIONS: The case-control study model produced results consistent with those in the international literature, even if the use of minor injuries as the control group gives partly distorted risk estimates. The results supply information for decision making and for allocating resources for prevention and safety.

Accidents, Occupational↗

PubMed2005

[Appendicectomy: laparoscopic or ''open approach''?].

AIM: The aim of our study was to evaluate the advantages and disadvantages of open appendectomy versus laparoscopic appendectomy in the surgical treatment of acute appendicitis. We have compared the following items: operating time, postoperative pain, length of hospital stay, postoperative complications and costs. METHODS: The study was conducted on 435 patients admitted in our Department from December 1993 to December 2003 with diagnosis of acute appendicitis: 339 (77.9%) cases were operated with laparoscopic approach (LA group) and 96 (22.1%) cases with open approach (OA group) according to personal experience of surgeons on laparoscopic technique and patient's anthropometrical conformation. RESULTS: Mean operative time in LA group was 50 minutes (range 25-195) and 65 minutes (range 35-160) for OA group. In 15 patients (4.4%), the operation had to be converted to open approach. The morbidity was observed in 4.4% of patients for the LA group and 14.6% for the OA group. Hospital stay was faster for patients having laparoscopic appendectomy (2.5 days vs 3.5 days). Pain in the 1st and 2nd postoperative days, evaluated on the use of pain medication, was less in patient in LA group whereas the costs were higher in the LA group than in OA group. CONCLUSIONS: In our experience the laparoscopic approach to acute appendicitis can be considered safe and effective with diagnostic and therapeutic value. It significantly offers all the advantages of mini-invasive surgery reported in literature.

Adolescent↗

PubMed2004

Picosecond internal dynamics of lysozyme as affected by thermal unfolding in nonaqueous environment.

A neutron-scattering investigation of the internal picosecond dynamics of lysozyme solvated in glycerol as a function of temperature in the range 200-410 K has been undertaken. The inelastic contribution to the measured intensity is characterized by the presence of a bump generally known as "boson peak", clearly distinguishable at low temperature. When the temperature is increased the quasielastic component of the spectrum becomes more and more intrusive and progressively overwhelms the vibrational bump. This happens especially for T > 345 K when the protein goes through an unfolding process, which leads to the complete denaturation. The quasielastic term is the superposition of two components whose intensities and linewidths have been studied as a function of temperature. The slower component describes motions with characteristic times of approximately 4 ps corresponding to reorientations of polypeptide side chains. Both the intensity and linewidth of this kind of relaxations show two distinct regimes with a crossover in the temperature range where the melting process occurs, thus suggesting the presence of a dynamical transition correlated to the protein unfolding. Conversely the faster component might be ascribed to the local dynamics of hydrogen atoms caged by the nearest neighbors with characteristic time of approximately 0.3 ps.

Elasticity↗

PubMed2004

Infectious complications in adult acute lymphoblastic leukemia (ALL): experience at one single center.

Literature provides no specific data concerning the type and the risk factors for infection in adult patients with acute lymphoblastic leukemia (ALL). We retrospectively analyzed 97 adult ALL patients who underwent conventional chemotherapy during a 14-year period with the aim to assess the incidence and the factors affecting onset and outcome of infections. We found that during induction therapy 50% of patients developed infection, mainly caused by gram-negative bacteria and with a mortality rate of 11%. In multivariate analysis age > 60 years was significantly associated with more infections (P = 0.04) and higher related mortality (P = 0.03). Moreover, in 22% of patients infectious complications occurred during consolidation or maintenance therapy. Mortality rate of these infections, mostly due to opportunistic pathogens, was 16%. Factors affecting mortality was the cumulative dose of methylprednisolone given during induction therapy ( < or = 2600 mg = 31% vs. > 2600 mg = 69%; P = 0.03). Among neutropenic patients, adults with ALL represent a peculiar population since they frequently develop gram negative infections during induction and opportunistic infections during post-remission treatments. Advanced age and high-dose methylprednisolone result the major risk factors for infection related mortality in the former therapeutic phase and in the latter one, respectively.

Adolescent↗

PubMed2004

Neonatal outcome in patients with rheumatic disease.

