Search PubMed⌕ Search

Biomedical subjects

G Segoloni

Publications and source records attributed to G Segoloni.

At least 19 recordsLinked to original sources
PubMed2005

A randomized trial of steroid avoidance in renal transplant patients treated with everolimus and cyclosporine.

In this randomized trial renal transplant recipients were treated with basiliximab, everolimus 3 mg/day, low-dose CsA. At transplantation, patients were randomized to stop steroids at the seventh day (group A) or to continue oral steroids in low doses (group B). Of the 113 patients enrolled, 65 were randomized to group A and 68 to group B. All patients were followed for 2 years. During the study 28 (43%) group A patients required reintroduced corticosteroids. One patient died, in group B. The Graft survival rate was 97% in group A and 90% in group B. There were more biopsy-proven rejections in group A (32% vs 16%; P = .044). The mean creatinine clearance was 54 +/- 21 mL/min in group A vs 56 +/- 22 mL/min in group B. Mean levels of serum cholesterol tended to be lower in group A, but the difference was of borderline significance (191 +/- 91 vs 251 +/- 188 mg/dL; P = .07). Vascular thrombosis (0 vs 5) and pneumonia requiring hospitalization (2 vs 7) tended to be more frequent in group B. Only three cases of CMV infection (1 vs 2) occurred. An immunosuppressive therapy with everolimus and low-dose CsA allows one to obtain excellent renal graft survival and stable graft function at 2 years. Early interruption of steroids in patients treated with this regimen may increase the risk of acute rejection, but neither affects graft survival nor graft function, while possibly reducing the risk of hyperlipemia and vascular thrombosis. About 60% of patients given everolimus and low-dose CsA can definitively stop steroids after 1 week.

Adolescent↗
PubMed2005

Blood cyclosporine level soon after kidney transplantation is a major determinant of rejection: insights from the Mycophenolate Steroid-Sparing Trial.

Target organs express antigens directly recognized by antigen-specific T cells, thereby precipitating rejection. When early T-cell activation is inhibited, there is a low risk of rejection. We sought to determine the predictive values of serial posttransplant blood cyclosporine trough (C(0)) concentrations to minimize the risk for a first rejection episode compared with 2-hour postdose (C(2)) drug concentrations. The final aim of the study was to identify a concentration range for the best predictive pharmacokinetic parameter that should be targeted to reduce the risk of rejection. This possibility was explored in 334 de novo kidney transplant recipients who participated in the prospective, multicenter Mycophenolate Steroid-Sparing Trial. Among measurements performed during the first 6 months postsurgery, cyclosporine C(0) levels measured early after transplantation were the strongest predictor of acute graft rejection. Levels within 300 to 440 ng/mL were associated with the lowest risk of rejection, while patients with levels lower than 300 ng/mL showed a more than double risk. Cyclosporine trough values predicted allograft rejection with an accuracy of 74%, while C(2) levels had no predictive value. These findings underline the need to target cyclosporine therapy early posttransplant to modulate T-cell activation.

Adrenal Cortex Hormones↗
PubMed2003

Comparison between a two-drug regimen with tacrolimus and steroids and a triple one with azathioprine in kidney transplantation: results of a European trial with 3-year follow up.

This study was designed to assess the efficacy and safety of two immunosuppressant regimens in kidney transplantation based on the administration of tacrolimus-one of them with tacrolimus, azathioprine, and corticosteroids (n=239) and the other with tacrolimus, and corticosteroids (n=236). After completing the initial 3-month study, the patients remaining in the study (197 and 195, respectively) were assessed for 3 years. The incidence of acute rejection (AR) episodes treated during this period was 28.8% with dual-drug therapy and 29.7% with triple-drug therapy. Late AR: episodes between 4 and 36 months were scarce (3.3% in dual and 4.2% in triple therapy). Chronic rejection incidence was 7.7% and 8.9%, respectively. The patients who experienced AR episodes during the first 3 months developed chronic rejection more frequently than those who did not suffer AR. Patient survival at 3 years was 95% vs 95.6%, and graft survival was 86.6% vs 86.5% (NS). Doses and blood levels of tacrolimus were similar in the two groups. Adverse effects were similar among both treatment groups. Median SCr was 123.8 micromol/L vs 114.9 micromol/L in patients who did experience AR: 145.9 micromol/L vs 132.6 micromol/L in those with early AR; and 194.5 micromol/L vs 152 micromol/L in those who presented with late AR. Need for de novo posttransplant insulin was 4.2% in the dual-drug group and 3.8% in the triple-drug cohort. These results demonstrate that, after 3 years of follow up, there were similar efficacy data among the dual- and triple-drug regimens. Thus, addition of azathioprine does not contribute any advantage in the middle term.

