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Sample records for mycophenolate mofetil 500-mg

  1. Validated, Ultra Violet Spectroscopy method for the Dissolution study of Mycophenolate mofetil immediate release 500mg tablets

    OpenAIRE

    Surajpal P. Verma; Ozair Alam; Pooja Mullick; Nadeem Siddiqui; Suroor A. Khan

    2008-01-01

    A simple, selective and precise dissolution method was developed and validated for the Mycophenolate mofetil immediate release tablets. The method employed dissolution medium 0.1N HCl (pH1.2) and volume 900ml with USP-II apparatus (Paddle). Detection was made by measuring the absorbance on UV at the [lambda]~max~ 250nm. The method show the linearity in the range of conc. 5[micro]g/ml to 40[micro]g/ml with r^2^=0.999. The method is also validated as per International Conference of Harmonizatio...

  2. Mycophenolate mofetil attenuates pulmonary arterial hypertension in rats

    International Nuclear Information System (INIS)

    Suzuki, Chihiro; Takahashi, Masafumi; Morimoto, Hajime; Izawa, Atsushi; Ise, Hirohiko; Hongo, Minoru; Hoshikawa, Yasushi; Ito, Takayuki; Miyashita, Hiroshi; Kobayashi, Eiji; Shimada, Kazuyuki; Ikeda, Uichi

    2006-01-01

    Pulmonary arterial hypertension (PAH) is characterized by abnormal proliferation of smooth muscle cells (SMCs), leading to occlusion of pulmonary arterioles, right ventricular (RV) hypertrophy, and death. We investigated whether mycophenolate mofetil (MMF), a potent immunosuppresssant, prevents the development of monocrotaline (MCT)-induced PAH in rats. MMF effectively decreased RV systolic pressure and RV hypertrophy, and reduced the medial thickness of pulmonary arteries. MMF significantly inhibited the number of proliferating cell nuclear antigen (PCNA)-positive cells, infiltration of macrophages, and expression of P-selectin and interleukin-6 on the endothelium of pulmonary arteries. The infiltration of T cells and mast cells was not affected by MMF. In vitro experiments revealed that mycophenolic acid (MPA), an active metabolite of MMF, dose-dependently inhibited proliferation of human pulmonary arterial SMCs. MMF attenuated the development of PAH through its anti-inflammatory and anti-proliferative properties. These findings provide new insight into the potential role of immunosuppressants in the treatment of PAH

  3. [Duodenal villous atrophy associated with Mycophenolate mofetil: report of one case].

    Science.gov (United States)

    Tapia, Oscar; Villaseca, Miguel; Sierralta, Armando; Roa, Juan Carlos

    2010-05-01

    Mycophenolate mofetil (MMF) is an immunosupressor agent frequently used in patients after bone marrow or solid organ transplants. The most common adverse reactions of the drug are gastrointestinal, specially diarrhea and vomiting. We report a 53-year-old male, that received a heart transplant receiving immunosuppression with cyclosporine, mycophenolate mofetil and prednisone. Six months after the transplant, the patient started with diarrhea, anorexia and weight loss. A duodenal biopsy showed villous atrophy. Celiac disease and the presence of parasites were discarded. Mycophenolate mofetil was discontinued and one week later, diarrhea subsided. Two months later the patient was asymptomatic and recovered weight. A new duodenal biopsy showed absence of villous atrophy.

  4. Limited sampling strategies for therapeutic drug monitoring of mycophenolate mofetil therapy in patients with autoimmune disease

    NARCIS (Netherlands)

    de Winter, Brenda C. M.; Neumann, Irmgard; van Hest, Reinier M.; van Gelder, Teun; Mathot, Ron A. A.

    2009-01-01

    Mycophenolate mofetil (MMF) is increasingly used for the treatment of autoimmune diseases (AID). In renal transplant recipients, it has been demonstrated that adjustment of the MMF dose according to the area under the plasma concentration versus time curve (AUC) of mycophenolic acid (MPA), the

  5. Mycophenolate mofetil embryopathy: A newly recognized teratogenic syndrome.

    Science.gov (United States)

    Perez-Aytes, Antonio; Marin-Reina, Purificacion; Boso, Virginia; Ledo, Ana; Carey, John C; Vento, Maximo

    2017-01-01

    Mycophenolate mofetil (MMF) is probably the most common employed immunosuppressant drug in recipients of solid organ transplant and in many autoimmune diseases. In vitro studies, a significant number of single clinical observations and a recent study from a group of different European teratogen information services, have provided very consistent data supporting the existence of a specific MMF embryopathy. The typical malformative pattern of MMF embryopathy includes external ear anomalies ranging from hypoplastic pinna (microtia) to complete absence of pinna (anotia); cleft lip, with or without cleft palate, and ocular anomalies as iris or chorioretinal coloboma and anophthalmia/microphthalmia. Other less frequent features are congenital heart defects, distal limbs anomalies, esophageal atresia, vertebral malformations, diaphragmatic hernia, and kidney and central nervous system anomalies. Neurodevelopmental outcome seems favorable in the small number of patients where information about this issue is available, but neurological deficits have been documented. Physicians in charge of women under MMF therapy should be aware of the potential risk of this drug to cause a specific embryopathy and the need of interrupting the treatment at least six weeks before becoming pregnant. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  6. Mycophenolate mofetil in pediatric renal transplantation: A single center experience.

