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Biomedical subjects

G Nicolini

Publications and source records attributed to G Nicolini.

At least 19 recordsLinked to original sources
PubMed2006

Beclomethasone/formoterol versus budesonide/formoterol combination therapy in asthma.

The present study was designed to compare the fixed combination of beclomethasone and formoterol in a hydrofluoroalkane Modulite (Chiesi Farmaceutici, Parma, Italy) pressurised metered-dose inhaler (pMDI), with a combination of budesonide and formoterol administered via a Turbuhaler (AstraZeneca, Lund, Sweden) dry powder inhaler (DPI). This was a phase III, multinational, multicentre, double-blind, double-dummy, randomised, two-arm parallel groups, controlled study design. After a 2-week run-in period, 219 patients with moderate-to-severe asthma were randomised to a 12-week treatment with beclomethasone 200 microg plus formoterol 12 microg b.i.d. delivered via a pMDI or budesonide 400 microg plus formoterol 12 microg b.i.d. delivered via a DPI. The analysis of noninferiority on primary outcome, morning peak expiratory flow in the last 2 weeks of treatment, showed no difference between groups. A statistically significant improvement from baseline in lung function, symptoms and rescue medication use was observed in both groups at all time-points. No differences were observed between treatments in either rate of asthma exacerbations or frequency of adverse events. The new fixed combination of beclomethasone and formoterol in hydrofluoroalkane Modulite pressurised metered-dose inhaler is equivalent to the marketed combination of budesonide and formoterol in terms of efficacy and tolerability profile.

Adult↗
PubMed2006

Comparison of advanced irradiation techniques with photons for benign intracranial tumours.

BACKGROUND AND PURPOSE: The potential benefits and limitations of different radiation techniques (stereotactic arc therapy (SRS/T), intensity modulated radiotherapy (IMRT), helical tomotherapy (HT), Cyberknife and intensity-modulated multiple arc therapy (AMOA)) have been assessed using comparative treatment planning methods on twelve patients presenting with 'benign' brain tumours. MATERIALS AND METHODS: Plans for five acoustic neurinomas, five meningiomas and two pituitary adenomas were computed to generate dose distributions for all modalities using a common CT dataset to delineate planning target volume and organs at risk. RESULTS: HT, AMOA and IMRT resulted superior to SRS/T and Cyberknife for target coverage. For the first group V(95%) ranged from 98% to 100%, minimum dose ranged from 91% to 96% and standard deviation from 0.84% to 1.67%. For organs at risk all techniques respected planning objectives with a tendency of Cyberknife and SRS/T to better spare the brain stem and the healthy brain tissue (e.g., V(20Gy) of 2.0% and 2.3%, respectively, compared to 3.1-5.0% for the other techniques). AMOA is in general preferable to IMRT for all OARs. Conformity index (CI(95)) was better for HT and Cyberknife (both 1.8) and less for AMOA and IMRT (3.9 and 3.0, respectively). CONCLUSION: All techniques provided good OAR sparing and primarily differed in target coverage indices. For the class of tumours investigated in this report, HT, AMOA and IMRT had better target coverage with HT providing the best combination of indeces. Between AMOA and IMRT, target coverage was comparable and, considering organs at risk, AMOA was slightly preferable.

Brain Neoplasms↗
PubMed2006

Mutually exclusive NRASQ61R and BRAFV600E mutations at the single-cell level in the same human melanoma.

