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Twenty-seven patients with periocular irritant dermatitis (extending onto the face and neck in eight) were treated twice daily with pimecrolimus cream 1% for 7 d, followed by once-daily application for a further 7 d. Erythema, swelling, and pruritus were assessed at baseline, weeks 1-4 using a 4-point clinical score (0, absent; 1, mild; 2, moderate; and 3, severe).
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Hand dermatitis is a chronic inflammatory skin disorder for which systemic immunosuppressive therapy is often needed. Topical treatments could complement the use of systemic corticosteroids.
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The androgen receptor (AR), which mediates the signals of androgens, plays a crucial role in prostate-related diseases. Although widely used, currently marketed anti-androgenic drugs have significant side effects. Several studies have revealed that non-steroidal anti-inflammatory drugs, such as flufenamic acid, block AR transcriptional activity. Herein we describe the development of small molecule analogues of flufenamic acid that antagonize AR. This novel class of AR inhibitors binds to the hormone binding site, blocks AR transcription activity, and acts on AR target genes.
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We describe a renal transplant recipient in whom oliguria developed during the first week after transplant, although his early renal allograft function was good.
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The overall median values of RHI were higher than the value accepted as a normal (1.67). The RHI median value in group 1 was 2.00 (quartile 1: 1.66; quartile 2: 2.72), not different from that in group 2 [1.90 (quartile 1: 1.56; quartile 2: 2.17)] or the controls [2.11 (quartile 1: 1.77; quartile 2: 2.50)]. Multivariate analysis revealed age to be the independent factor influencing RHI in all examined groups but treatment with calcium channel blockers appeared to be the only independent factor influencing RHI among renal transplant recipients. AI% values were not significantly different between the 2 groups of renal transplant recipients, but it was significantly higher among the controls than among subjects treated with tacrolimus.
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The goal of this study was to determine the risk factors for de novo cancer after liver transplantation (LTx). Retrospective analyses were performed in 385 LTx patients who underwent transplantation between 1986 and 2007. In total, 50 (13.0%) recipients developed de novo malignancy. The cumulative incidence of de novo cancer at 1, 5, 10, and 15 years after LTx was 2.9% +/- 0.9%, 10.5% +/- 1.8%, 19.4% +/- 3.0%, and 33.6% +/- 6.8%, respectively. The standardized incidence ratio of malignancy in LTx patients compared to the general population was 2.2 (95% confidence interval: 1.6-2.8). After excluding posttransplant lymphoproliferative disorder and skin cancer, patients with de novo cancer had a significantly lower survival rate compared to recipients who remained cancer-free. The identified univariate risk factors for de novo cancer were cyclosporine A (CsA) treatment, time period of LTx, and recipient age. In multivariate analysis, only CsA treatment emerged as an independent risk factor for de novo cancer, which was attributed to more aggressive cancer types. A surprising finding was that CsA treatment specifically enhanced cancer risk in patients who underwent transplantation after 2004, when C(2) monitoring (blood concentration at 2 hours postdose) was introduced. In addition, these patients showed a significantly lower acute rejection rate, which might reflect a more robust immunosuppressive status caused by the CsA-C(2) regimen. When age was considered, only patients < or =50 years had a higher cancer rate when treated with CsA compared to treatment with tacrolimus. Our data suggest that, compared to tacrolimus treatment, CsA treatment with C(2) monitoring or in younger patients of < or =50 years is associated with a higher early de novo cancer risk after LTx.
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Rho123 uptake in groups treated with CsA and CsA+Rapa was significantly decreased compared to non-treated group and the other immunosupressants in both T cells subsets. Pgp activity was also reduced in CsA and CsA+Rapa compared to the other immunosupressants but it was only significant in the CsA group for CD8+ subset. Kinetic extrusion of Rho123 by Pgp in all groups was faster in CD8+ T cells. All immunosuppressants and the specific Pgp inhibitor PSC833 diminished antigen-primed T-cell proliferation, especially CD8+ T-cell subset.