    LENUS (Irish Health Repository)

    Raheem, Omer A

    2011-05-01

    Raheem OA, Kamel MH, Daly PJ, Mohan P, Little DM, Awan A, Hickey DP. Mycophenolate mofetil in pediatric renal transplantation: A single center experience. Pediatr Transplantation 2011: 15:240-244. © 2009 John Wiley & Sons A\\/S. Abstract:  We assessed our long-term experience with regards to the safety and efficacy of MMF in our pediatric renal transplant population and compared it retrospectively to our previous non-MMF immunosuppressive regimen. Forty-seven pediatric renal transplants received MMF as part of their immunosuppressive protocol in the period from January 1997 till October 2006 (MMF group). A previously reported non-MMF group of 59 pediatric renal transplants was included for comparative analysis (non-MMF group). The MMF group comprised 29 boys and 18 girls, whereas the non-MMF group comprised 34 boys and 25 girls. Mean age was 11.7 and 12 yr in the MMF and non-MMF groups, respectively. The incidence of acute rejection episodes was 11 (23.4%) and 14 (24%) in the MMF and non-MMF group, respectively. Two (3.3%) grafts were lost in the non-MMF group compared with one (2.1%) in the MMF group. Twenty-one (44.68%) patients in the MMF group developed post-transplant infections compared with 12 (20.33%) in the non-MMF group (p < 0.0001). In conclusion, the use of MMF in pediatric renal transplantation was not associated with a lower rejection rate or immunological graft loss. It did, however, result in a significantly higher rate of viral infections.

  7. Mycophenolate mofetil in renal transplantation : 3-year results from the placebo-controlled trial

    NARCIS (Netherlands)

    Behrend, M; Grinyo, J; Vanrenterghem, Y; Rodicio, J; Albrechtsen, D; Sadek, S; Soulillou, JP; van Son, W; Groth, C; Mjornstedt, L; Wiesel, M; Neumayer, HH; Tufveson, G; Ekberg, H; Tarantino, A; Thiel, G; Hene, R; Morgan, A; Ramos, E; Rees, M

    1999-01-01

    Background. The European double-blind, placebo (PLA) controlled study of mycophenolate mofetil (MMF) for prevention of acute renal allograft rejection showed that MMF 2 and 3 g when added to a standard double-drug regimen of cyclosporine and corticosteroids significantly reduced the incidence of

  8. Use of mycophenolate mofetil in patients with severe localized scleroderma resistant or intolerant to methotrexate

    NARCIS (Netherlands)

    Mertens, Jorre S.; Marsman, Diane; van de Kerkhof, Peter C M; Hoppenreijs, Esther P A H; Knaapen, Hanneke K A; Radstake, Timothy R D; de Jong, Elke M G J; Seyger, Marieke M B

    2016-01-01

    To assess the efficacy and safety of mycophenolate mofetil (MMF) in patients with localized scleroderma (LoS) resistant or intolerant to previous treatment with methotrexate (MTX). A case series of patients with LoS treated with MMF. Outcome was assessed through clinical examination. Adverse events

  9. Mycophenolate Mofetil in Combination with Steroids for Treatment of C3 Glomerulopathy: A Case Series.

    Science.gov (United States)

    Avasare, Rupali S; Canetta, Pietro A; Bomback, Andrew S; Marasa, Maddalena; Caliskan, Yasar; Ozluk, Yasemin; Li, Yifu; Gharavi, Ali G; Appel, Gerald B

    2018-03-07

    C3 glomerulopathy is a form of complement-mediated GN. Immunosuppressive therapy may be beneficial in the treatment of C3 glomerulopathy. Mycophenolate mofetil is an attractive treatment option given its role in the treatment of other complement-mediated diseases and the results of the Spanish Group for the Study of Glomerular Diseases C3 Study. Here, we study the outcomes of patients with C3 glomerulopathy treated with steroids and mycophenolate mofetil. We conducted a retrospective chart review of patients in the C3 glomerulopathy registry at Columbia University and identified patients treated with mycophenolate mofetil for at least 3 months and follow-up for at least 1 year. We studied clinical, histologic, and genetic data for the whole group and compared data for those who achieved complete or partial remission (responders) with those who did not achieve remission (nonresponders). We compared remission with mycophenolate mofetil with remission with other immunosuppressive regimens. We identified 30 patients who met inclusion criteria. Median age was 25 years old (interquartile range, 18-36), median creatinine was 1.07 mg/dl (interquartile range, 0.79-1.69), and median proteinuria was 3200 mg/g creatinine (interquartile range, 1720-6759). The median follow-up time was 32 months (interquartile range, 21-68). Twenty (67%) patients were classified as responders. There were no significant differences in baseline characteristics between responders and nonresponders, although initial proteinuria was lower (median 2468 mg/g creatinine) in responders compared with nonresponders (median 5000 mg/g creatinine) and soluble membrane attack complex levels were higher in responders compared with nonresponders. For those tapered off mycophenolate mofetil, relapse rate was 50%. Genome-wide analysis on complement genes was done, and in 12 patients, we found 18 variants predicted to be damaging. None of these variants were previously reported to be pathogenic. Mycophenolate