Activating BRAF or NRAS mutations have been found in 80% of human sporadic melanomas, but only one of these genetic alterations could be detected in each tumour. This suggests that BRAF and NRAS 'double mutants' may not provide advantage for tumour growth, or may even be selected against during tumorigenesis. However, by applying mutant-allele-specific-amplification-PCR method to short-term melanoma lines, one out of 14 tumours was found to harbour both BRAFV600E and the activating NRASQ61R mutations. On the other hand, analysis of 21 melanoma clones isolated by growth in soft agar from this tumour indicated that 16/21 clones harboured a BRAFV600E, but were wild-type for NRAS, whereas the remaining had the opposite genotype (NRASQ61R/wild-type BRAF). When compared to BRAFV600E clones, NRASQ61R clones displayed reduced growth in soft agar, but higher proliferative ability in vitro in liquid medium and even in vivo after grafting into SCID/SCID mice. These data suggest that NRAS and BRAF activating mutations can coexist in the same melanoma, but are mutually exclusive at the single-cell level. Moreover, the presence of NRASQ61R or BRAFV600E is associated with distinct in vitro and in vivo growth properties of neoplastic cells.

Animals↗
PubMed2005

IMRT for breast. a planning study.

BACKGROUND AND PURPOSE: To evaluate the performance of ten different treatment-planning systems when intensity modulated (IMRT) plans are designed for breast treatments that include the irradiation of the internal mammary chain. PATIENTS AND METHODS: A dataset of five patients (CT images and volumes of interest) was distributed to design IMRT plans on the ten systems. To minimise biases, the same geometry and clinical planning aims were imposed on the individual plans. Results were analysed in terms of dose distributions and dose volume histograms. RESULTS AND CONCLUSIONS: For target coverage, the volume receiving more than 95% of the prescribed dose ranged from 77% (OTP) to 91% (Eclipse and Pinnacle), the volume receiving more than 107% ranged from 3.3% (Hyperion) to 23.2% (OTP). The mean dose to ipsilateral lung ranged from 13 Gy (Eclipse) to 18 Gy (OTP). The volume of the contralateral breast receiving more than 10 Gy ranged from 3% (Pinnacle) to 26% (Precise). The volume of heart receiving more than 20 Gy ranged from 7% (Eclipse) to 47% (Precise), the maximum significant dose to heart ranged from approximately 27 Gy (XiO) to approximately 49 Gy (Precise). The maximum significant dose to healthy tissue ranged from approximately 51 Gy (Eclipse) to approximately 62 Gy (OTP). It was also possible to show that the treatment geometry proposed here enables to minimise contralateral breast irradiation while keeping minimal ipsilateral lung (or heart) involvement and satisfactory target coverage.

Breast Neoplasms↗
PubMed2005

Biochemical interaction between effects of beclomethasone dipropionate and salbutamol or formoterol in sputum cells from mild to moderate asthmatics.

BACKGROUND: Several in vitro studies demonstrate that corticosteroids and long-acting beta(2) agonists may have a complementary and synergistic mode of action on the inflammatory processes in asthma. METHODS: Sputum was induced in 20 mild to moderate asthmatic patients and the induced sputum cells (ISC) were cultured with beclomethasone dipropionate (BDP) 10(-7) M, salbutamol 10(-8) M and formoterol 10(-8) M either alone or in combination, BDP plus salbutamol and BDP plus formoterol, for 24 h. We measured the levels of growth macrophages-colony stimulating factor (GM-CSF), released on activation normal T cells expressed and activated (RANTES) and interleukin-8 (IL-8), in the supernatant of stimulated cells by ELISA. Furthermore, we assessed nuclear translocation of glucocorticoid receptor (GR) and the expression of beta(2) receptor in ISC by immunofluorescence and RT-PCR, respectively. RESULTS: The release of GM-CSF, RANTES and IL-8 in ISC was significantly reduced by BDP plus salbutamol or formoterol as compared with either drug alone (P < 0.0001). beta(2) receptor expression was increased after 30 min of incubation with BDP and continued to increase over a time period of 4 h (P < 0.0001). Furthermore after 30 min of incubation, nuclear translocation of GR was greater with BDP plus salbutamol or formoterol than with any of the drugs alone (P < 0.0001). CONCLUSION: The present ex vivo study demonstrates a complementary mode of action between BDP and salbutamol or formoterol leading to an enhanced anti-inflammatory activity.

Adult↗
PubMed2004

Resveratrol interference with the cell cycle protects human neuroblastoma SH-SY5Y cell from paclitaxel-induced apoptosis.