The use of induction therapy with alphabeta T-cell receptor (alphabetaTCR) monoclonal antibody in association with tacrolimus in an allogeneic rat laryngeal transplant model permits rigorous long-term evaluation of potential short-term synergism offered by these agents.
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Linear morphoea (LM) is a rare fibrosing disorder of the limbs or the face that may cause functional disability and severe aesthetic sequelae. Despite a wide range of therapeutics reported for LM, there is currently a lack of consensus on the optimal therapy. Little is known about the long-term outcome of this disease.
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Patients were treated with T cell-depleting rabbit antithymocyte globulin (rATG) (6 mg/kg, n = 17) or nondepleting, anti-CD25 antibody (basiliximab, 2 × 40 mg, n = 25) induction therapy, in combination with tacrolimus, mycophenolate mofetil, and steroids. Before and the first year after transplantation, IL-7 and IL-2 induced STAT5 phosphorylation, and the expression of the coinhibitory molecules programmed cell death protein 1 (PD-1), T cell immunoglobulin mucin-3 (TIM-3), lymphocyte activation gene-3 (LAG-3), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), cluster of differentiation (CD) 160, and CD244 was measured by flow cytometry.
Influenza vaccination produces a high prevalence of seroprotection in IBD patients, particularly against A strains. The vaccine is well tolerated. Routine influenza vaccination in IBD patients is recommended, irrespective of whether patients receive immunosuppressive medications.
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The main outcome measurements were morphometric analysis performed using a computer program, hematologic or biochemical change, and photography (predominant). It is unclear which was the most effective treatment for vitiligo, however, it was found that these therapies are all promising in the treatment of the disease. With proper care, disease control and repigmentation, even if partial, can be achieved.
One-year graft survival (death-censored) was 93% and 90% (log rank test, P < .01), respectively, for living donor (LD) and DD. Graft losses (15%) were most frequently caused by vascular thrombosis, chronic allograft nephropathy, death with functioning kidney, acute rejection, and recurrent renal disease. Recipients of DD had 2.02 (95% confidence interval: 1.14-3.59) times the hazard of graft loss compared with those of LD (P = .015). Patient survival rates at 1 and 5 years were 98% and 97% for LD and 97% and 93% for DD, respectively. The mortality rate was 3.8%, mainly as the result of infection and cardiovascular disease.
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Although extended release tacrolimus shows promise in improving patient adherence to transplant medication therapy, further studies are needed to confirm improved compliance and to assess long-term safety and efficacy.
The positive rate of urine decoy cell , BKV viruria and viremia in 615 renal recipients were 13.7% (84/615), 29.3% (180/615), and 8.8% (54/615), respectively. BKVAN were diagnosed in 49 recipients. The incidence and the median level of the number of the decoy cell, BK viral load in urine and plasma were higher in the BKVAN group than those in non-BKVAN group (all P<0.05). Tacrolimus (Tac) combined with mycophenolic acid (MPA) protocol (OR=12.4, P=0.001) and severe pneumonia post-transplant (OR=3.7, P=0.001) were the independent risk factors impacting on BKVAN in renal recipients.
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We analysed 61 pregnancies that occurred in 46 patients after having excluded 10 miscarriages during the first trimester and 10 other pregnancies from which important data were missing. Anti-HLA antibodies were screened using the Luminex assay.
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These results suggest that coordinated regulation of these genes influences neurobehavior and demonstrates the importance of examining these alterations in a harmonized fashion.
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We sought to evaluate relationships between the bronchial microbiome and features of severe asthma.
Nine patients received a total of 18 islet infusions. Five patients dropped out in the early phase of the study. Greater than 50% drop-out and noncompliance rate resulted from both poor islet function and recurrent side effects of immunosuppression. The remaining 4 (44%) patients stayed insulin free with intervals for at least over 5 years (cumulative time) after the first transplant. Each of them received 3 infusions, on average 445 000 islet equivalent per transplant. Immunosuppression regimen required multiple adjustments in all patients due to recurrent side effects. In the long-term follow up, kidney function remained stable, and diabetic retinopathy and polyneuropathy did not progress in any of the patients. Patients' panel reactive antibodies remained zero and anti-glutamic acid decarboxylase 65 antibody did not rise after the transplant. Results of metabolic tests including hemoglobin A1c, arginine stimulation, and mixed meal tolerance test were correlated with clinical islet function.