  10. Mycophenolate mofetil after methotrexate failure or intolerance in the treatment of scleritis and uveitis.

    Science.gov (United States)

    Sobrin, Lucia; Christen, William; Foster, C Stephen

    2008-08-01

    To evaluate the outcomes of treatment with mycophenolate mofetil in patients with scleritis and uveitis refractory to or intolerant of methotrexate. Retrospective noncomparative case series. Eighty-five patients with scleritis and/or uveitis who failed with or did not tolerate methotrexate and were subsequently treated with mycophenolate mofetil between 1998 and 2006. We reviewed medical records of patients who were treated with mycophenolate mofetil after methotrexate intolerance or failure at one tertiary uveitis referral practice. We recorded dose and duration of methotrexate and mycophenolate mofetil therapy, inflammation grade, Snellen visual acuity (VA), use of other immunomodulatory therapy, and adverse events. Multivariate logistic regression was used to identify factors associated with inflammation control. Control of inflammation, steroid-sparing effect, VA, and adverse effects were assessed. Inflammation was controlled with mycophenolate mofetil in 47 patients (55%), with 5 achieving durable remission off all medication. In multivariate logistic regression analysis that adjusted for gender and age, the odds of inflammation control were lower for patients with scleritis (odds ratio [OR], 0.19; 95% confidence interval [CI], 0.04-0.93; P = 0.04) than for patients without scleritis. Among patients without scleritis, the odds of inflammation control were lower for patients with juvenile idiopathic arthritis (JIA)-associated uveitis (OR, 0.14; CI, 0.02-0.81, P = 0.03) compared to patients without JIA-associated uveitis. Eight of the 11 patients (73%) who were taking concomitant prednisone were able to taper their dose to methotrexate. The odds of inflammation control were less in patients with the diagnoses of scleritis and JIA.

  11. A Randomized Clinical Trial Comparing Methotrexate and Mycophenolate Mofetil for Non-Infectious Uveitis

    Science.gov (United States)

    Rathinam, Sivakumar R; Babu, Manohar; Thundikandy, Radhika; Kanakath, Anuradha; Nardone, Natalie; Esterberg, Elizabeth; Lee, Salena M; Enanoria, Wayne TA; Porco, Travis C; Browne, Erica N; Weinrib, Rachel; Acharya, Nisha R

    2014-01-01

    Objective To compare the relative effectiveness of methotrexate and mycophenolate mofetil for non-infectious intermediate uveitis, posterior uveitis, or panuveitis. Design Multicenter, block-randomized, observer-masked clinical trial Participants Eighty patients with non-infectious intermediate, posterior or panuveitis requiring corticosteroid-sparing therapy at Aravind Eye Hospitals in Madurai and Coimbatore, India. Intervention Patients were randomized to receive 25mg weekly oral methotrexate or 1g twice daily oral mycophenolate mofetil and were monitored monthly for 6 months. Oral prednisone and topical corticosteroids were tapered. Main Outcome Measures Masked examiners assessed the primary outcome of treatment success, defined by achieving the following at 5 and 6 months: (1) ≤0.5+ anterior chamber cells, ≤0.5+ vitreous cells, ≤0.5+ vitreous haze and no active retinal/choroidal lesions in both eyes, (2) ≤ 10 mg of prednisone and ≤ 2 drops of prednisolone acetate 1% a day and (3) no declaration of treatment failure due to intolerability or safety. Additional outcomes included time to sustained corticosteroid-sparing control of inflammation, change in best spectacle-corrected visual acuity, resolution of macular edema, adverse events, subgroup analysis by anatomic location, and medication adherence. Results Forty-one patients were randomized to methotrexate and 39 to mycophenolate mofetil. A total of 67 patients (35 methotrexate, 32 mycophenolate mofetil) contributed to the primary outcome. Sixty-nine percent of patients achieved treatment success with methotrexate and 47% with mycophenolate mofetil (p=0.09). Treatment failure due to adverse events or tolerability was not significantly different by treatment arm (p=0.99). There were no statistically significant differences between treatment groups in time to corticosteroid-sparing control of inflammation (p=0.44), change in best spectacle-corrected visual acuity (p=0.68), and resolution of macular

  12. A randomized clinical trial comparing methotrexate and mycophenolate mofetil for noninfectious uveitis.

    Science.gov (United States)

