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Biomedical subjects

F Meloni

Publications and source records attributed to F Meloni.

At least 19 recordsLinked to original sources
PubMed2006

Peripheral CD4+ CD25+ Treg cell expansion in lung transplant recipients is not affected by calcineurin inhibitors.

CD4+CD25+ regulatory T (Treg) cells have been shown to play a role in allograft tolerance and their peripheral counts vary according to the degree of graft acceptance in lung transplant recipients (LTR). Recent studies demonstrate that certain drugs might modulate generation, expansion and activity of Treg cells. Aim of this study was to evaluate the effect of therapeutic regimens used in our institution on peripheral CD4+CD25(high)CD69- Treg cell numbers in a group of 51 LTR with stable clinical conditions. They were treated with standard immunosuppression: calcineurin inhibitor (CNI)+azathioprine (AZA)+steroids (n=28) or with CNI+mycophenolate mofetil (MMF)+steroids (n=11) or with CNI+steroids (n=12). These stable LTR were compared with age-matched healthy controls (n=35) and with 19 LTR who developed bronchiolitis obliterans syndrome (BOS) and were treated analogously. Stable LTR showed higher peripheral Treg cell counts with respect to age-matched healthy controls (59.9+/-31.8/mul versus 42.1+/-16.9/mul, respectively; p<0.05). This increase was detectable in all patients treated with CNI either in association with AZA or MMF. During these treatments a significant expansion of Treg cell counts was detectable during acute rejection (AR) episodes (86.03+/-26.6/mul during AR versus 36.34+/-7.6 before AR; p<0,05). Moreover, the development of BOS was associated to a significant decrease of Treg cell counts irrespective to the immunosuppressive regimen used. In conclusion, therapeutic regimens based on CNI seem to allow a certain degree of peripheral Treg cell expansion in stable LTR.

Adult↗
PubMed2006

Monitoring of human cytomegalovirus-specific CD4 and CD8 T-cell immunity in patients receiving solid organ transplantation.

Absolute and human cytomegalovirus (HCMV)-specific CD4+ and CD8+ T-cell counts were monitored in 38 solid organ (20 heart, 9 lung and 9 kidney) transplant recipients during the first year after transplantation by a novel assay based on T-cell stimulation with HCMV-infected autologous dendritic cells. According to the pattern of T-cell restoration occurring either within the first month after transplantation or later, patients were classified as either early (n = 21) or late responders (n = 17). HCMV-specific CD4+ and CD8+ T-cell counts were consistently lower in late compared to early responders from baseline through 6 months after transplantation. In addition, in late responders, while HCMV infection preceded immune restoration, HCMV-specific CD4+ restoration was significantly delayed with respect to CD8+ T-cell restoration. The number of HCMV-specific CD4+ and CD8+ T-cells detected prior to transplantation significantly correlated with time to T-cell immunity restoration, in that higher HCMV-specific T-cell counts predicted earlier immune restoration. Clinically, the great majority of early responders (18/21, 85.7%) underwent self-resolving HCMV infections (p = 0.004), whereas the great majority of late responders (13/17, 76.5%) were affected by HCMV infections requiring antiviral treatment (p = <0.0001). Simultaneous monitoring of HCMV infection and HCMV-specific T-cell immunity predicts T-cell-mediated control of HCMV infection.

Adult↗
PubMed2006

A double buccal fat pad flap for middle palate defect closure--a new technique for palate closure.

In this article a new method of closing palatal defects by means of buccal fat pad flaps is reported. A double buccal fat pad flap in association with Le Fort I osteotomy approach was adopted to remove tumours of the palate and nasal fossae. The technique is described in a case of adenocarcinoma arising from the nasal septum and its indications and advantages are discussed.

Adenocarcinoma↗
PubMed2006

Analysis of bronchoalveolar lavage fluid proteome from systemic sclerosis patients with or without functional, clinical and radiological signs of lung fibrosis.