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Immunosuppressive medications often cause posttransplant hyperlipidemia. The effects of cyclosporine (CsA) and tacrolimus (Tac) on lipid profile is well-known; however, there are very few studies related to the effect of these immunosuppressants on fatty acids (FA) of phosholipids fraction (PL) in renal transplant recipients (RTR). We sought to analyze the FA profile in PL fraction of RTR treated with Tac or CsA.
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Atopic dermatitis arises primarily in early infancy. In these patients, corticosteroids are used especially with great caution because of their side effects. Calcineurin inhibitors such as pimecrolimus (PIM) could be useful, but safety concerns have been raised in particular because of the lack of knowledge about their effects on the developing skin immune system. This study was designed to investigate the impact of PIM and corticosteroids on epidermal cells (EC) in infants and newborn mice. We found that the percentage of unfractionated viable infant ECs was significantly decreased in the presence of beta-methasone-17-valerate (BMV) but not PIM. Exposure of unfractionated infant ECs to BMV but not to PIM and vehicle control caused a significant inhibition of the upregulation of CD86 molecules on Langerhans cells (LC). The release of cytokines by LCs and ECs, cultured in the presence of BMV and PIM, was not significantly reduced compared with controls. Topical corticosteroid but not PIM application onto newborn mice induced apoptosis in some LC precursors. Our data suggest that similar to the situation in adult skin, corticosteroids may impair LC maturation as well as viability of ECs in infants, effects not seen with PIM.
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Lesional skin specimens were obtained from eight AD patients and eight normal controls. For 8 weeks, AD patients applied 0.03% tacrolimus ointment to all affected areas twice daily. Blood samples and skin biopsies were then repeated. The participants' serum SP and NGF levels, as well as the SP, NGF, and NT-3 immunoreactive cell counts, were evaluated in the epidermal, dermal, and perivascular areas of lesional skin before and after treatment.
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Antipsoriatic efficacy of methylprednisolone aceponate ointment (MPA), tacrolimus 0.1% ointment (FK506) and their combination (MPA+FK506) were investigated in a double-blind randomized pilot study using the psoriasis plaque test. Agents and corresponding placebos were applied once daily under occlusion for 11 days. Test sites were evaluated by sum score (erythema, scaling, infiltration), objective assessment by 20-MHz-sonography and optical coherence tomography (OCT).
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Objective To measure the expression levels of interleukin-17 (IL-17) and IL-23 mRNAs in the muscle tissue of the mice with experimental autoimmune myositis (EAM), and investigate the impact of tacrolimus (TAC) treatment on the mRNA levels of IL-17 and IL-23 and its therapeutic effect in EAM mice. Methods Fifteen female BALB/c mice were divided randomly into three groups, a normal control group, an EAM model group and a TAC-treated group. HE staining was used to observe the pathological changes for evaluating muscle inflammation of EAM mice. The expression levels of IL-17 and IL-23 mRNAs in the muscle tissues were measured by real-time fluorescence quantitative PCR. Then the correlations between the pathological changes and the expressions of IL-17 and IL-23 mRNAs were analyzed by Pearson methods. Results Compared with the normal controls, the mRNA levels of IL-17 and IL-23 were significantly up-regulated in the EAM model group, and they were down-regulated obviously after TAC treatment. Moreover, the mRNA levels of IL-17 and IL-23 had a significantly positive correlation with the pathological score of the muscle tissues. Compared with the EAM model group, the pathological score of the muscle tissues decreased in the TAC-treated group. Conclusion TAC can down-regulate mRNA levels of IL-17 and IL-23 in the EAM mice.