    Rathinam, Sivakumar R; Babu, Manohar; Thundikandy, Radhika; Kanakath, Anuradha; Nardone, Natalie; Esterberg, Elizabeth; Lee, Salena M; Enanoria, Wayne T A; Porco, Travis C; Browne, Erica N; Weinrib, Rachel; Acharya, Nisha R

    2014-10-01

    To compare the relative effectiveness of methotrexate and mycophenolate mofetil for noninfectious intermediate uveitis, posterior uveitis, or panuveitis. Multicenter, block-randomized, observer-masked clinical trial. Eighty patients with noninfectious intermediate, posterior, or panuveitis requiring corticosteroid-sparing therapy at Aravind Eye Hospitals in Madurai and Coimbatore, India. Patients were randomized to receive 25 mg weekly oral methotrexate or 1 g twice daily oral mycophenolate mofetil and were monitored monthly for 6 months. Oral prednisone and topical corticosteroids were tapered. Masked examiners assessed the primary outcome of treatment success, defined by achieving the following at 5 and 6 months: (1) ≤0.5+ anterior chamber cells, ≤0.5+ vitreous cells, ≤0.5+ vitreous haze and no active retinal/choroidal lesions in both eyes, (2) ≤10 mg of prednisone and ≤2 drops of prednisolone acetate 1% a day, and (3) no declaration of treatment failure because of intolerability or safety. Additional outcomes included time to sustained corticosteroid-sparing control of inflammation, change in best spectacle-corrected visual acuity, resolution of macular edema, adverse events, subgroup analysis by anatomic location, and medication adherence. Forty-one patients were randomized to methotrexate and 39 to mycophenolate mofetil. A total of 67 patients (35 methotrexate, 32 mycophenolate mofetil) contributed to the primary outcome. Sixty-nine percent of patients achieved treatment success with methotrexate and 47% with mycophenolate mofetil (P = 0.09). Treatment failure from adverse events or tolerability was not different by treatment arm (P = 0.99). There were no differences between treatment groups in time to corticosteroid-sparing control of inflammation (P = 0.44), change in best spectacle-corrected visual acuity (P = 0.68), or resolution of macular edema (P = 0.31). There was no statistically significant difference in corticosteroid-sparing control of

  13. Effectiveness of cyclosporine and mycophenolate mofetil in a child with refractory evans syndrome

    Directory of Open Access Journals (Sweden)

    Piero Farruggia

    2011-05-01

    Full Text Available Evans Syndrome is a rare autoimmune disease consisting of hemolytic anemia, thrombocytopenia and/or neutropenia. It may be associated with other autoimmune or lymphoproliferative diseases. Its course can be extremely serious and, rarely, even life-threatening; thus it represents a excellent treatment challenge for the pediatric hematologist. First line treatment consists of steroids and/or immunoglobulin; further therapy with rituximab, vincristine, cyclophosphamide and other immunosuppressive drugs can be considered in unresponsive patients. We describe a baby with refractory Evans Syndrome that was cured by prolonged administration of mycophenolate mofetil and remained disease-free for 4 years after the discontinuation of treatment.

  14. PLACEBO-CONTROLLED STUDY OF MYCOPHENOLATE MOFETIL COMBINED WITH CYCLOSPORINE AND CORTICOSTEROIDS FOR PREVENTION OF ACUTE REJECTION

    NARCIS (Netherlands)

    GRINYO, J; GROTH, C; PICHLMAYR, R; SADEK, SA; VANRENTERGHEM, Y; BEHREND, M; LUCK, R; MORESO, F; PEETERS, J; RODICIO, J; MORALES, J; ALBRECHTSEN, D; FAUCHALD, P; SADEK, S; LODGE, J; SOULILLOU, JP; CANTAROVICH, D; van Son, W; Tegzess, Adam; WAGNER, K; ERHARD, J; BRATTSTROM, C; MJORNSTEDT, L; WIESEL, M; CARL, S; NEUMAYER, HH; HAUSER, [No Value; LANG, P; BOURGEON, B; TUFVESON, G; GANNEDAHL, G; EKBERG, H; PERSSON, N; TARANTINO, A; CAMPISE, M; THIEL, G; ZEILER, M; HENE, R; LIGTENBERG, G; MORGAN, A; RIGG, K; HOOFTMAN, L; HUTCHINSON, K

    1995-01-01

    Preliminary studies suggested that mycophenolate mofetil (MMF), which inhibits proliferation of T and B cells, may reduce the frequency of acute rejection after renal transplantation. Our randomised, double-blind, multicentre, placebo-controlled study compared the efficacy and safety of MMF with

  15. Mycophenolate mofetil in erosive genital lichen planus: a case and review of the literature.

    Science.gov (United States)

    Deen, Kristyn; McMeniman, Erin

    2015-03-01

    Erosive genital lichen planus is a disabling, inflammatory mucocutaneous condition that can cause significant patient morbidity and loss of function. Treatment initially involves topical corticosteroids but some patients can have severe treatment-resistant courses requiring systemic immunosuppression. With potentially unfavorable adverse effect profiles and subsequent intolerance of these agents by patients, erosive lichen planus can ultimately be a challenging condition to treat effectively. We present a case of a 66-year-old woman with treatment-resistant erosive genital lichen planus who was successfully managed with mycophenolate mofetil. Although there is only weak evidence for this agent in this condition, its role in dermatology is growing due to its efficacy and advantageous adverse effect profile and should therefore be considered in patients with treatment-resistant erosive genital lichen planus. © 2015 Japanese Dermatological Association.

