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Ramin Yaghobi - One of the best experts on this subject based on the ideXlab platform.
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study of the relationships between il 23r il 17 il 21 polymorphisms and serum level of il 17 il 21 with Acute Graft Rejection in iranian liver transplant recipients
Immunological Investigations, 2014Co-Authors: Mohammad Hossein Karimi, Sara Hejr, Bita Geramizadeh, Saman Nikeghbalian, Eskandar Kamalisarvestani, Ramin YaghobiAbstract:Cytokines are important factors determining the outcome of transplantation. Since host ability in cytokine production may be affected by cytokine genes polymorphisms, the aim of the present study was to investigate the effect of IL-17, IL-23R and IL-21 gene polymorphisms in outcome of liver transplantation. A total of 200 liver transplant recipients were included in this study. IL-17 -197 A/G, IL-21 + 1472 G/T, IL-21 5250 C/T, and IL-23R C/A polymorphisms were evaluated by PCR-RFLP or ARMS-PCR methods. The serum levels of IL-17 and IL-21 in rejected and non-rejected groups were determined by ELISA method. The results showed that IL-23R AC carriers and C allele were significantly more frequent in patients with Acute Rejection than patients without Rejection (p = 0.01 and p = 0.0005, respectively). After gender classification, IL-23R AA and AC carriers were significantly more frequent in female patients (p = 0.01, p = 0.01, respectively) and IL-23R AA and AC carriers and A allele were significantly more fre...
Mohammad Hossein Karimi - One of the best experts on this subject based on the ideXlab platform.
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study of the relationships between il 23r il 17 il 21 polymorphisms and serum level of il 17 il 21 with Acute Graft Rejection in iranian liver transplant recipients
Immunological Investigations, 2014Co-Authors: Mohammad Hossein Karimi, Sara Hejr, Bita Geramizadeh, Saman Nikeghbalian, Eskandar Kamalisarvestani, Ramin YaghobiAbstract:Cytokines are important factors determining the outcome of transplantation. Since host ability in cytokine production may be affected by cytokine genes polymorphisms, the aim of the present study was to investigate the effect of IL-17, IL-23R and IL-21 gene polymorphisms in outcome of liver transplantation. A total of 200 liver transplant recipients were included in this study. IL-17 -197 A/G, IL-21 + 1472 G/T, IL-21 5250 C/T, and IL-23R C/A polymorphisms were evaluated by PCR-RFLP or ARMS-PCR methods. The serum levels of IL-17 and IL-21 in rejected and non-rejected groups were determined by ELISA method. The results showed that IL-23R AC carriers and C allele were significantly more frequent in patients with Acute Rejection than patients without Rejection (p = 0.01 and p = 0.0005, respectively). After gender classification, IL-23R AA and AC carriers were significantly more frequent in female patients (p = 0.01, p = 0.01, respectively) and IL-23R AA and AC carriers and A allele were significantly more fre...
Jeanpaul Squifflet - One of the best experts on this subject based on the ideXlab platform.