Lung fibrosis is a major cause of mortality and morbidity in systemic sclerosis (SSc). However, its pathogenesis still needs to be elucidated. We examined whether the alteration of certain proteins in bronchoalveolar lavage fluid (BALF) might have a protective or a causative role in the lung fibrogenesis process. For this purpose we compared the BALF protein profile obtained from nine SSc patients with lung fibrosis (SScFib+) with that obtained from six SSc patients without pulmonary fibrosis (SScFib-) by two-dimensional gel electrophoresis (2-DE). Only spots and spot-trains that were consistently expressed in a different way in the two study groups were taken into consideration. In total, 47 spots and spot-trains, corresponding to 30 previously identified proteins in human BALF, showed no significant variation between SScFib+ patients and SScFib- patients, whereas 24 spots showed a reproducible significant variation in the two study groups. These latter spots corresponded to 11 proteins or protein fragments, including serum albumin fragments (13 spots), 5 previously recognized proteins (7 spots), and 4 proteins (3 spots) that had not been previously described in human BALF maps, namely calumenin, cytohesin-2, cystatin SN, and mitochondrial DNA topoisomerase 1 (mtDNA TOP1). Mass analysis did not determine one protein-spot. The two study groups revealed a significant difference in BALF protein composition. Whereas levels of glutathione S-transferase P (GSTP), Cu-Zn superoxide dismutase (SOD) and cystatin SN were downregulated in SScFib+ patients compared with SScFib- patients, we observed a significant upregulation of alpha1-acid glycoprotein, haptoglobin-alpha chain, calgranulin (Cal) B, cytohesin-2, calumenin, and mtDNA TOP1 in SScFib+ patients. Some of these proteins (GSTP, Cu-Zn SOD, and cystatin SN) seem to be involved in mechanisms that protect lungs against injury or inflammation, whereas others (Cal B, cytohesin-2, and calumenin) seem to be involved in mechanisms that drive lung fibrogenesis. Even if the 2-DE analysis of BALF did not provide an exhaustive identification of all BALF proteins, especially those of low molecular mass, it allows the identification of proteins that might have a role in lung fibrogenesis. Further longitudinal studies on larger cohorts of patients will be necessary to assess their usefulness as predictive markers of disease.

Bronchoalveolar Lavage Fluid↗
PubMed2005

Risk of tumour seeding after percutaneous radiofrequency ablation for hepatocellular carcinoma.

BACKGROUND: A recent small study reported a high rate of neoplastic seeding after cooled-tip radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) in patients who had undergone previous needle biopsy. Tumour seeding was associated with subcapsular tumour location, poorly differentiated tumours and a high alpha-fetoprotein (AFP) level. The aim of the present study was to determine the rate of neoplastic seeding after RFA in a large series of unselected patients with HCC who had a long follow-up. METHODS: A total of 1314 patients with 2542 nodules were treated in three centres. Median follow-up was 37 months. Needle biopsy had been performed before RFA in 241 patients (18.3 per cent). The influence of subcapsular location, high AFP level and previous biopsy on risk of tumour seeding was assessed. RESULTS: Neoplastic seeding was identified in 12 patients (0.9 per cent); the rate was comparable at the three centres (0.9, 0.7 and 1.4 per cent). Only previous biopsy was significantly associated with tumour seeding (P = 0.004). CONCLUSION: RFA with a cooled-tip needle was associated with a low risk of neoplastic seeding, even in unselected patients. The use of biopsy before RFA is to be discouraged, particularly when liver transplantation is a possibility at a later date.

Carcinoma, Hepatocellular↗
PubMed2005

The frequency of interleukin-10- and interleukin-5-secreting CD4+ T cells correlates to tolerance of transplanted lung.

Posttransplant bronchiolitis obliterans syndrome (BOS) results from a chronic immunological/inflammatory insult that leads to fibro-obliteration of the lumen of the allograft airways. The functional T-cell response that is associated with graft acceptance needs to be further clarified in humans. The aim of the present study was to assess the functional activity of peripheral CD4+ T lymphocytes in nine lung transplant recipients with BOS stage II or III (mean 5.4 years after transplant), in seven lung patients with stable clinical conditions (3.4 years posttransplant); and in six normal controls. Peripheral CD4+ T cells, obtained by magnetic bead vs negative purification, were studied using a computer-assisted enzyme-linked immunospot assay (ELISPOT) to assess the number of IFN-gamma-, interleukin (IL)5-, and IL10-gamma-producing cells (no./10(6) CD4+ cells) after allogeneic stimulation. The frequencies of IFN-gamma-producing CD4+ cells did not change significantly in stable patients compared to those with BOS. Interestingly in BOS, the number of IL5- and IL10-producing cells was significantly lower than in stable patients (P < or = .05), suggesting a possible role of these Th2 cytokines in the modulation of graft tolerance.

Adult↗
PubMed2005

Ex vivo evaluation of PPD-specific IFN-gamma or IL-5 secreting cells in the peripheral blood and lungs of patients with tuberculosis.