  16. Inosine monophosphate dehydrogenase messenger RNA expression is correlated to clinical outcomes in mycophenolate mofetil-treated kidney transplant patients, whereas inosine monophosphate dehydrogenase activity is not

    NARCIS (Netherlands)

    Sombogaard, Ferdi; Peeters, Annemiek M. A.; Baan, Carla C.; Mathot, Ron A. A.; Quaedackers, Monique E.; Vulto, Arnold G.; Weimar, Willem; van Gelder, Teun

    2009-01-01

    Measurement of the pharmacodynamic biomarker inosine monophosphate dehydrogenase (IMPDH) activity in renal transplant recipients has been proposed to reflect the biological effect better than using pharmacokinetic parameters to monitor mycophenolate mofetil therapy. The IMPDH assays are however

  17. Mycophenolate Mofetil for the Treatment of Multiple Sclerosis-associated Uveitis.

    Science.gov (United States)

    Hedayatfar, Alireza; Falavarjani, Khalil Ghasemi; Soheilian, Masoud; Elmi Sadr, Navid; Modarres, Mehdi; Parvaresh, Mohammad Mehdi; Naseripour, Masood; Rohani, Mohammad; Almasi, Mostafa; Chee, Soon-Phaik

    2017-06-01

    To report the efficacy of mycophenolate mofetil (MMF) as adjunctive therapy for the treatment of multiple sclerosis (MS)-associated uveitis. In this retrospective, interventional case series, patients with MS-associated uveitis who were treated by MMF as an adjunct therapy to systemic corticosteroid were studied. Patients' demographics, clinical course, response to treatment, and complications were assessed. A total of 30 eyes of 15 patients with a mean age of 34.5 ± 8.3 years were studied. In three patients (20%), onset of uveitis preceded the diagnosis of MS. The course of MS was relapsing-remitting in 11 patients (73.3%) and secondary progressive in four patients (26.7%). At 1 year after institution of MMF, all the patients were on oral prednisolone ≤ 7.5 mg/day, all eyes were quiet without macular edema, and 53.3% of eyes gained visual improvement. Supplemental periocular and intraocular injections were needed during the first 6 months after starting MMF therapy. The systemic adverse effects were transient and minor in severity. MMF had beneficial effects on vision and intraocular inflammation with an acceptable safety profile.

  18. Esophageal Cicatricial Pemphigoid as an Isolated Involvement Treated with Mycophenolate Mofetil

    Directory of Open Access Journals (Sweden)

    Sandra Sánchez Prudencio

    2015-01-01

    Full Text Available Cicatricial pemphigoid (CP is a rare blistering autoimmune disease. Esophageal involvement occurs in widespread disease and rarely appears as the only affected organ. We report a 67-year-old Caucasian female with esophageal dysphagia and weight loss. Several oral panendoscopies showed multiple exudative ulcerations with fibrin and webs in mid- and proximal esophagus and a peeling mucosa. There were no lesions in other organs. We established the diagnosis performing a direct immunofluorescence (DIF, demonstrating IgG3 and complement deposition along the basement membrane. As initial treatment the patient received prednisone 60 mg and 1 gr twice daily of mycophenolate mofetil (MMF as a steroid-sparing agent due to its lower toxicity and its selective mechanism of action. Six months later there was a significant clinical improvement and the esophageal ulcerations had disappeared, developing cicatricial fibrous rings, although no stenosis was present. Four years later, the patient remains asymptomatic with a low maintenance dose of MMF.

  19. Acute pancreatitis induced by mycophenolate mofetil in a kidney transplant patient

    Directory of Open Access Journals (Sweden)

    Einollahi Behzad

    2015-04-01

    Full Text Available Acute pancreatitis is a rare life-threatening complication in patients after kidney transplantation. Here we described a 56-year-old man who had received a living related kidney transplant for an end-stage renal disease. In his regular follow-up, his serum creatinine was gradually increased and he underwent an allograft biopsy, which revealed an interstitial nephritis/tubular atrophy grade II. Mycophenolate mofetil (MMF was prescribed to control chronic allograft nephropathy. He presented with complaints of severe abdominal pain, vomiting, loss of appetite and fever requiring hospital admission twelve days later. Acute pancreatitis was diagnosed on the basis of laboratory data and imaging findings during hospital admission. There was no history of alcohol consumption in our patient. Unfortunately he died one week later and autopsy findings demonstrated acute necrotizing pancreatitis. The bladder drainage of this patients was normal. Laboratory findings in this patient did not endorse infections and other possibilities regarding the etiology of acute pancreatitis in this patient. Therefore, we concluded that acute pancreatitis in near the patient was induced by drugs and basis on our evidence, MMF is the most important suspect. This study suggests that acute pancreatitis can be considered as a side effect of MMF.