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correlation of mycophenolic acid pharmacokinetic parameters with side effects in kidney transplant patients treated with mycophenolate mofetil
Clinical Chemistry, 2001Co-Authors: Michel Mourad, Jeanpaul Squifflet, Jacques Malaise, Djamila Chaib Eddour, Martine De Meyer, Josiane Konig, Raf Schepers, Pierre WallemacqAbstract:BACKGROUND: Mycophenolate mofetil (MMF) is widely used in organ transplantation to prevent Acute Rejection. Because MMF can produce hematologic and/or gastrointestinal toxicity, therapeutic monitoring is becoming mandatory. This study was designed to investigate the relationship between the clinical events and the pharmacokinetics of mycophenolic acid (MPA) in adult renal transplantation. METHODS: Thirty-one adult kidney recipients were prospectively included in the study. MPA pharmacokinetic profiles (blood sampling at 0, 0.5, 1, 2, 4, 6, and 12 h after MMF oral dose) were obtained after transplantation (desired creatinine clearance, 40 mL/min), at 3 months after Grafting, and at every clinical event (e.g., side effect or Rejection). All patients received a 10-day course of anti-thymocyte globulin, cyclosporine, MMF (1 g twice daily), and steroids. RESULTS: We divided the 31 patients into two groups (groups 1 and 2). Ten patients (32%; group 1) had uneventful outcomes, and 21 patients (68%; group 2) presented with MPA-related side effects. For groups 1 and 2, the MPA trough concentrations (C(min)) were 1.63 +/- 1.07 and 2.29 +/- 1.16 mg/L, respectively (P = 0.06), and the areas under the curve (AUCs) for MPA from t(0) to t(12 h) (MPA-AUC(0-12h)) were 39.80 +/- 15.29 and 62.10 +/- 21.07 mg. h/L, respectively (P = 0.0005, two-sample t-test). Three patients experienced Acute Graft Rejection after the oral MMF dose was reduced because of side effects. In this group, the MPA-C(min) and MPA-AUC were significantly lower by the time Acute Rejection occurred (1.00 +/- 0.45 mg/L and 25.00 +/- 6.20 mg. h/L, respectively). At a fixed dose (1 g twice per day), we compared the pharmacokinetic parameters of MPA [C(min), the MPA concentration 30 min after the oral dose of MMF (C(30)), and AUC] according to the presence or absence of side effects in the two groups. C:(min) and AUC did not differ between the two groups [C(min) = 2.22 +/- 1.13 vs 2.17 +/- 1.13 mg/L (P = 0.9); AUC = 66.82 +/- 29.87 vs 55.70 +/- 11.74 mg. h/L (P = 0.11)]; and C(30) was significantly higher in group 2 than in group 1 (C(30) = 32.99 +/- 12.59 vs 7.45 +/- 5.40 mg/L; P <0.0001). CONCLUSIONS: Our results demonstrate a pharmacokinetic/pharmacodynamic relationship between MPA and clinical events. At a fixed dose of 2 g/day, a high C(30) is associated with increased risk for side effects. This study suggests that dividing the MMF daily oral dose into more than two divided doses might prevent early MPA toxicity.
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sirolimus in association with mycophenolate mofetil induction for the prevention of Acute Graft Rejection in renal alloGraft recipients
Transplantation, 2000Co-Authors: Henri Kreis, Jeanpaul Squifflet, Jeanmarc Cisterne, W Land, L Wramner, Daniel Abramowicz, Josep Maria Campistol, J M Morales, Josemria Grinyo, Georges MouradAbstract:Introduction. A previous trial in renal transplantation comparing sirolimus (rapamycin) to cyclosporine (CsA) ina triple-drug therapy regimen with azathioprine and corticosteroids found that the incidence of Acute Rejection was similar (approximately 40%) with a trend for better renal function with sirolimus. Methods. In 14 European centers, first cadaveric renal alloGraft recipients were randomized to receive sirolimus (n=40) or CsA (n=38) in an open-label design. All patients received corticosteroids and mycophenolate mofetil 2 g/day. Sirolimus and CsA were concentration controlled; trough levels of mycophenolic acid and prednisolone were also measured. Results. At 12 months, Graft survival(92.5% sirolimus vs. 89.5% CsA), patient survival (97.5% sirolimus vs. 94.7% CsA), and the incidence of biopsy-proven Acute Rejection (27.5% sirolimus vs. 18.4% CsA) were not statistically different. The use of antibodies to treat suspected Rejection episodes was also similar (7.5% sirolimus vs. 5.3% CsA). More sirolimus patients received bolus steroid therapy (20 vs. 11, P=0.068). From month 2 onward, the calculated glomerular filtration rate was consistently higher in sirolimus-treated patients. The adverse events reported more frequently with sirolimus were thrombocytopenia (45% vs. 8%) and diarrhea (38% vs. 11%). In the CsA group, increased creatinine (18% vs. 39%), hyperuricemia (3% vs. 18%), cytomegalovirus infection (5% vs. 21%), and tremor (5% vs. 21%) were observed significantly more often. Discussion. Patient and Graft survival and the incidence of biopsy-proven Acute Rejection at 12 months were comparable between sirolimus and CsA, whereas safety profiles were different. These data suggest that sirolimus may be used as primary therapy for the prevention of Acute Rejection.