Rheumatic autoimmune diseases have a higher prevalence in women, particularly during their childbearing age. Due to improved management, an increasing number of patients plan and carry out one or more pregnancies. Therefore, a growing interest is being paid to the possible consequences of maternal disease and associated treatment on the fetus and newborn infant. If maternal disease is characterized by the presence of IgG isotype autoantibodies, these can cross the placenta with possible antibody-mediated damage to the fetus. This is typically the case of the so called neonatal lupus erythematosus (NLE); a similar mechanism has been shown in infants of patients with immune thrombocytopenic purpura (ITP) and, less frequently, in those from mothers with antiphospholipid syndrome (APS). Indeed, this last condition is often responsible for placental, rather than neonatal, pathology. In addition, immunosuppressive and other drugs administered to the mothers during pregnancy and lactation might affect the fetal and neonatal immune system development. Finally, mothers disease and/or treatment could be related to neuropsychological alteration reported in some of their children.

Antiphospholipid Syndrome↗

PubMed2003

Antigen-specific T cell response in infants after recombinant hepatitis B virus vaccination at birth: evaluation of T helper lymphocyte diversity.

Recombinant hepatitis B virus antigen (rHBsAg)-specific CD4+ T cell clones (TCC) were isolated and expanded from the peripheral blood of nine children vaccinated at birth against the hepatitis B (HB) virus. Four of them responded with protective antibody production (responders), three subjects were unable to produce detectable antibody levels even after revaccination (nonresponders), and two infants produced antibodies only after revaccination (slow responders). TCC were then characterized for their ability to produce cytokines known to be important for T cell expansion (interleukin-2, IL-2) and/or effector functions (IL-4, IFN-gamma, IL-10). Results demonstrated that the frequency of rHBsAg-specific TCC in the samples of nonresponders was comparable to or higher than that in the samples of responders. Nevertheless, the majority of TCC obtained from responders or from slow responders before revaccination displayed the T helper 1 (T(H1))-dominant phenotype, while the majority of TCC obtained from nonresponders were nonpolarized T lymphocytes. After revaccination, the distribution of the different T(H) subsets in slow responders was heterogeneous. Overall, our present data suggest that an absence or delay in developing an rHBsAg-specific antibody response to vaccination is not associated with the capacity to generate an Ag-specific T cell response. However, compared to responders, nonresponding infants react to the rHBsAg vaccination with a reduced capacity to expand and differentiate toward polarized T(H) cells.

Cytokines↗

PubMed2002

Gemcitabine alone or combined with cisplatin in relapsed or refractory multiple myeloma.

Gemcitabine is a pyrimidine nucleoside analog with antitumor activity against solid tumor malignancies and leukemia. We evaluated its activity as a single agent and combining it with cisplatin in relapsed-refractory multiple myeloma (MM). Sixteen patients with advanced MM received intravenous gemcitabine 1250 mg/mq (days 1, 8 and 15) as a single agent for a total of 3 monthly courses. The responders received another three courses, and the non-responders received three courses of gemcitabine 1000 mg/mq (days 1, 8 and 15) plus cisplatin 80 mg/mq (day 1). No grade 4 hematological toxicity was seen after gemcitabine treatment, whereas > or = 3 grade neutropenia and thrombocytopenia were seen in 21 and 13% of the gemcitabine-cisplatin infusions, respectively. Non-hematological toxicity was negligible for both the regimens. After three courses of gemcitabine as a single agent, th e response rate was 31% (1 complete response, 1 partial response and 3 minimal response). Eight patients (50%) achieved stable disease and 3 (19%) had disease progression. Ten patients received gemcitabine-cisplatin and were evaluable for the response. Two patients progressed, four maintained stable disease whereas four patients, unresponsive to gemcitabine, obtained a response (3 partial response and 1 minimal response). With a median follow-up of 13 months (range 8-17.5), 7 patients (44%) died, 5 (31%) had disease progression, 1 (6%) relapsed, 1 was still in partial response (+11 months) and 2 (13%) had a stable disease. Median time to treatment failure (TTF) was 8 months (CI95%: 7.6-8.4) and median overall survival (OS) was 16 months (CI95%: 10-22). These results showed that gemcitabine and gemcitabine-cisplatin were feasible regimens and well tolerated in advanced relapsed-refractory MM. The response rates, the TTF and OS were similar to other salvage chemotherapy regimens; nevertheless, the quality of response was modest particularly after gemcitabine alone. Better results might be obtained combining gemcitabine with other chemotherapy compounds or with biologically based therapies.

Aged↗

PubMed2002

HPV and pregnancy: diagnostic methods, transmission and evolution.