  20. Safety of reduced dose of mycophenolate mofetil combined with tacrolimus in living-donor liver transplantation

    Directory of Open Access Journals (Sweden)

    Hyeyoung Kim

    2014-09-01

    Full Text Available Background/AimsThe dose of mycophenolate mofetil (MMF has been reduced in Asia due to side effects associated with the conventional fixed dose of 2-3 g/day. We aimed to determine the pharmacokinetics of a reduced dose of MMF and to validate its feasibility in combination with tacrolimus in living-donor liver transplantation (LDLT.MethodsTwo sequential studies were performed in adult LDLT between October 2009 and 2011. First, we performed a prospective pharmacokinetic study in 15 recipients. We measured the area under the curve from 0 to 12 hours (AUC0-12 for mycophenolic acid at postoperative days 7 and 14, and we performed a protocol biopsy before discharge. Second, among 215 recipients, we reviewed 74 patients who were initially administered a reduced dose of MMF (1.0 g/day with tacrolimus (trough, 8-12 ng/mL during the first month, and 5-8 ng/mL thereafter, with a 1-year follow-up. We performed protocol biopsies at 2 weeks and 1 year post-LDLT.ResultsIn the first part of study, AUC0-12 was less than 30 mgh/L in 93.3% of cases. In the second, validating study, 41.9% of the recipients needed dose reduction or cessation due to side effects within the first year after LDLT. At 12 months post-LDLT, 17.6% of the recipients were administered a lower dose of MMF (0.5 g/day, and 16.2% needed permanent cessation due to side effects. The 1- and 12-month rejection-free survival rates were 98.6% and 97.3%, respectively.ConclusionsA reduced dose of MMF was associated with low blood levels compared to the existing recommended therapeutic range. However, reducing the dose of MMF combined with a low level of tacrolimus was feasible clinically, with an excellent short-term outcome in LDLT.

  1. Impact of dose reductions on efficacy outcome in heart transplant patients receiving enteric-coated mycophenolate sodium or mycophenolate mofetil at 12 months post-transplantation.

    Science.gov (United States)

    Segovia, Javier; Gerosa, Gino; Almenar, Luis; Livi, Ugolino; Viganò, Mario; Arizón, Jose Maria; Yonan, Nizar; Di Salvo, Thomas G; Renlund, Dale G; Kobashigawa, Jon A

    2008-01-01

    Mycophenolic acid (MPA) dose reduction is associated with increased risk of rejection and graft loss in renal transplantation. This analysis investigated the impact of MPA dose changes with enteric-coated mycophenolate sodium (EC-MPS) or mycophenolate mofetil (MMF) in de novo heart transplant recipients. In a 12-month, single-blind trial, 154 patients (EC-MPS, 78; MMF, 76) were randomized to either EC-MPS (1080 mg bid) or MMF (1500 mg bid) in combination with cyclosporine and steroids. The primary efficacy variable was the incidence of treatment failure, comprising a composite of biopsy-proven (BPAR) and treated acute rejection, graft loss or death. Significantly fewer patients receiving EC-MPS required > or =2 dose reductions than patients on MMF (26.9% vs. 42.1% of patients, p = 0.048). Accordingly, the average daily dose of EC-MPS as a percentage of the recommended dose was significantly higher than for MMF (88.4% vs. 79.0%, p = 0.016). Among patients requiring > or =1 dose reduction, the incidence of treated BPAR grade > or =3A was significantly lower with EC-MPS compared with MMF (23.4% vs. 44.0%, p = 0.032). These data suggest that EC-MPS-treated heart transplant patients are less likely to require multiple dose reductions than those on MMF which may be associated with a significantly lower risk of treated BPAR > or =3A.

  2. Pharmacodynamic Monitoring of Inosine Monophosphate Dehydrogenase Activity: A Basis For Optimized and Individualized Mycophenolate Mofetil Therapy

    NARCIS (Netherlands)

    F. Sombogaard (Ferdi)

    2010-01-01

    textabstractIn 1896 Gosic isolated for the first time mycophenolic acid (MPA) from Penicillium glaucum.It was subsequently isolated from Penicillium stoloniferum Thom (synonym P. brevi-compactum Dierckx) by Alsberg and Black in 1913 who gave the acid phenolic substance its name mycophenolic acid

  3. A combined photophysical and computational study on the binding of mycophenolate mofetil and its major metabolite to transport proteins.