Acute Disease↗
PubMed2001

Daily dialysis Kt/V and flexible schedules: is it possible to control efficiency, when and how?

BACKGROUND: Daily hemodialysis is a promising treatment schedule but uniform criteria for defining efficiency are lacking. METHODS: On our daily dialysis (DD) schedule, duration is flexible (2-3 hours, patients are free to add up to 30 min/session), Qb 250-350 mL/min; dialyser 1.6-1.8 m2. Study was performed on 12 pts on DD for > or = 2 months, with > or = 4 Kt/V on subsequent days, tested in the same laboratory. GOAL: To evaluate variability and identify a simple method for weekly calculation, Kt/V was assessed for 133 sessions. RESULTS: On flexible DD, variability of Kt/V-session is high (relative error 4.9%-22%). On flexible schedules, within the time range chosen (2-3 hours) variability of average hourly Kt/V is lower (standard deviation: min (0.014; max (0.052 hour, relative error 4.9%-10%) allowing calculation of weekly Kt/V (averaging 3 sessions: relative error < 6%) suitable for clinical practice. CONCLUSIONS: Flexible schedules, allowing patients to increase treatment time, are an interesting clinical option, but a challenge for Kt/V assessment.

Adult↗
PubMed2000

Role of platelet-activating factor in functional alterations induced by xenoreactive antibodies in porcine endothelial cells.

BACKGROUND: Platelet-activating factor (PAF) is a phospholipid mediator of inflammation which has been implicated in rejection. The interaction of anti-alpha-galactosyl natural antibodies (anti-alpha gal Abs) with endothelial cells is the initial step for the development of xenograft rejection. In our study, we stimulated porcine aortic endothelial cells (PAEC) with anti-alpha gal IgG to investigate the synthesis of PAF from PAEC and its biological consequences. METHODS AND RESULTS: PAF was extracted and chromatographically purified from cultured PAEC stimulated with baboon anti-alpha gal Abs. The Abs induced a dose-dependent synthesis of PAF peaking after 30 min of incubation, and decreasing thereafter. Concomitant cell shape change, motility, and cytoskeleton redistribution were observed. These events were prevented by addition of a panel of PAF-receptor antagonists. An SV40 T-large antigen-immortalized PAEC line was engineered to express PAF acetyl-hydrolase (PAF-AH) cDNA, the major PAF-inactivating enzyme. These transfected cells exposed to anti-alpha gal Abs showed reduced cell contraction and motility compared with empty vector-transfected cells. Moreover, in PAEC stimulated with anti-alpha gal Abs, the synthesis of PAF promoted the adhesion of a monocytic cell line as shown by the inhibitory effect of PAF-receptor antagonists and of PAF-AH expression. Finally, studies on cell monolayer demonstrated an enhanced permeability 48 hr after exposure to anti-alpha gal Abs, and this increase was prevented by PAF-inactivation and by PAF-receptor blockade. CONCLUSIONS: These results demonstrate that on stimulation with anti-alpha gal Abs, PAEC synthetize PAF which can contribute to several vascular events involved in xenograft rejection.

Animals↗
PubMed2000

Tacrolimus is highly effective in both dual and triple therapy regimens following renal transplantation. Spanish and Italian Tacrolimus Study Group.

