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The safety data collection and evaluation for 172 patients and effectiveness data collection and evaluation for 165 patients were reported. The mean age was 61.9 years. Adverse drug reactions occurred in 18 patients. The mean SDAI decreased from 20.1 at baseline to 11.7 at week 24.
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Patients with T-cell and natural killer-cell lymphomas have poor outcomes. This study examined the role of allogeneic haematopoietic cell transplantation (allo-HCT) after nonmyeloablative conditioning in this setting. Seventeen patients with T-cell lymphoma or NK-cell lymphoma, including three patients in first complete remission, received allo-HCT after 2 Gy total-body irradiation and fludarabine. The median age was 57 (range, 18-73) years. The median number of prior therapies was 3 (range, 1-7), six patients (35%) had failed prior autologous HCT, and five patients (29%) had refractory disease at the time of allograft. Postgrafting immunosuppression was provided with mycophenolate mofetil with ciclosporin or tacrolimus. After a median follow-up of 3.3 (range, 0.3-8.0) years among surviving patients, the estimated probabilities of 3-year overall and progression-free survival were 59% and 53%, respectively, while the estimated probabilities of non-relapse mortality and relapse at 3 years were 19% and 26%, respectively. Sixty-five percent of patients developed grades 2-4 acute graft-versus-host disease and 53% of patients developed chronic graft-versus-host disease. Allo-HCT after nonmyeloablative conditioning is a promising salvage option for selected patients with T-cell and NK-cell lymphomas. These results suggest that graft-versus-T-cell lymphoma activity is responsible for long-term disease control.
This study investigated whether switching from the twice-daily (Prograf; TAC) to the once-daily formulation of tacrolimus with extended release (Advagraf; XL) affected quality of life, anxiety, and transplant benefit perception after allogeneic kidney transplantation.
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Maintenance immunosuppressive pharmacotherapy did not affect isoagglutinin titer levels in ABO-compatible kidney transplants. Further study is needed to investigate the mechanisms of persistent low-level isoagglutinin titers among successful ABOi renal transplantation patients.
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Mixed chimerism established by nonmyeloablative conditioning induces long-term acceptance of CTA, which is associated with persistent chimerism preferentially in the transplanted donor bone.
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One hundred fifty adult de novo heart transplant recipients were enrolled in a prospective, randomized, controlled, open-label trial comparing tacrolimus monotherapy (MONO) with tacrolimus and mycophenolate mofetil therapy (COMBO). Corticosteroids were used in the early postoperative period but discontinued in all patients over 8 to 9 weeks. The primary end point was the composite biopsy score at 6 months after transplant. Patients were followed for 1 to 5 years. The composite biopsy score was similar between groups at 6 and 12 months: 6-month MONO, 0.70 ± 0.44 (95% confidence interval, 0.60 to 0.80) versus COMBO, 0.65 ± 0.40 (95% confidence interval, 0.55 to 0.74; P=0.44). Allograft vasculopathy was assessed by angiography and intravascular ultrasound, with no significant differences noted. Three-year survival was also similar (92.4% MONO versus 97% COMBO; P=0.58, log-rank).
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Tacrolimus is effective in the prevention of acute GVHD. Trials comparing tacrolimus with cyclosporine using tacrolimus levels in the 7 - 10 ng/ml range and with larger numbers of patients may be necessary to better understand the impact of these drugs on survival.
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A cohort of 45 patients following cadaveric renal allograft transplantation were randomly divided into 3 groups based on the regimen of combination of tacrolimus, steroid, and MMF: triple therapy group, steroid withdrawal group, and MMF withdrawal group. During 2 years, survival of patients and allografts, clinical acute rejection, adverse events, hepatic and renal allograft function, and blood lipids were monitored to evaluate the safety and feasibility of steroid or MMF withdrawal after renal transplantation.
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A sustained virological response (SVR) is achieved by 30% of naive liver transplantation (LT) recipients treated with pegylated interferon (PEG-IFN) and ribavirin (RBV). Almost no data are available about retreatment. The aim of this study was to assess the efficacy, tolerability, and SVR predictors of retreatment. Data were collected from 4 centers on the retreatment of prior nonresponders to standard therapy or PEG-IFN (with or without RBV) and relapsers. Seventy-nine of 301 treatment-experienced LT patients (26%), who had a median age of 59 years (range = 35-77 years) and were mostly male (72%) and infected with genotype 1 (87%), were retreated with PEG-IFN and RBV at a median of 6.9 years after LT. During the first course of therapy, 35% were treated with interferon, 49% received tacrolimus, 52% received steroids, and 49.5% were relapsers. Retreatment was started at a median of 1.9 years (range = 45 days to 8.2 years) after the end of the first course. The proportion of patients with cirrhosis increased from 10% to 37% (P < 0.001). In addition, in retreated patients, full initial RBV doses (P = 0.03), growth factors [erythropoietin (P < 0.001) and granulocyte colony-stimulating factor (P = 0.048)], and transfusions (P = 0.03) were used more frequently, and the treatment duration was longer (P = 0.03). An end-of-treatment response was achieved in 61%, whereas SVR, which was associated with improved survival, occurred in 28 (35%). The variables predicting SVR were age (P = 0.04), disease severity [fibrosis (50% with F0-F2 versus 26% with F3-4), P = 0.03; bilirubin, P = 0.006; platelet count, P = 0.03], adherence, and viral kinetics. None of the patients without an early virological response achieved SVR. There was a trend of prior relapsers achieving higher SVR rates than prior nonresponders. In conclusion, SVR, which was achieved by approximately one-third of the retreated patients, can be predicted with the same variables used for naive LT recipients (age, disease severity, adherence, and viral kinetics) and is associated with enhanced survival.
