Home About us Contact
|
Home About us Contact | ||
|
|
||
Antibody Induction (antibody + induction)
Selected AbstractsFixed- or Controlled-Dose Mycophenolate Mofetil with Standard- or Reduced-Dose Calcineurin Inhibitors: The Opticept TrialAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2009R. S. Gaston Mycophenolate mofetil (MMF) was developed with cyclosporine as a fixed-dose immunosuppressant. More recent data indicate a relationship between mycophenolic acid (MPA) exposure in individuals and clinical endpoints of rejection and toxicity. This 2-year, open-label, randomized, multicenter trial compared the efficacy and safety of concentration-controlled MMF (MMFCC) dosing with a fixed-dose regimen in 720 kidney recipients. Patients received either (A) MMFCC and reduced-level calcineurin inhibitor (MMFCC/CNIRL); (B) MMFCC and standard-level CNI (MMFCC/CNISL); or (C) fixed-dose MMF and CNISL (MMFFD/CNISL). Antibody induction and steroid use were according to center practice. The primary endpoint was noninferiority (,= 0.05) of group A versus group C for treatment failure (including biopsy-proven acute rejection [BPAR], graft loss and death) at 1 year. Although mean CNI trough levels in group A did not reach the prespecified targets, they were statistically lower than those in groups B and C (p , 0.01 for each comparison). BPAR rates (8.5%) were low across groups. Group A had 19% fewer treatment failures (23% vs. 28%, p = 0.18). MMF doses were highest (p < 0.05), with withdrawals for adverse events the fewest (p = 0.02), in group A. Of the 80% of subjects taking tacrolimus (Tac), those with higher MPA exposure had significantly less rejection (p < 0.001) and diarrhea correlated with Tac, but not with MPA levels. Thus, MMFCC with low-dose CNI resulted in outcomes not inferior to those with standard CNI exposure and MMFFD, indicating potential utility of MMFCC in CNI-sparing regimens. [source] Botulinum toxin A for palmar hyperhidrosisJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 6 2001U Wollina Abstract Objective We evaluated the efficacy and safety of intracutaneous injections of botulinum toxin A on severe palmar hyperhidrosis. Methods Ten patients with recalcitrant palmar hyperhidrosis were treated with intercutaneous injections of botulinum toxin A (Botox; 200 U for each hand). Patients were followed up to 23 months (mean ± SD: 12.1 ± 6.2 months). Results Botulinum toxin significantly reduced abnormal sweating within 1 week in 100% of the patients. In six patients with a follow-up of 12 months or more the antisudorific effect lasted 12.3 ± 5.5 months. The longest response duration was 22 months. Repeated treatment was performed in five patients with unchanged clinical efficacy. The only side-effect was tolerable pain from the intracutaneous injections in patients where a nerve block was not performed. Conclusions Botulinum toxin A (200 U Botox per palm) was able to induce long-term remission in palmar hyperhidrosis without significant acute and long-term side-effects. Strictly intracutaneous injection of small volumes is recommended. So far, response to repeated treatments did not show evidence of neutralizing antibody induction. [source] Long-term outcome of intensive initial immunosuppression protocol in pediatric deceased donor renal transplantationPEDIATRIC TRANSPLANTATION, Issue 1 2010Oyedolamu K. Olaitan Olaitan OK, Zimmermann JA, Shields WP, Rodriguez-Navas G, Awan A, Mohan P, Little DM, Hickey DP. Long-term outcome of intensive initial immunosuppression protocol in pediatric deceased donor renal transplantation. Pediatr Transplantation 2010: 14: 87,92. © 2009 John Wiley & Sons A/S. Abstract:, To report the long-term outcome of deceased donor kidney transplantation in children with emphasis on the use of an intensive initial immunosuppression protocol using R-ATG as antibody induction. Between January 1991 and December 1997, 82 deceased donor kidney transplantations were performed in 75 pediatric recipients. Mean recipient age at transplantation was 12.9 yr and the mean follow-up period was 12.6 yr. All patients received quadruple immunosuppression with steroid, cyclosporine, azathioprine, and antibody induction using R-ATG-Fresenius®. Actual one, five, and 10 yr patient survival rates were 99%, 97%, and 94%, respectively; only one patient (1.2%) developed PTLD. Actual