This open, multicenter, randomized, parallel-group study evaluated the efficacy and safety of tacrolimus-based dual and triple therapy regimens. For this 3-month study (with 12-month follow up), 491 adult renal transplant patients were randomized and received either dual therapy (tacrolimus/corticosteroids; 246 patients) or triple therapy (tacrolimus/corticosteroids/azathioprine; 245 patients). Patient survival rates at months 3 and 12 were 99.2 (dual) vs 99.6% (triple) and 97.8 vs 98.7%, respectively. Graft survival rates at months 3 and 12 were 94.1 (dual) vs 95.4% (triple) and 92.8 vs 93.3%, respectively. After 3 months, the incidences of treated acute rejection were 28.8 (dual) and 29.7% (triple); and 7.6 (dual) and 5.4% (triple) for corticosteroid-resistant acute rejections. Between months 4 and 12, three new first rejections were reported, (dual: 2, triple: 1). For leukopenia (1.3 vs 11.7%; P < 0.001) and anemia (14.8 vs 23.0%, P = 0.026), significantly higher incidences were reported in the triple therapy group. The incidence of de novo insulin-dependent diabetes was 5.6 (dual) and 4.0% (triple) at month 3. In terms of efficacy, no difference between the treatment groups was observed.

Acute Disease↗
PubMed1998

Expression of inducible lymphocyte costimulatory molecules in human renal allograft.

BACKGROUND: CTLA-4/CD28-B7 and CD40-CD40L interactions constitute two key costimulatory pathways in lymphocyte signalling during experimental allograft rejection. Studies on the expression of these molecules in human transplant rejection are still lacking. METHODS: The immunohistochemical study was performed on renal biopsies obtained for various clinical complications from 25 renal transplant patients. Expression of B7-1 and B7-2 and their counter-receptor CTLA-4, and of CD40 and its counter-receptor CD40L was examined. RESULTS: In acute rejection a focal intense infiltration of B7-1+ and B7-2+ cells (mainly CD20- CD14+) and of CTLA-4+ T lymphocytes (mainly CD8+) was present. In contrast, CD40 and CD40L were rarely expressed. Accumulations of T lymphocytes were found in the interstitium in the same area containing B7-1+ and B7-2+ cells. The scattered CD40L+ cells found in the T-cell infiltrate exhibited the CD4+ phenotype. In chronic rejection only a few B7-1+, B7-2+ or CTLA-4+ cells were detectable. In contrast, several CD40L+CD4+ cells were present both in the interstitium and in glomeruli. Moreover, an intense expression of CD40 on the endothelium was observed. In patients with cyclosporin nephrotoxicity cells positive for B7-1, B7 2, CTLA-4, CD40, or CD40L were absent. CONCLUSIONS: These results demonstrate a differential expression of costimulatory molecules in renal biopsies of allograft recipients undergoing acute or chronic rejection. Moreover, their detection may prove useful to discriminate rejection from cyclosporin nephrotoxicity.

Abatacept↗
PubMed1997

The modulatory effect of diltiazem on human in vitro alloreactivity when used alone or in combination with cyclosporin A and/or methylprednisolone.

The calcium channel blocker diltiazem is often included in post-transplant regimens in combination with other immunosuppressive drugs such as cyclosporin A (CyA). It is primarily used because of its antinephrotoxic and antihypertensive effects, so that undesirable side effects induced by the immunosuppressive therapy can be reduced. Its alleged ability to induce direct immunosuppression may explain the encouraging results from its clinical use and would appear to encourage a much wider use of this drug. The present study shows the effect of diltiazem on the human in vitro alloresponse when used alone or in combination with cyclosporin A (CyA) and methylprednisolone (MP). The results show that, when administered alone, diltiazem exerts a suppressive effect, but only at high, non-therapeutic doses. Interestingly, in combination with CyA or MP, diltiazem enhances the suppressive effect of these two drugs on in vitro alloresponses at lower doses. This additional effect of diltiazem may contribute to better graft survival in clinical transplantation.