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Disruption of fast axonal transport (FAT) is an early pathological event in Alzheimer's disease (AD). Soluble amyloid-β oligomers (AβOs), increasingly recognized as proximal neurotoxins in AD, impair organelle transport in cultured neurons and transgenic mouse models. AβOs also stimulate hyperphosphorylation of the axonal microtubule-associated protein, tau. However, the role of tau in FAT disruption is controversial. Here we show that AβOs reduce vesicular transport of brain-derived neurotrophic factor (BDNF) in hippocampal neurons from both wild-type and tau-knockout mice, indicating that tau is not required for transport disruption. FAT inhibition is not accompanied by microtubule destabilization or neuronal death. Significantly, inhibition of calcineurin (CaN), a calcium-dependent phosphatase implicated in AD pathogenesis, rescues BDNF transport. Moreover, inhibition of protein phosphatase 1 and glycogen synthase kinase 3β, downstream targets of CaN, prevents BDNF transport defects induced by AβOs. We further show that AβOs induce CaN activation through nonexcitotoxic calcium signaling. Results implicate CaN in FAT regulation and demonstrate that tau is not required for AβO-induced BDNF transport disruption.
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Seven patients received a double kidney transplant from a donor under 3 years old (mean age 2.7 years). The primary renal disease was obstructive uropathy in two patients, and hemolytic uraemic syndrome, tuberous sclerosis, nephronoptisis, reflux nephropathy and nephrotic syndrome (one patient each). Recipients were 14-18 years old and had a mean height of 165.2 cm. Five were in dialysis and it was the second transplantation for two. Both kidneys were sequentially placed in the same iliac fossa; the first was placed the most cranially with the second placed caudal to the first. The surgical technique was similar to that used to place a single graft. Immunosuppression induction employed monoclonal antibodies followed by a triple therapeutic regime (mofetyl micofenolate/steroids/tacrolimus).
First year follow-up after heart transplantation requires invasive tests. Although patients used to be hospitalized for this purpose, ambulatory invasive procedures now offer the possibility of outpatient follow-up. The feasibility and security of this strategy is unknown.
Cabin1 localizes in glomerular podocytes. AngII induces nuclear translocation of Cabin1 in cultured podocytes.
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We reviewed Fontan patients evaluated for HT from 2004 to 2012 with hepatic computed tomography (CT) imaging, classified as normal, non-cirrhotic changes, or cirrhosis. The primary outcome was 1-year all-cause mortality, and the secondary outcome was differences in serial post-HT liver evaluation.
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Almost 50% of total MPA exposure could be explained by the final model, in which proteinuria, glomerular filtration rate, diabetes mellitus, and the mycophenolate mofetil dose were independent determinants of total MPA exposure. Lower glomerular filtration rate (GFR) was independently associated with higher MPA exposure both at 3 and 12 months after transplantation. GFR, alanine aminotransferase, and serum albumin levels and mycophenolate mofetil dose explained 69% of total MPAG exposure variability.
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To build a population pharmacokinetic model that describes the apparent clearance of tacrolimus and the potential demographic, clinical and genetically controlled factors that could lead to inter-patient pharmacokinetic variability within children following liver transplantation.
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Renal allograft biopsies performed after October 2003, representing the first episode of acute rejection (AR) in recipients with > or = 12 months follow-up postbiopsy, were assessed for extent of C4d and correlated with morphology, ELISA screen, donor-specific antibodies (DSA), response to treatment, and outcome.
Prophylactic treatment with ganciclovir decreased the incidence GI CMV infection among seropositive kidney transplant recipients.
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To detect the expression level of macrophage inflammatory protein-1 (MIP-1)α, MIP-1β and monocyte chemoattractant protein-1 (MCP-1) in with psoriasis vulgaris and explore the role in the pathogenesis of psoriasis vulgaris.
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Nutritional autonomy was achieved rapidly, and positive growth was observed in the majority of patients with ITx who received steroid-free immunosuppression with rATG.
We investigated the effects of orally administered olopatadine hydrochloride (olopatadine) on itching, itching mediators, and neuritogenic action in a mouse model.
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These results support the potential of ASP2409 as an improved CTLA4-Ig for maintenance immunosuppression in organ transplantation.
Given the high prevalence of cognitive impairment in the sample, plus the known negative impact of cognitive impairment on clinical outcome, our results indicate that cognitive assessment should be an integrated part of routine clinical follow-up after HTx. However, everolimus- and CNI-based immunosuppressive regimens did not show differential impacts on cognitive function.
Renal transplantation program in the Armed Forces commenced in Feb 1991 and till date 245 patients have undergone renal transplantation at INHS Asvini. We describe our protocols for donor and recipient evaluation and immunosuppression.
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Severity of adult PTSD symptomatology, measured with the modified PTSD Symptom Scale, non-child abuse (primarily adult) trauma exposure and child abuse measured using the traumatic events inventory and 8 SNPs spanning the FKBP5 locus.
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Multitarget therapy may be an attractive option for the treatment of pediatric-onset LN. Further studies involving a larger number of patients are needed.