In previous studies we demonstrated that resveratrol acts in an antiapoptotic manner on the paclitaxel-treated human neuroblastoma (HN) SH-SY5Y cell line inhibiting the apoptotic pathways induced by the antineoplastic drug. In the present study we evaluated the antiapoptotic effect of resveratrol, studying its activity on cell cycle progression. We determined the mitotic index of cultures exposed to resveratrol and paclitaxel alone or in combination, the cell cycle distribution by flow cytometric analysis (FACS), and the modulation of some relevant cell cycle regulatory proteins. Resveratrol is able to induce S-phase cell arrest and this interference with the cell cycle is associated with an increase of cyclin E and cyclin A, a downregulation of cyclin D1, and no alteration in cyclin B1 and cdk 1 activation. The resveratrol-induced S-phase block prevents SH-SY5Y from entering into mitosis, the phase of the cell cycle in which paclitaxel exerts its activity, explaining the antiapoptotic effect of resveratrol.

Antineoplastic Agents, Phytogenic↗
PubMed2004

Erythrocyte Na/K-ATPase is increased in subjects with subclinical hypothyroidism.

OBJECTIVE: In erythrocytes of patients with overt hyperthyroidism, the number of ouabain-binding sites and the activity of the Na(+)/K(+)-ATPase have been demonstrated to be decreased, whereas the opposite is true in patients with overt hypothyroidism. No information has been reported on the status of the Na(+)/K(+)-ATPase in subclinically hypothyroid (Sub Hypo) patients. DESIGN: We investigated the number of ouabain-binding sites and Na(+)/K(+)-ATPase activity in erythrocytes of chronic Sub Hypo subjects. PATIENTS AND METHODS: We measured (3)H-ouabain-binding sites in erythrocytes from 15 patients with subclinical hypothyroidism, and compared with those found in 17 normal subjects (N), seven with overt hypothyroidism (Hypo) and 10 with overt hyperthyroidism (Hyper). The activity of the sodium pump was assessed by measuring ouabain-sensitive (86)Rb uptake in a subpopulation of the same groups. RESULTS: The number of ouabain-binding sites in Sub Hypo patients (252 +/- 17; mean +/- SEM) was significantly higher (P < 0.02) than in Hyper (135 +/- 12) and N (203 +/- 10) groups, whereas it was not significant different from Hypo (293 +/- 31). There was a positive correlation between the number of ouabain-binding sites and TSH concentrations (P < 0.002) when Sub Hypo and N groups were considered together. There was a negative correlation between the number of ouabain-binding sites and free thyroxine (FT4; P < 0.0001) and free triiodothyronine (FT3) concentrations (P < 0.001) when all subjects were considered. Ouabain-sensitive (86)Rb uptake (picomoles (86)Rb/h 10(6) cells) in Sub Hypo was significantly higher (4.2 +/- 0.5) when compared with N (2.5 +/- 0.2, P < 0.01) and Hyper (2.5 +/- 0.5, P < 0.02). CONCLUSIONS: Erythrocytes of subclinically hypothyroid patients show a significant increase in the number of ouabain-binding sites and in ouabain-sensitive (86)Rb uptake. The state of erythrocyte Na(+)/K(+)-ATPase may therefore represent a biochemical marker of subclinical hypothyroidism.

Adult↗
PubMed2004

Pneumococcal bacterial peritonitis in an AIDS patient following esophageal endoscopic variceal sclerotherapy: case report and recommendations for antibiotic prophylaxis.