Adjuvants, Immunologic↗
PubMed1996

[Epstein-Barr virus infection and lymphoproliferative disorders in patients after renal transplantation].

We have studied EBV infection in renal transplant patients during the first year after transplantation. At trasplantation all patients were EBV seropositive and reactivation of EBV infection was demonstrated in 54% cases after one year. CMV active infection was also demonstrated in 42% of patients with EBV reactivation. No correlation was observed between EBV reactivation and age, sex, immunosuppressive treatment, degree of immunosuppression or donor/recipient HLA matching. A correlation between immunosuppressive treatment, EBV infection and lymphoproliferative disorders (LD) is described in literature, however none of our patients developed LD so far, probably due to the different immunosuppressive protocol employed.

Adult↗
PubMed1995

IgA serology in recurrent and non-recurrent IgA nephropathy after renal transplantation.

BACKGROUND: This study investigated whether abnormal circulation of macromolecular IgA and IgA with altered glycosylation or electrical charge plays a role in the recurrence of IgA nephropathy (IgAN) after transplantation. STUDY DESIGN: A total of 92 renal transplant patients were enrolled; 52 IgAN patients and 40 with other non-IgAN. The IgAN group included 10 patients showing IgA mesangial deposits in the grafted kidneys (recurrent group) and 10 who did not (immunohistochemically proven non-recurrent group). In addition another 22 IgAN transplant patients were clinically free of recurrent disease. METHODS: The analyses included macromolecular IgA (IgAIC) detected by the conglutinin assay (K), heavy IgA precipitated in 2.5% polyethylene glycol (PEG), IgA-fibronectin aggregates (IgA/F Aggr), mixed IgA/IgGIC, IgA binding to mesangial matrix components (fibronectin, laminin, type IV collagen) or polycations (poly-L-lysine) and IgA with altered glycosylation (Jacalin-binding assay). RESULTS: After transplantation, IgAN patients displayed significantly higher mean levels for each variable measured than non-IgAN (ANOVA, P < 0.05). By stepwise regression analysis, the binding of IgA to fibronectin had the highest coefficient. By comparing data in recurrent and clinically non-recurrent IgAN, we observed that two groups could be distinguished by the results of the two assays for macromolecular IgA (conglutinin IgAIC and IgA-fibronectin aggregates) and IgA with increased affinity for type IV collagen (P < 0.05). When the selected group of immunohistochemically proven non-recurrent IgAN was compared to the recurrent one, a statistically significant difference was found only for the binding of IgA to type IV collagen (P < 0.05). Data from this test were significantly related with proteinuria (P < 0.05) and microscopic haematuria (P < 0.04). CONCLUSIONS: Even though the IgA serology of renal transplant IgAN patients shows peculiar features and recurrent and non-recurrent IgAN differ in many aspects, the prevalence of positive data in the two groups had no predictive value. This suggests that the recurrence of IgAN is modulated by factors affecting the interaction between circulating abnormal IgA and mesangial cells and/or matrix.

Analysis of Variance↗
PubMed1994

Long-term outcome in continuous ambulatory peritoneal dialysis: a 10-year-survey by the Italian Cooperative Peritoneal Dialysis Study Group.

Over a 10-year period, 1,990 end-stage renal disease patients in 30 centers were treated with continuous ambulatory peritoneal dialysis by the Italian Cooperative Peritoneal Dialysis Study Group. At the start of treatment, patients had an average age of 58.4 years, with a 66% prevalence of one or more clinical risk factors for premature death. Patient survival was 51% and 33% at 4 and 8 years on continuous ambulatory peritoneal dialysis, respectively, and technique survival was 62% and 48%, respectively. Occurrences of peritonitis progressively reduced until they reached an incidence of 0.50 episodes/yr in the last 5 years (1985 to 1989). Hernias and catheter-related problems did not influence the dropout rates. These Italian Cooperative Peritoneal Dialysis Study Group results demonstrate that continuous ambulatory peritoneal dialysis is a viable dialysis technique for long-term treatment of chronic renal failure and that it is an effective alternative to hemodialysis, especially for older and high-risk patients.