Pregnancy may foster the development of infections, in particular HPV infections. The aim of this study was to evaluate the entity of the relationship between HPV infection and pregnancy, with all the possible complications associated with this relationship. The pathology may be latent or manifest. Possible methods of diagnosis are clinical, namely gynecological examinations, PAP-tests, colposcopy or molecular, using viral DNA assay, Southern Blot, PCR, Hybrid Capture, etc. The prevalence of HPV infection in pregnancy varies between 5.4 and 68.8%. The population with the highest risk, also among pregnant women, are those under the age of 26. A number of different opinions emerge from the literature regarding the possibility of maternal-fetal virus transmission. None of the patients examined carried out treatment during pregnancy. The data reported in the literature on the relationship between HPV and pregnancy are highly discordant. This discrepancy depends on the diagnostic techniques used, the clinical history of the pregnant woman and the period of pregnancy when the sample is collected. Pregnancy enhances the development of the pathology which then often recedes in the postpartum. The possible maternal-fetal transmission of the virus is an important aspect: the letter is the main factor responsible for juvenile laryngeal papillomatosis. A number of Authors report an initial presence of HPV in newborns which often disappears within 6 months after birth.

Adolescent↗

PubMed2001

Mutations of CD40 gene cause an autosomal recessive form of immunodeficiency with hyper IgM.

CD40 is a member of the tumor necrosis factor receptor superfamily, expressed on a wide range of cell types including B cells, macrophages, and dendritic cells. CD40 is the receptor for CD40 ligand (CD40L), a molecule predominantly expressed by activated CD4(+) T cells. CD40/CD40L interaction induces the formation of memory B lymphocytes and promotes Ig isotype switching, as demonstrated in mice knocked-out for either CD40L or CD40 gene, and in patients with X-linked hyper IgM syndrome, a disease caused by CD40L/TNFSF5 gene mutations. In the present study, we have identified three patients with an autosomal recessive form of hyper IgM who fail to express CD40 on the cell surface. Sequence analysis of CD40 genomic DNA showed that one patient carried a homozygous silent mutation at the fifth base pair position of exon 5, involving an exonic splicing enhancer and leading to exon skipping and premature termination; the other two patients showed a homozygous point mutation in exon 3, resulting in a cysteine to arginine substitution. These findings show that mutations of the CD40 gene cause an autosomal recessive form of hyper IgM, which is immunologically and clinically undistinguishable from the X-linked form.

CD40 Antigens↗

PubMed2001

Thermodynamics of the high-affinity interaction of TCF4 with beta-catenin.

The formation of a complex between beta-catenin and members of the TCF/LEF family of high-mobility group proteins is a key regulatory event in the wnt-signaling pathway, essential for embryonal development as well as the growth of normal and malignant colon epithelium. We have characterized the binding of TCF4 to human beta-catenin by steady-state intrinsic fluorescence quenching experiments, surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC). Binding studies in solution and in heterogeneous phase showed that TCF4 binds reversibly to beta-catenin with an affinity (KB) of 3(+/-1) 10(8) M(-1). Site-directed mutagenesis, together with calorimetric measurements, revealed that residue D16 in TCF4 plays a crucial role in high-affinity binding. Mutation of this residue to alanine resulted in a decrease of KB by two orders of magnitude as well as a significant reduction in binding enthalpy. Binding of TCF4 to beta-catenin gave rise to a large negative enthalpy change at 25 degrees C (-29.7 kcal/mol). Binding enthalpies were strongly temperature dependent, which resulted in the determination of a large heat capacity change upon binding of -1.5 kcal/(mol K). The molecular events that take place upon complex formation are discussed using the measured thermodynamic data together with the crystal structure of the beta-catenin arm repeat region/TCF complex.

Binding Sites↗

PubMed2001

Pregnancy and condyloma. Evaluation about therapeutic effectiveness of laser CO2 on 115 pregnant women.

BACKGROUND: At present one of the most common pathologies of the female genital apparatus is infection from HPV. It may be present in the latent form or symptomatic with flat or condylomatous lesions. The condylomatous lesions are particularly interesting in pregnant women on account of the symptoms, complications and methods for treating such lesions. The aim of this study was to evaluate the therapeutic efficacy of laser-vaporization in genital condylomata during pregnancy. METHODS: From March 1998 through October 2000 we used laser therapy to treat 115 pregnant women with florid genital condylomata. Treatment was given without regard to the gestation period. All the women were treated at least once. Persistent cases (failure of therapy) and recurrence (new infection) were classed according to the gestation week and site of lesion. RESULTS: Unsuccessful therapy, evaluated on the basis of repeated treatment, was 7.83%. There was no evidence of recurrence in those who received therapy in the third trimester. There were no abortions, particular complications or intrauterine deaths. CONCLUSIONS: We believe, that at present, the most effective treatment for condylomatoses in pregnant women is laser-vaporization.

Adult↗