OBJECTIVES: To evaluate ex vivo purified protein derivative (PPD) specific Th1- and Th2-type functional responses in human tuberculosis (TB). DESIGN: IFN-gamma and IL-5 secreting cells were measured by a computer-assisted ELISPOT assay in the peripheral blood of patients with pulmonary TB, in patients with other respiratory diseases (control patients) and in tuberculin skin test negative or positive healthy controls. Moreover, the number of IFN-gamma or IL-5 spots was assessed in the bronchoalveolar lavage (BAL) cells of five patients with advanced TB and lung inflammation. RESULTS: The frequency of PPD-specific IFN-gamma secreting cells in TB patients was higher than in control patients and healthy subjects. Although the number of PPD-specific IL-5 spots was low, a trend towards a higher frequency was observed in the peripheral blood of TB patients. Patients with advanced TB and lung inflammation had an increased number of both PPD-specific IFN-gamma and IL-5 spots in BAL as compared to that in peripheral blood, but the IFN-gamma/IL-5 ratio was about two-fold lower. CONCLUSIONS: In human TB, the host response in the periphery is driven by a specific Th1-type cytokine response, whereas in the lungs of patients with advanced disease and lung inflammation, polarisation towards a Th2-like bias is observed.

Adult↗
PubMed2005

Cytomorphologic and ultrastructural study of nasal mucosa by means of brushing: a comparison between asymptomatic and rhinitic subjects.

The authors compared the cytomorphologic and ultrastructural features of nasal epithelium collected by means of brushing from asymptomatic subjects with these of patients affected by nasal polyposis (NP), allergic (AR) and non-allergic rhinitis (NAR). A brushing of nasal epithelium was taken from each member of both groups, and analysed under light and electron microscopy. The observation showed normal ciliary patterns and preserved intercellular joints in the great majority of asymptomatic subjects, while in all subjects of the pathologic group the junctions appeared variously damaged or absents, with ciliary abnormalities. The damage to the intercellular joints, rather than the alterations of ciliary patterns, seemed to represent in this study the border between the absence of symptoms and the presence of chronic inflammation. Therefore, a reduced tightness of the intercellular joints could contribute to the impairment of the mucociliary clearance, priming the vicious circle that leads to the condition of chronic inflammation.

Adult↗
PubMed2004

Acute Chlamydia pneumoniae and Mycoplasma pneumoniae infections in community-acquired pneumonia and exacerbations of COPD or asthma: therapeutic considerations.

Rates of acute Chlamydia pneumoniae and Mycoplasma pneumoniae infections were determined in 115 adults hospitalized for community-acquired pneumonia (CAP), purulent exacerbations of COPD and acute exacerbations of bronchial asthma, by means of serology and molecular methods. Results were compared with those obtained in a matched control group. Common respiratory pathogens were isolated by cultures in 22.5% and 22.2% of CAP and exacerbated COPD patients, respectively. Cultures from exacerbated asthma patients were always negative. Serological and molecular evidence of current C. pneumoniae infection was obtained in 10.0%, 8.9% and 3.3% of CAP, COPD and asthma cases. The corresponding rates of acute M. pneumoniae infection were 17.5%, 6.7% and 3.3%, respectively. Finally, no difference was found between typical and atypical pathogen rates. These findings highlight the importance of taking into account C. pneumoniae and M. pneumoniae infections in guiding the choice of empirical antibacterial treatment for CAP and purulent exacerbations of COPD.

Acute Disease↗
PubMed2003

Monocyte chemoattractant protein-1 levels in bronchoalveolar lavage fluid of lung-transplanted patients treated with tacrolimus as rescue treatment for refractory acute rejection.

BACKGROUND: Cytokines are important mediators of the complex process of extravasation and influx of peripheral mononuclear cells into a site of graft injury, an action that may be affected by the immunosuppressive regimen. The aim of this study was to compare the effect of different immunosuppressive regimens on cytokine expression in the grafted lung. METHODS: We analyzed the cytokine profiles in broncho-alveolar lavage fluid (BAL-F) from 18 lung transplanted patients undergoing a shift from a cyclosporine- to a tacrolimus-based triple therapy regimen due to refractory acute rejection. RESULTS: Three months after the conversion to tacrolimus, BAL-F levels of interleukin 8 (IL8), IL18, IL12 and IL10 were not significantly different than those measured before conversion. In contrast, monocyte chemoattractant protein-1 (MCP-1) levels showed a significant and sustained decrease in BAL-F during tacrolimus therapy. In addition the levels of gamma interferon (IFN-gamma) in the BAL-F were decreased albeit not significantly. CONCLUSIONS: These findings suggest that the clinical and functional stabilization of patients observed after conversion to a tacrolimus based regimen, may be due, at least in part, to the induced down-regulation of MCP-1 production.