Adolescent↗
PubMed1993

Membranous glomerulonephritis (MGN) in transplanted kidneys: morphologic investigation on 256 renal allografts.

Twenty-two cases of membraneous glomerulonephritis (MGN) were identified among 256 bioptically investigated transplanted patients. MGN was defined as de novo in 15 patients and recurrent in three. The type of MGN could not be ascertained with certainty in the other four. Several morphologic features unusual for the idiopathic form of MGN were found. Most cases disclosed focal segmental distribution of subepithelial deposits and showed the contemporaneous presence of different stages of the disease according to Ehrenreich and Churg classification. In addition mild-to-moderate mesangial cell proliferation was found in about one third of de novo MGN biopsies. Endocapillary hypercellularity was observed in 14 specimens and held to be due to an excess of mononuclear blood cells, related to a concomitant episode of rejection. Chronic transplant glomerulopathy was found in 47% of patients with de novo MGN and in 66% of those with recurrent MGN, being more frequently observed in specimens with diffuse distribution of deposits. Repeated biopsies showed progression of the stage and extension of deposits to a large number of capillary loops in four out of six patients. De novo MGN was documented 1 to 54 mo (mean value 20.2 mo) after transplantation, and the recurrence was observed after 12, 15, and 42 mo. All but two patients (who were anuric) complained of proteinuria, which was in the nephrotic range in 12. Apart from the significantly higher frequency in de novo MGN patients of DR4 antigen, whose significance must in any case be re-evaluated in a larger series, none of the factors so far suggested to be linked to the onset of de novo MGN has found further support in our study. On the contrary, relevance in favoring the appearance and the evolution of MGN has to be attributed to transplant glomerulopathy, which, moreover, seems to be more important than MGN itself in causing the unfavorable outcome of the graft.

Adult↗
PubMed1992

Production of tumor necrosis factor-alpha in patients on hemodiafiltration.

The systemic production of tumor necrosis factor (TNF)-alpha was evaluated in uremic patients before and after hemodiafiltration (HDF) and paired filtration dialysis (PFD) and in the interdialytic period. Both HDF and PFD were performed using polysulfone dialyzers with either standard or ultrapure dialysis fluid. TNF-alpha was quantitated by using a specific biological assay based on its cytotoxic effect on a TNF-sensitive human melanoma cell line SK-MEL-109. Postdialytic mean plasma TNF-alpha levels decreased, albeit not significantly, in regard to predialytic values. These results differ from those obtained in patients on HDF using other high-permeability membranes such as polymethylmethacrylate and polyacrylonitrile (AN 69) as recently described by us. Of interest, the adoption of ultrapure dialysis fluid resulted in a marked reduction in the interdialytic production of TNF-alpha. These results suggest that the enhanced production of TNF-alpha in patients dialyzed with high-permeability membranes is mainly dependent upon the bacteriological purity of dialysis fluid.

Adult↗
PubMed1992

Comparison of survival in CAPD and hemodialysis: a multicenter study.

We studied 1,622 patients who started regular dialysis treatment between 1985 and 1989 in 19 centers from the Italian CAPD Study Group. There were 962 pts (59%) and on HD; 660 pts (41%) on CAPD. CAPD pts were older and had more risk factors at the start than HD pts (p < 0.0001). Overall patient survival was not statistically different between CAPD and HD at 6 years (42% CAPD; 54% HD). Multivariate analysis (Cox's model) on all population revealed that age and pretreatment risk factors had a statistically significant impact on patient survival (p < 0.0001), but not the type of dialytic treatment (CAPD or HD). When multivariate analysis was applied separately by treatment modalities, in HD group age and risk factors had the same negative influence on survival (p < 0.0001) while in CAPD group the influence of age on survival was less significant (p 0.025). This multicenter study carried out with appropriate statistical methods in a large number of pts demonstrates that patients' survival at 6 years is not different on CAPD and HD (despite the worse patient selection on CAPD) and can be even better on CAPD for aged patients.

Adult↗