Chronic viral hepatitis is a common co-morbidity in Italian HIV-infected patients. It represents an important emergent associated risk of mortality in patients with HIV infection whose survival has increasingly improved by highly active antiretroviral therapy. In such patients further infectious predisposing factors, related to hepatic failure and esophageal haemorrhage, worsen the immunodeficiency due to HIV infection. Bacterial peritonitis has been reported in 3% of patients after esophageal endoscopic injection sclerotherapy emergency and in 0,5% of elective procedure. Combined antibiotic prophylaxis with aminopenicillins beta-lactamase inhibitor and fluoroquinolone should be regularly given to AIDS patients with decompensated liver cirrhosis who have esophageal variceal bleeding. A case of a pneumococcal bacterial peritonitis following emergency esophageal endoscopic sclerotherapy for variceal bleeding in patient with AIDS and liver cirrhosis with ascites is reported.

AIDS-Related Opportunistic Infections↗
PubMed2003

Effect of trans-resveratrol on signal transduction pathways involved in paclitaxel-induced apoptosis in human neuroblastoma SH-SY5Y cells.

trans-Resveratrol (3,4',5-trihydroxystilbene) is able to significantly reduce paclitaxel-induced apoptosis in the human neuroblastoma (HN) SH-SY5Y cell line, acting on several cellular signaling pathways that are involved in paclitaxel-induced apoptosis. trans-Resveratrol reverses phosphorylation of Bcl-2 induced by paclitaxel and concomitantly blocks Raf-1 phosphorylation, also observed after paclitaxel exposure, thus suggesting that Bcl-2 inactivation may be dependent on the activation of the Raf/Ras cascade. trans-Resveratrol also reverses the sustained phosphorylation of JNK/SAPK, which specifically occurs after paclitaxel exposure.Overall, our observations demonstrate that (a) the toxic action of paclitaxel on neuronal-like cells is not only related to the effect of the drug on tubulin, but also to its capacity to activate several intracellular pathways leading to inactivation of Bcl-2, thus causing cells to die by apoptosis, (b) trans-resveratrol significantly reduces paclitaxel-induced apoptosis by modulating the cellular signaling pathways which commit the cell to apoptosis.

Antineoplastic Agents, Phytogenic↗
PubMed2003

Malnutrition is not related to alterations in energy balance in patients with stable liver cirrhosis.

BACKGROUND AND AIMS: Little information are available on the relationship between energy balance and the alterations in nutritional status occurring in cirrhotic patients. The aim of the present study was to evaluate the daily energy balance in clinically stable cirrhotic patients with or without malnutrition. PATIENTS: Seventy-four consecutive cirrhotic patients and nine healthy controls were studied. METHODS: Basal energy expenditure was measured by indirect calorimetry and adjusted according to the patients' physical activity to estimate the daily energy expenditure. Food intake was evaluated based on a 3-day dietary diary. Nutritional status and body composition were assessed using skinfold anthropometry and dual energy X-ray absorptiometry, respectively. RESULTS: Thirty-two patients in the cirrhotic group were classified as severely malnourished according to anthropometric parameters. Two different patterns of soft-tissue loss were observed in the malnourished cirrhotic group: a significant reduction in fat mass and in fat-free mass was observed in males, whereas, females showed a significant reduction in fat mass only. Basal energy expenditure was similar in all groups, while the non-protein respiratory quotient was lower in cirrhotics notwithstanding their nutritional status. This suggests that lipids were the preferred oxidized fuel in the post-absorptive state in these patients. No difference in the estimated daily energy expenditure and energy intake was observed among groups. Lipid content of the diet was significantly lower in malnourished cirrhotics than in controls (33.1+/-1% vs 37.8+/-1%, P=0.02). CONCLUSIONS: Cirrhotic patients in stable clinical condition with malnutrition show a normal energy balance.

Analysis of Variance↗
PubMed2003

Effect of canrenone on the digitalis site of Na+/K(+)-ATPase in human placental membranes and in erythrocytes.