Acute Disease↗
PubMed2003

The assessment of IFN-gamma and its regulatory cytokines in the plasma and bronchoalveolar lavage fluid of patients with active pulmonary tuberculosis.

OBJECTIVES: To assess the role of IFN-gamma and its regulatory cytokines in active pulmonary tuberculosis (TB). DESIGN: Cytokines were measured in the plasma of TB patients and healthy subjects with different risk for TB exposure. In addition, cytokine profile was assessed in the bronchoalveolar lavage fluid (BALf) of six TB patients and nine normal controls. RESULTS: Circulating IFN-gamma, IL-10 and IL-18 were higher in TB patients than in control groups. Plasma IL-12 levels were extremely variable, and no difference was observed among study groups. An inverse correlation between plasma IFN-gamma and IL-10 levels was found in TB patients. Furthermore, circulating IL-18 correlated with IL-10 but not with IFN-gamma levels. Finally, IFN-gamma, IL-18 and IL-12 were increased in the BALf of TB patients, whereas no difference was observed in IL-10 levels. CONCLUSIONS: In human TB, at least at certain disease stages, there is a differential compartmentalization of the IFN-gamma-regulatory factors IL-12 and IL-10, the former being concentrated in the lungs and the latter being present in peripheral circulation. In addition, our findings address more critically the role of IL-18 in the host response to tuberculosis infection in humans.

Adult↗
PubMed2002

A 10-year survey of Mycobacterium tuberculosis isolates in Pavia and their drug resistance: a comparison with other Italian reports.

A retrospective review was made of the bacteriological and medical records of patients with culture-confirmed pulmonary tuberculosis who attended the IRCCS San Matteo Polyclinic of Pavia, between 1990 and 2000. Altogether, 279 patients were included in the survey: 220 new cases and 59 prior treatment cases. Resistance to at least one drug, and resistance to both isoniazid and rifampicin (MDR) were more common among previously treated patients than among new cases (86.4% vs. 34.1%, and 44% vs. 5.9%, respectively). While the frequency of resistance to any drug showed no variation in the period examined, a trend toward a progressive decrease in the frequency of primary MDR-TB was observed (from 11.9% in 1990-1992 to 1.3% in 1998-2000). The level of resistance observed in our study suggests that all isolates of Mycobacterium tuberculosis should be tested for drug susceptibility, especially when obtained from patients who report a previous episode of the disease.

Drug Resistance, Multiple, Bacterial↗
PubMed2002

Surfactant apoprotein A modulates interleukin-8 and monocyte chemotactic peptide-1 production.

Previous studies have shown that surfactant apoprotein A (SP-A) and natural or synthetic surfactant can modulate the release of pro-inflammatory cytokines from alveolar mononuclear phagocytes. The aim of this study was to assess whether SP-A or Surfactant (Surf) from patients with pulmonary alveolar proteinosis (PAP) can affect the release of two chemokines (interleukin (IL)-8 and monocyte chemtactic peptide (MCP)-1) from human monocytes and rat lung type-II cells. In addition IL-8 and MCP-1 levels were assessed in the brochoalveolar lavage fluid (BALF) of seven patients with PAP and compared with those in a group of control subjects (n=5). SP-A, tested over a wide range of concentrations, significantly increased IL-8 and MCP-1 release from monocytes. SP-A retained its activity after collagenase digestion, but was not active after heat treatment. The release of IL-8 by monocytes was also stimulated by Surf. Finally, median BALF IL-8 and MCP-1 levels in PAP patients were significantly higher than in controls (9.50 and 9.51 pg x mL(-1) in controls versus 151.95 and 563.70 pg x mL(-1) in PAP, respectively) and significantly correlated with SP-A concentrations in BALF. Overall the results of this study support the view that the high content of alveolar surfactant apoprotein A may contribute to the upregulation of chemokine release in pulmonary alveolar proteinosis, thus contributing to airway inflammation.

Adult↗
PubMed2001

Percutaneous ethanol injection: single session treatment.