    Science.gov (United States)

    Vendrell-Criado, Victoria; González-Bello, Concepción; Miranda, Miguel A; Jiménez, M Consuelo

    2018-06-15

    Binding of the immunosuppressive agent mycophenolate mofetil (MMP) and its pharmacologically active metabolite mycophenolic acid (MPA) to human serum albumin (HSA) and α 1 -acid glycoprotein (HAAG) has been investigated by means of an integrated approach involving selective excitation of the drug fluorophore, following their UV-A triggered fluorescence and docking studies. The formation of the protein/ligand complexes was evidenced by a dramatic enhancement of the fluorescence intensity and a hypsochromic shift of the emission band. In HSA, competitive studies using oleic acid as site I probe revealed site I as the main binding site of the ligands. Binding constants revealed that the affinity of the active metabolite by HSA is four-fold higher than its proactive form. Moreover, the affinity of MMP by HSA is three-fold higher than by HAAG. Docking studies revealed significant molecular binding differences in the binding of MMP and MPA to sub-domain IIA of HSA (site 1). For MPA, the aromatic moiety would be in close contact to Trp214 with the flexible chain pointing to the other end of the sub-domain; on the contrary, for MMP, the carboxylate group of the chain would be fixed nearby Trp214 through electrostatic interactions with residues Arg218 and Arg222. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Do Asian renal transplant patients need another mycophenolate mofetil dose compared with Caucasian or African American patients?

    Science.gov (United States)

    Li, Pengmei; Shuker, Nauras; Hesselink, Dennis A; van Schaik, Ron H N; Zhang, Xianglin; van Gelder, Teun

    2014-10-01

    Mycophenolate mofetil (MMF) is used to prevent acute rejection following solid organ transplantation in transplant centers all over the world. Patients from different ethnic backgrounds are treated with this drug, for which therapeutic drug monitoring (TDM) has not become the standard of practice in most centers. Whether or not some ethnic groups require a different MMF dose has been a topic of debate in recent years. In this review, it is shown that Asian patients, compared with Caucasian patients, with a comparable MMF dose reach higher mycophenolic acid (MPA) exposure. Also clinical experience points toward more adverse events in case of treatment with 1 g MMF bid in Asian patients, and therefore, for this ethnic group, a lower maintenance dose seems justified. In contrast, African American patients reach similar drug concentrations as Caucasians patients receiving the same MMF dose, but due to immunological reasons, they require a higher MMF dose to reach comparable acute rejection incidences. When TDM is performed, clinicians can correct the dose and compensate for interethnic differences in drug exposure. Otherwise, it is important to choose the right dose. This optimal dose is 20-46% lower in Asian transplant recipients than in Caucasian or African American patients. © 2014 Steunstichting ESOT.

  5. Simultaneous determination of mycophenolate mofetil and its active metabolite, mycophenolic acid, by differential pulse voltammetry using multi-walled carbon nanotubes modified glassy carbon electrode

    Energy Technology Data Exchange (ETDEWEB)

    Madrakian, Tayyebeh, E-mail: madrakian@basu.ac.ir; Soleimani, Mohammad; Afkhami, Abbas

    2014-09-01

    A highly sensitive electrochemical sensor for the simultaneous determination of mycophenolate mofetil (MPM) and mycophenolic acid (MPA) was fabricated by multi-walled carbon nanotubes modified glassy carbon electrode (MWCNTs/GCE). The electrochemical behavior of these two drugs was studied at the modified electrode using cyclic voltammetry and adsorptive differential pulse voltammetry. MPM and MPA were oxidized at the GCE during an irreversible process. DPV analysis showed two oxidation peaks at 0.87 V and 1.1 V vs. Ag/AgCl for MPM and an oxidation peak at 0.87 V vs. Ag/AgCl for MPA in phosphate buffer solution of pH 5.0. The MWCNTs/GCE displayed excellent electrochemical activities toward oxidation of MPM and MPA relative to the bare GCE. The experimental design algorithm was used for optimization of DPV parameters. The electrode represents linear responses in the range 5.0 × 10{sup −6} to 1.6 × 10{sup −4} mol L{sup −1} and 2.5 × 10{sup −6} mol L{sup −1} to 6.0 × 10{sup −5} mol L{sup −1} for MPM and MPA, respectively. The detection limit was found to be 9.0 × 10{sup −7} mol L{sup −1} and 4.0 × 10{sup −7} mol L{sup −1} for MPM and MPA, respectively. The modified electrode showed a good sensitivity and stability. It was successfully applied to the simultaneous determination of MPM and MPA in plasma and urine samples. - Highlights: • A new modified electrochemical sensor was constructed and used. • Multiwalled carbon nanotubes were used as the modifiers. • MPM and MPA were measured simultaneously at the low levels. • The sensor was used to the determination of MPA and MPM in real samples.

  6. Managing Drug-Drug Interaction Between Ombitasvir, Paritaprevir/Ritonavir, Dasabuvir, and Mycophenolate Mofetil.

    Science.gov (United States)

    Lemaitre, Florian; Ben Ali, Zeineb; Tron, Camille; Jezequel, Caroline; Boglione-Kerrien, Christelle; Verdier, Marie-Clémence; Guyader, Dominique; Bellissant, Eric

    2017-08-01

    No drug-drug interaction study has been conducted to date for the combination of ombitasvir, paritaprevir/ritonavir, dasabuvir (3D), and mycophenolic acid (MPA). We here report the case of a hepatitis C virus-infected patient treated with 3D and MPA for vasculitis. In light of the threat of drug-drug interaction, the concentration of MPA was measured before, during, and 15 days after the end of the 3D treatment. Similar values were found at all 3 time points, thus indicating that there is probably no need to adapt MPA dosage to 3D.