It has been reported that canrenone, which is used in hypertensive therapy as an antialdosteronic drug, may also act as a blocker of ouabain effects. Several studies suggest that human plasma contains an endogenous ouabain-like factor similar to ouabain, which may be increased in hypertension, in pregnancy, and in the neonatal state. This study evaluated (1) the effect of canrenone on Na+/K(+)-ATPase in relation to ouabain in human placental membranes and erythrocytes by 3H-ouabain binding assay; (2) the capacity of canrenone (10 microM) to reverse the inhibition of Na+/K(+)-ATPase by ouabain and by ouabain-like factor (from umbilical cord plasma) in human erythrocytes employing a 86Rb uptake assay. Increasing concentrations of canrenone (0-350 microM) partially competed with 3H-ouabain binding in placental membrane (40%) and erythrocytes (60%). Scatchard plot from radioreceptor assay in placental membrane showed that ouabain and canrenone compete for the same binding site. In erythrocytes, canrenone completely reversed the inhibition caused by ouabain (5 x 10(-9) M) and ouabain-like factor (2 x 10(-9) M ouabain equivalents). A reduction of inhibition of about 50% was observed with ouabain and ouabain-like factor respectively at a concentration of 5 x 10(-8) M and 2 x 10(-8) M (ouabain equivalents). Our results thus provide evidence that canrenone, at therapeutical concentrations, is a partial competitive agonist of ouabain and of ouabain-like factor in human placental membranes and erythrocytes.

Binding Sites↗
PubMed2002

Identification of a novel gp100/pMel17 peptide presented by HLA-A*6801 and recognized on human melanoma by cytolytic T cell clones.

Melanoma-associated peptides recognized by cytolytic T lymphocytes (CTL) in the context of several histocompatibility leukocyte antigens (HLA) are required for the development of specific immunotherapies. Using a transient transfection assay into COS-7 cells, we identified the gp100/pMel17 melanosomal protein as the shared antigen recognized by three independent CD8+ CTL clones in HLA-A*6801-restricted fashion. This finding was confirmed by the correlation between lack of gp100/pMel17 protein in a number of HLA-A*6801-positive melanomas and their resistance to lysis/cytokine production by the specific effectors. The gp100/pMel17 antigenic epitope was identified based on recognition of subfragments and on a computer-based prediction algorithm. Among a panel of gp100/pMel17-derived synthetic peptides only the 10-mer HTMEVTVYHR (gp100/pMel17182-191) induced tumor necrosis factor (TNF) release by CTL clones when pulsed on suitable target cells whereas both the 10-mer and the shorter 9-mer gp100/pMel17183-191 sensitized the same antigen-pulsed cells to lysis. In conclusion, the identification of the HTMEVTVYHR peptide will extend to HLA-A*6801 melanoma patients the possibility to exploit gp100/pMel17 melanosomal protein for experimental and clinical studies.

Amino Acid Sequence↗
PubMed2002

Fate of chronic myeloid leukemia patients treated with allogeneic bone marrow transplantation or chemotherapy and/or interferon at a single center: long-term results.

From April 1981 to February 2000, 105 patients with chronic myeloid leukemia (CML) underwent BMT from HLA-identical related donors at a single center. Eighty-eight patients were in chronic phase (CP), 11 patients in accelerated phase and six patients in blast crisis. Ten of these patients received a second BMT (BMT2). Comparison of BMT in CP with chemotherapy and/or alpha-IFN (n=70) was also made. Patients were given cyclophosphamide (CY) and single-dose TBI (CYTBI, n=38) or busulfan (BU) and CY (BUCY, n=67). Overall 54 patients are alive and 52 of them are disease-free with a median follow-up of 11.3 (range 1.1-19.4) years. Ten-year disease-free survival (DFS) in CP patients was better after BUCY, 61% (95% CI, 47-68%) than after CYTBI, 41% (95% CI, 23-61%) (P=0.07). For 88 patients who received a transplant in CP, results were significantly improved when BMT was performed within 1 year after diagnosis (P=0.02) or at an age < or = 25 years old (P=0.01). Ten-year survival in patients who received BMT in CP was better than in patients treated with chemotherapy (56% vs 10%; P=0.0001) or alpha-IFN-based treatment (33%; P=0.09) with survival curves crossing at 4.2 years and at 4 years, respectively. The probability of DFS after BMT2 was 60% (95% CI, 26-87%). CP patients who received BMT after CYTBI had a higher probability of relapse and transplant-related mortality than patients receiving BUCY (53% and 58% vs 9% and 34%; P=0.002 and P=0.08, respectively). All but six patients are currently on no medication and have resumed all activities without any limitation. These long-term results confirm that allogeneic BMT is the only curative approach for CML patients and should be offered to all patients with a suitable donor as soon after diagnosis as possible.