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valacyclovir for the prevention of cytomegalovirus disease after renal transplantation
The New England Journal of Medicine, 1999Co-Authors: David Lowance, Christophe Legendre, Douglas J. Norman, Michael R. Keating, Hans H Neumayer, Jeanpaul Squifflet, Josef Kovarik, Patrick J Brennan, Rafael Mendez, Gary L CoggonAbstract:Background Cytomegalovirus (CMV) disease is a major complication of organ transplantation. We hypothesized that prophylactic treatment with valacyclovir would reduce the risk of CMV disease. Methods A total of 208 CMV-negative recipients of a kidney from a seropositive donor and 408 CMV-positive recipients were randomly assigned to receive either 2 g of valacyclovir or placebo orally four times daily for 90 days after transplantation, with the dose adjusted according to renal function. The primary end point was laboratory-confirmed CMV disease in the first six months after transplantation. Results Treatment with valacyclovir reduced the incidence or delayed the onset of CMV disease in both the seronegative patients (P<0.001) and the seropositive patients (P=0.03). Among the seronegative patients, the incidence of CMV disease 90 days after transplantation was 45 percent among placebo recipients and 3 percent among valacyclovir recipients. Among the seropositive patients, the respective values were 6 percent and 0 percent. At six months, the incidence of CMV disease was 45 percent among seronegative recipients of placebo and 16 percent among seronegative recipients of valacyclovir; it was 6 percent among seropositive placebo recipients and 1 percent among seropositive valacyclovir recipients. At six months, the rate of biopsy-confirmed Acute Graft Rejection in the seronegative group was 52 percent among placebo recipients and 26 percent among valacyclovir recipients (P=0.001). Treatment with valacyclovir also decreased the rates of CMV viremia and viruria, herpes simplex virus disease, and the use of inpatient medical resources. Hallucinations and confusion were more common with valacyclovir treatment, but these events were not severe or treatment limiting. The rates of other adverse events were similar among the groups. Conclusions Prophylactic treatment with valacyclovir is a safe and effective way to prevent CMV disease after renal transplantation. (N Engl J Med 1999; 340:1462-70.) (C) 1999, Massachusetts Medical Society.
Reinhard Schwinzer - One of the best experts on this subject based on the ideXlab platform.