one, five, and 10 yr overall graft survival rates were 84%, 71%, and 50%, respectively; there were five cases (6%) of graft thrombosis and the actual immunological graft survival rates were 91%, 78%, and 63% at one, five, and 10 yr, respectively. The use of an intensive initial immunosuppression protocol with R-ATG as antibody induction is safe and effective in pediatric recipients of deceased donor kidneys with excellent immunological graft survival without an increase in PTLD or other neoplasms over a minimum 10-yr follow up. [source] Mycophenolate mofetil without antibody induction in cadaver vs. living donor pediatric renal transplantationPEDIATRIC TRANSPLANTATION, Issue 2 2003O. Ojogho Abstract: Mycophenolate mofetil (MMF) is a new immunosuppressive agent that blocks de novo purine synthesis in T and B lymphocytes via a potent selective inhibition of inosine monophosphate dehydrogenase. MMF has been shown to significantly reduce the incidence of acute rejection in both adult and pediatric renal transplantation. The impact of MMF on routine antibody induction therapy in pediatric renal transplantation has not been defined. Remarkably, a recent North American Pediatric Transplant Cooperative Study concluded that T-cell antibody induction therapy was deleterious for patients who received MMF. Our study examines the use of MMF in an evolving immunosuppressive strategy to avoid antibody induction in both living (LD) and cadaver (CAD) donor pediatric renal transplantation. We retrospectively analyzed the records of 43 pediatric renal transplants that received MMF-based triple therapy without antibody induction therapy between November 1996 and April 2000. We compared CAD (n = 17) with LD (n = 26). The two groups were similar demographically except that CAD had significantly younger donors than LD, 26.1 ± 13.7 vs. 36.2 ± 9.2 yr (p = 0.006). All the patients received MMF at 600 mg/m2/b.i.d. (maximum dose of 2 g/d) and prednisone with cyclosporine (86%) or tacrolimus (14%). Mean follow-up was >36 months for each group. Acute rejection rate at 6 months was 11.8% (CAD) vs. 15.4% (LD) (p = 0.999) and at 1 yr was 23.5% (CAD) vs. 26.9% (LD) (p = 0.999). Mean estimated glomerular filtration rate (ml/min/1.73 m2) at 6 months was 73.3 ± 15.3 (CAD) vs. 87.6 ± 24.2 (LD) (p = 0.068). Patient survival at 1, 2, and 3 yr was 100, 100, and 100% for CAD vs. 100, 96, and 96% for LD, respectively. Graft survival at 1, 2, and 3 yr was 100, 100, and 94% for CAD vs. 96, 88, and 71% for LD, respectively. Graft loss in CAD was because of chronic rejection (n = 2) while in LD it was because of non-compliance (n = 6), post-transplant lymphoproliferative disorder (n = 1), and sepsis (n = 1). In conclusion, MMF without antibody induction in both CAD and LD pediatric renal transplantation provides statistically similar and effective prophylaxis against acute rejection at 6 months and 1 yr post-transplant. The short-term patient and graft survival rates are excellent, however, non-compliance remains a serious challenge to long-term graft survival. Additional controlled studies are needed to define the role of MMF without antibody induction therapy in pediatric renal transplantation. [source] Once-Daily Prolonged-Release Tacrolimus (ADVAGRAF) Versus Twice-Daily Tacrolimus (PROGRAF) in Liver TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2010P. Trune The efficacy and safety of dual-therapy regimens of twice-daily tacrolimus (BID; Prograf) and once-daily tacrolimus (QD; Advagraf) administered with steroids, without antibody induction, were compared in a multicenter, 1:1-randomized, two-arm, parallel-group study in 475 primary liver transplant recipients. A double-blind, double-dummy 24-week period was followed by an open extension to 12 months posttransplant. The primary endpoint, event rate of biopsy-proven acute rejection (BPAR) at 24 weeks, was 33.7% for tacrolimus BID versus 36.3% for tacrolimus QD (Per-protocol set; p = 0.512; treatment difference 2.6%, 95% confidence interval ,7.3%, 12.4%), falling within the predefined 15% noninferiority margin. At 12 months, BPAR episodes requiring treatment were similar for tacrolimus BID and QD (28.1% and 24.7%). Twelve-month patient and graft survival was 90.8% and 85.6% for tacrolimus BID and 89.2% and 85.3% for tacrolimus QD. Adverse event (AE) profiles were