Adolescent↗
PubMed2002

Low-dose lansoprazole and clarithromycin plus metronidazole vs. full-dose lansoprazole and clarithromycin plus amoxicillin for eradication of Helicobacter pylori infection.

AIM: To compare, in a randomized controlled trial, the efficacy and tolerability of two 1-week triple therapies for Helicobacter pylori eradication. METHODS: One hundred and thirty-four consecutive patients with non-ulcer dyspepsia and H. pylori infection were randomized to receive lansoprazole 30 mg once daily, clarithromycin 250 mg twice daily, and metronidazole 500 mg twice daily (LCM group), or lansoprazole 30 mg twice daily, clarithromycin 500 mg twice daily, and amoxicillin 1000 mg twice daily (LCA group). H. pylori status was assessed by rapid urease test, histology and 13C-urea breath test before and after therapy. RESULTS: At 3 months, H. pylori eradication (intention- to-treat/per protocol analysis) was 92.4%/93.8% in the LCM group and 83.1%/85.7% in the LCA group (P=N.S.). Side-effects were more frequently reported in the LCA group (37.9%) than in the LCM group (19.7%) (P < 0.05). CONCLUSIONS: In this open, randomized controlled trial, eradication of H. pylori by low-dose lansoprazole and clarithromycin plus metronidazole was higher with significantly less side-effects than by full-dose lansoprazole and clarithromycin plus amoxicillin. This finding may be related to the stronger synergism of clarithromycin plus metronidazole, even at lower doses, than of clarithromycin plus amoxicillin. Considering the lower cost as well, LCM should be preferred to LCA in the eradication of H. pylori.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2002

Patient effective dose from endovascular brachytherapy with 192Ir sources.

The growing use of endovascular brachytherapy has been accompanied by the publication of a large number of studies in several fields, but few studies on patient dose have been found in the literature. Moreover, these studies were carried out on the basis of Monte Carlo simulation. The aim of the present study was to estimate the effective dose to the patient undergoing endovascular brachytherapy treatment with 112Ir sources, by means of experimental measurements. Two standard treatments were taken into account: an endovascular brachytherapy of the coronary artery corresponding to the activity x time product of 184 GBq.min and an endovascular brachytherapy of the renal artery (898 GBq.min). Experimental assessment was accomplished by thermoluminescence dosemeters positioned in more than 300 measurement points in a properly adapted Rqndo phantom. A method has been developed to estimate the mean organ doses for all tissues and organs concerned in order to calculate the effective dose associated with intravascular brachytherapy. The normalised organ doses resulting from cronary treatment were 2.4 x 10(-2) mSv.GBq(-1).min(-1) for lung, 0.9 x 10(-2) mSv.GBSq(-1).min(-1) for oesophagus and 0.48 x 10(-2) mS.GBq(-1).min(-1) for bone marrow. During brachytherapy of the renal artery, the corresponding normalised doses were 4.2 x 10(-2) mS.GBq(-1).min(-1) for colon, 7.8 x 10(-2) mSv.GBq(-1).min(-1) for stomach and 1.7 x 10(-2) mSv.GBq(-1).min(-1) for liver. Coronary treatment iJnvlled an efl'fective dose of (0.046 mSv.GBq(-1).min(-1), whereas the treatment of the renal artery resulted in an effective dose of 0.15 mSv.GBq(-1).min(-1); there were many similarities with data from former studies. Based on these results it can be concluded that the dose level of patients exposed during brachytherapy treatment is low.

Arteries↗