OBJECTIVE: Percutaneous ethanol injection (PEI) has become one of the most widely used procedures for treating hepatocellular carcinoma (HCC) in patients with cirrhosis. PEI spread rapidly thanks to its ease of execution, safety, low resection cost, repeatability, therapeutic efficacy, and survival rates comparable to those of surgical resection. A new version of the procedure known as "single session" PEI, designed for treatment of large HCC under general anesthesia, was proposed in 1993. MATERIALS AND METHODS: In our study of 108 patients with HCC>5 cm in diameter, 24 patients (Group A), were treated for a single and encapsulated lesions measuring from 5-8.5 cm, 63 patients (Group B), had a single and infiltrating lesions measuring from 5-10 cm or multiple HCC; and 21 patients (Group C), had advanced disease. RESULTS: In Group A, complete necrosis was achieved in 58.3% of lesions, in Group B complete necrosis was achieved only in encapsulated lesions. In infiltrating lesions of Group B and C, complete necrosis was never obtained. Survival of patients at 3 years with encapsulated HCC was 57%, in infiltrating or multiple HCC 42%, and in advanced HCC 0%. One death due to bleeding of esophageal varices occurred in a Child's C patient. Major complications included intraperitoneal hemorrhage, an important hepatic decompensation, a transitory renal insufficiency, and two infarction of adiacent segment. CONCLUSION: Single session PEI is as effective in inducing liver tumor necrosis as traditional PEI. Its advantage are shorter treatment time and the capability of treating larger and multiple HCC. The One-shot technique proved a more aggressive therapeutic modality than traditional PEI.

Carcinoma, Hepatocellular↗
PubMed2001

Radiofrequency thermal ablation of hepatocellular carcinoma.

Radiofrequency (RF) ablation resulted in a higher complete necrosis than percutaneous ethanol injection (PEI), above all in infiltrating lesions, and requires fewer treatment sessions in the treatment of small size tumors. We achieved 90% of complete necrosis in hepatocellular carcinoma (HCC)<3 cm, 71% in medium (3-5 cm) and 45% in large (5.1-9 cm) HCC. However, near complete necrosis was obtained in the majority of the remaining tumors. PEI is preferable in lesions at risk with RF, i.e. adjacent to main biliary ducts or to intestinal loops. Our current 3-yr survival in child A patient with single HCC<5 cm is 85%.

Animals↗
PubMed2001

Increased concentrations of inflammatory mediators in unstable angina: correlation with serum troponin T.

OBJECTIVE: To measure plasma interferon gamma, monocyte chemotactic protein-1 (MCP-1), and interleukin 6 and to assess their correlation with cardiac troponin T in unstable angina. DESIGN: Blood sampling in patients undergoing coronary arteriography for known or suspected ischaemic heart disease. PATIENTS: 76 patients divided in three groups: 29 with unstable angina (group 1), 28 with stable angina (group 2), and 19 without ischaemic heart disease and with angiographically normal coronary arteries (group 3). MAIN OUTCOME MEASURES: Plasma interleukin 6, interferon gamma, MCP-1, and troponin T in the three groups of patients. RESULTS: Interleukin 6 was increased in group 1 (median 2.19 (range 0.53-50.84) pg/ml) compared with the control group (1.62 (0.79-3.98) pg/ml) (p < 0.005), whereas interferon gamma was higher in group 1 (range 0-5.51 pg/ml) than in the other two groups (range 0-0.74 pg/ml and 0-0.37 pg/ml; p < 0.005 and p < 0.001, respectively). Patients with unstable angina (group 1) and positive troponin T had higher concentrations of interferon gamma than those with negative troponin T (0-5.51 pg/ml v 0-0.60 pg/ml, p < 0.001). Plasma MCP-1 was also higher in group 1 (median 267 (range 6-8670) pg/ml) than in the other two groups (134 (19-890) pg/ml and 84.5 (5-325) pg/ml; p < 0.005 and p < 0.001, respectively), and among group 1 patients with a positive troponin T assay than in those with normal troponin T (531 (14.5-8670) pg/ml v 69 (6-3333) pg/ml; p < 0.01). There was no difference in plasma interleukin 6 in group 1 patients between those with and without raised troponin T. CONCLUSIONS: The inflammatory cytokines interferon gamma and MCP-1 are increased in patients with unstable angina, particularly in those with raised concentrations of troponin T, suggesting that they are probably related to myocardial cell damage or to plaque rupture and thrombus formation.

Adult↗