similar for both tacrolimus BID and QD with comparable incidences of AEs and serious AEs. Tacrolimus QD was well tolerated with similar efficacy and safety profiles to tacrolimus BID. [source] Superior Prevention of Acute Rejection by Tacrolimus vs.AMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2006A Large European Trial, Cyclosporine in Heart Transplant Recipients We compared efficacy and safety of tacrolimus (Tac)-based vs. cyclosporine (CyA) microemulsion-based immunosuppression in combination with azathioprine (Aza) and corticosteroids in heart transplant recipients. During antibody induction, patients were randomized (1:1) to oral treatment with Tac or CyA. Episodes of acute rejection were assessed by protocol biopsies, which underwent local and blinded central evaluation. The full analysis set comprised 157 patients per group. Patient/graft survival was 92.9% for Tac and 89.8% for CyA at 18 months. The primary end point, incidence of first biopsy proven acute rejection (BPAR) of grade , 1B at month 6, was 54.0% for Tac vs. 66.4% for CyA (p = 0.029) according to central assessment. Also, incidence of first BPAR of grade , 3A at month 6 was significantly lower for Tac vs. CyA; 28.0% vs. 42.0%, respectively (p = 0.013). Significant differences (p < 0.05) emerged between groups for these clinically relevant adverse events: new-onset diabetes mellitus (20.3% vs. 10.5%); post-transplant arterial hypertension (65.6% vs. 77.7%); and dyslipidemia (28.7% vs. 40.1%) for Tac vs. CyA, respectively. Incidence and pattern of infections over 18 months were comparable between groups, as was renal function. Primary use of Tac during antibody induction resulted in superior prevention of acute rejection without an associated increase in infections. [source] Anti-DNA antibody induction of protein kinase C phosphorylation and fibronectin synthesis in human and murine lupus and the effect of mycophenolic acidARTHRITIS & RHEUMATISM, Issue 7 2009Susan Yung Objective To examine fibronectin (FN) expression in human lupus nephritis and the effect of anti-DNA antibodies on transforming growth factor ,1 (TGF,1) and FN synthesis in cultured human mesangial cells. The effects of mycophenolic acid (MPA) on this pathway, and the effects of mycophenolate mofetil (MMF) treatment in (NZB × NZW)F1/J mice were also studied. Methods Immunohistochemical analyses of renal biopsy samples from patients with active diffuse proliferative lupus nephritis were performed. Cultured human mesangial cells were incubated with human polyclonal anti-DNA antibodies, with or without MPA. (NZB × NZW)F1/J mice with active nephritis were randomized to receive either MMF (100 mg/kg/day) or vehicle treatment for 12 weeks. Results Glomerular FN expression was increased in patients with lupus nephritis, and it colocalized with IgG deposition. Anti-DNA antibodies induced protein kinase C, (PKC,), PKC,I, and PKC,II activation, increased levels of bioactive TGF,1, and increased FN synthesis in human mesangial cells (P < 0.001 for each comparison versus control conditions). Pretreatment of anti-DNA antibodies with exogenous DNA reduced their cellular binding and abrogated their induction of TGF,1 and FN synthesis. Inhibition of PKC activation in human mesangial cells prior to anti-DNA antibody stimulation had no effect on cell proliferation, but resulted in significantly reduced antibody-mediated TGF,1 secretion and FN synthesis. MPA treatment down-regulated PKC,, PKC,I, and PKC,II phosphorylation, reduced levels of TGF,1 bioactivation, and decreased FN synthesis and deposition into the extracellular matrix. MMF treatment in (NZB × NZW)F1/J mice resulted in a reduction in glomerular IgG deposition, PKC activation, and FN expression, as well as an amelioration of proteinuria. Conclusion Human polyclonal anti-DNA antibodies induce TGF,1 and FN synthesis in human mesangial cells through PKC activation, which is inhibited by MPA. [source] Calcineurin inhibitor-sparing regimens in solid organ transplantation: focus on improving renal function and nephrotoxicityCLINICAL TRANSPLANTATION, Issue 1 2008Stuart M Flechner Abstract:, Background:, The calcineurin inhibitors (CNIs), cyclosporine and tacrolimus, have had a revolutionary effect on the overall success of renal transplantation through reduction in early immunologic injury and acute rejection