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association of high anti donor alloreactivity and low frequency of foxp3 expressing cells prior to kidney transplantation with Acute Graft Rejection
Clinical Transplantation, 2011Co-Authors: Florian W R Vondran, Jürgen Klempnauer, Kai Timrott, Janice Tross, Sonja Kollrich, Frank Lehner, T. Becker, Wilfried Gwinner, Reinhard SchwinzerAbstract:Acute Rejection (AR) is an important factor for the development of chronic alloGraft dysfunction following kidney Tx. Identification of patients who would benefit from closer clinical surveillance to allow indi- vidual tailoring of immunosuppression and hence reducing the rate of AR is highly desired. Aim of this study was to investigate the association of pre- transplant alloreactivity and frequency of regulatory T cells (Tregs) with AR following living-donor kidney Tx. Peripheral blood mononuclear cells were isolated from 40 patients prior to Tx. T-cell alloreactivity against donor and third-party antigen was assessed by proliferative responses in mixed lym- phocyte culture and enzyme linked immunospot technique. Pre-transplant frequency of CD4 + CD25 + CD127 low FoxP3 + Tregs was determined by flow cytometry. Experimental data were correlated with occurrence of AR. We found that patients with Rejection-free (RF) post-Tx courses showed significantly lower pre-transplant alloreactivity to donor antigen compared to individuals with borderline findings (BL) or AR. For RF patients, the proliferative T-cell responses to third-party antigen were significantly higher than for stimulation with donor cells whereas lymphocytes of the AR group showed the inverse pattern. A significantly higher expression of FoxP3 within the CD4 + CD25 + CD127 low subset for RF and BL compared to the
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impact of basiliximab on regulatory t cells early after kidney transplantation down regulation of cd25 by receptor modulation
Transplant International, 2010Co-Authors: Florian W R Vondran, Jürgen Klempnauer, Kai Timrott, Janice Tross, Sonja Kollrich, Frank Lehner, Anke Schwarz, T. Becker, Reinhard SchwinzerAbstract:: Monoclonal anti-CD25-antibodies are successfully applied in organ transplantation to reduce the incidence of Acute Graft Rejection. However, targeting the CD25 molecule might not only affect activated T-cells but also regulatory T-cells (T(regs)) constitutively expressing the CD4(+)CD25(+)CD127(low)FoxP3(+) phenotype. In this study, we investigated the influence of the anti-CD25-antibody Basiliximab on the frequency of T(regs) early after kidney transplantation comparing individuals receiving/not receiving induction therapy (n = 14 and n = 7). Following Basiliximab administration, a distinct loss of CD4(+)CD25(high) T-cells was observed lasting for at least 6 weeks. This was not accompanied by a disappearance of the entire CD4(+)CD25(+)FoxP3(+) T(regs) but rather a decreased expression density of CD25 on the latter. In addition, a transient rise in CD4(+)CD25(-)FoxP3(+) T-cells was found which expressed the CD127(low) phenotype. Thus, a phenotypic shift of T(regs) from the CD25(+) to the CD25(-) compartment was suggested. This was supported by in vitro findings showing that the disappearance of CD4(+)CD25(high) cells in the presence of Basiliximab was due to down-regulation of CD25 expression meanwhile the suppressive function of these cells was maintained. In conclusion, Basiliximab therapy directly affects CD4(+)CD25(+)CD127(low)FoxP3(+) T(regs) but does not seem to be associated with functional consequences. Thus, it is unlikely that Basiliximab treatment negatively influences strategies involving T(regs) to promote tolerance after organ transplantation.
J K Trinkle - One of the best experts on this subject based on the ideXlab platform.
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ventilation perfusion inequalities during Graft Rejection in patients undergoing single lung transplantation for primary pulmonary hypertension
Chest, 1992Co-Authors: Stephanie M Levine, C L Bryan, Antonio Anzueto, Cynthia A Zamora, S G Jenkinson, W J Gibbons, John H Calhoon, J K TrinkleAbstract:We report herein data on single lung transplant (SLT) recipients with primary pulmonary hypertension (PPH). One patient did well following surgery but died on the 30th postoperative day due to cytomegalovirus pneumonia. The remaining two patients initially did well with unlimited exercise tolerance following transplantation, but then developed marked dyspnea on exertion and hypoxemia on postoperative days 144 and 120, respectively. Pulmonary function testing showed marked deterioration of function and transbronchial lung biopsy specimens revealed Acute Graft Rejection in one patient and evidence of chronic Graft Rejection in the second patient. Quantitative ventilation-perfusion lung scanning demonstrated a marked decrease in ventilation to the transplanted lung in both cases associated with only a mild decrease in perfusion. This V/Q mismatch resulted in markedly decreased arterial oxygen saturations, widened alveolar-arterial oxygen gradients, and clinically debilitating dyspnea. We conclude that Rejection may result in significant V/Q mismatch and hypoxemia in PPH patients undergoing SLT, which may limit the use of this specific type of surgery for PPH.