rates. However, the CNIs have a significant adverse impact on renal function and cardiovascular disease, and extended long-term graft survival has not been achieved. The recognition of these effects sparked interest in CNI-sparing strategies. Strategies to limit CNI exposure include CNI minimization, avoidance, and withdrawal. We sought to review the impact of CNI-sparing strategies in kidney, liver, and heart transplantation. Materials and methods:, A PubMed search 1966 to August 2006 was conducted to identify relevant research articles, and the references of these articles as well as the authors' personal files were reviewed. Results:, Calcineurin inhibitor minimization using mycophenolate mofetil or sirolimus may be associated with a modest increase in creatinine clearance (CrCl) and a decrease in serum creatinine (SCr) in the short term. Despite improvement in CrCl or SCr, CNI nephrotoxicity and chronic allograft nephrotoxicity are progressive over time when CNI exposure is maintained. In kidney transplantation, the tubulo-interstitial and glomerular damage are irreversible. Mycophenolate mofetil may improve renal outcomes during CNI minimization more than sirolimus, and antibody induction may be effective to limit CNI exposure, but longer-term follow-up data are required. Use of sirolimus with mycophenolate mofetil or azathioprine to avoid CNI exposure de novo has improved glomerular filtration rate for at least two yr in most studies in kidney transplantation; however, experience is limited in liver and heart transplantation, and reports of delayed graft function and wound healing with sirolimus may have dampened enthusiasm for de novo use. Late CNI withdrawal has achieved variable results, possibly because withdrawal was attempted after the kidney damage was too extensive. Early CNI withdrawal, prior to significant graft damage, has generally improved CrCl and markers of fibrosis and decreased chronic allograft lesions, a finding also observed with sirolimus in most CNI avoidance studies. Successful withdrawal appears to be more effective than CNI minimization. Conclusions:, Calcineurin inhibitors are associated with significant nephrotoxicity and chronic kidney damage. Minimization is associated with a modest increase in renal function, but persistent damage is observed on biopsies as long as the CNIs are continued. Avoidance is hampered by lack of experience and possible sirolimus-induced side effects. CNI withdrawal may be the best option by delivering CNIs during the early period of immunologic graft injury and then converting them to less nephrotoxic agents before significant renal damage occurs. [source] Thymoglobulin induction and steroid avoidance in cardiac transplantation: results of a prospective, randomized, controlled studyCLINICAL TRANSPLANTATION, Issue 1 2008Mohamad H Yamani Abstract:, Background:, Chronic use of corticosteroids (CS) following transplantation is associated with significant long-term morbidities. Minimizing exposure to CS to improve long-term outcomes, without compromising allograft function, remains an important goal in transplantation. Objectives:, This single-center, prospective, randomized, open-label study was designed to evaluate the efficacy of Thymoglobulin® as part of a CS-sparing regimen in cardiac transplantation. Methods:, Thirty-two low-risk cardiac transplant patients were randomized in a 1:1 ratio to receive either a Thymoglobulin-based CS-avoidance regimen (CS-avoidance group; n = 16) or a long-term CS-based regimen with no antibody induction (control group; n = 16). Pulse CS therapy was used for the treatment of acute cellular rejection in both groups. Results:, Baseline characteristics were similar between groups. At one yr, there was no significant difference in the mean incidence of acute cellular rejection (,3A) episodes between the CS-avoidance and control groups, 0.81 ± 1.05 and 1.07 ± 1.03, respectively. Importantly, the CS-avoidance patients had significant improvement in muscle strength and less bone loss compared with the control patients during the first six months post-transplant. Conclusions:, CS-avoidance regimen with Thymoglobulin induction appeared to be safe and effective in cardiac transplantation. Further studies are required to demonstrate the long-term safety and benefits of such a regimen. [source] | ||||||||||