  7. Mycophenolate mofetil in low-risk renal transplantation in patients receiving no cyclosporine: a single-centre experience.

    LENUS (Irish Health Repository)

    Raheem, Omer A

    2011-05-28

    BACKGROUND: We assess our long-term experience with regards the safety and efficacy of Mycophenolate Mofetil (MMF) in our low risk renal transplant population and compared it retrospectively to Azathioprine (AZA) immunosuppressive regimen. Patients and methods. Between January 1999 and December 2005, 240 renal transplants received MMF as part of their immunosuppressive protocol (MMF group). AZA group of 135 renal transplants was included for comparative analysis (AZA group). Patients received Cyclosporine was excluded from this study. RESULTS: The incidence of biopsy proven 3-month acute rejections was 30 (12.5%) in MMF group and 22 (16%) in AZA group respectively (P = 0.307). Patient survival rates at 1 and 5 years for the MMF group were 97 and 94%, respectively, compared to 100% and 91% at 1 and 5 years respectively for the AZA group (P = 0.61). Graft survival rates at 1 and 5 years for the MMF group were 95 and 83%, respectively, compared to 97 and 84% at 1 and 5 years, respectively for the AZA group (P = 0.62). CONCLUSION: There was no difference in acute rejection episodes between MMF and AZA based immunotherapy. Additionally, we observed no significant difference concerning graft survival in the MMF group when compared to AZA group.

  8. Mycophenolate mofetil in low-risk renal transplantation in patients receiving no cyclosporine: a single-centre experience.

    LENUS (Irish Health Repository)

    2012-02-01

    BACKGROUND: We assess our long-term experience with regards the safety and efficacy of Mycophenolate Mofetil (MMF) in our low risk renal transplant population and compared it retrospectively to Azathioprine (AZA) immunosuppressive regimen. Patients and methods. Between January 1999 and December 2005, 240 renal transplants received MMF as part of their immunosuppressive protocol (MMF group). AZA group of 135 renal transplants was included for comparative analysis (AZA group). Patients received Cyclosporine was excluded from this study. RESULTS: The incidence of biopsy proven 3-month acute rejections was 30 (12.5%) in MMF group and 22 (16%) in AZA group respectively (P = 0.307). Patient survival rates at 1 and 5 years for the MMF group were 97 and 94%, respectively, compared to 100% and 91% at 1 and 5 years respectively for the AZA group (P = 0.61). Graft survival rates at 1 and 5 years for the MMF group were 95 and 83%, respectively, compared to 97 and 84% at 1 and 5 years, respectively for the AZA group (P = 0.62). CONCLUSION: There was no difference in acute rejection episodes between MMF and AZA based immunotherapy. Additionally, we observed no significant difference concerning graft survival in the MMF group when compared to AZA group.

  9. Engineering human T cells for resistance to methotrexate and mycophenolate mofetil as an in vivo cell selection strategy.

    Directory of Open Access Journals (Sweden)

    Mahesh Jonnalagadda

    Full Text Available Gene transfer and drug selection systems that enforce ongoing transgene expression in vitro and in vivo which are compatible with human pharmaceutical drugs are currently underdeveloped. Here, we report on the utility of incorporating human enzyme muteins that confer resistance to the lymphotoxic/immunosuppressive drugs methotrexate (MTX and mycophenolate mofetil (MMF in a multicistronic lentiviral vector for in vivo T lymphocyte selection. We found that co-expression of human dihydrofolate reductase (DHFR(FS; L22F, F31S and inosine monophosphate dehydrogenase II (IMPDH2(IY; T333I, S351Y conferred T cell resistance to the cytocidal and anti-proliferative effects of these drugs at concentrations that can be achieved clinically (up to 0.1 µM MTX and 1.0 µM MPA. Furthermore, using a immunodeficient mouse model that supports the engraftment of central memory derived human T cells, in vivo selection studies demonstrate that huEGFRt(+DHFR(FS+IMPDH2(IY+ T cells could be enriched following adoptive transfer either by systemic administration of MTX alone (4.4 -fold, MMF alone (2.9-fold, or combined MTX and MMF (4.9-fold. These findings demonstrate the utility of both DHFR(FS/MTX and IMPDH2(IY/MMF for in vivo selection of lentivirally transduced human T cells. Vectors incorporating these muteins in combination with other therapeutic transgenes may facilitate the selective engraftment of therapeutically active cells in recipients.

  10. Engineering human T cells for resistance to methotrexate and mycophenolate mofetil as an in vivo cell selection strategy.

    Science.gov (United States)

    Jonnalagadda, Mahesh; Brown, Christine E; Chang, Wen-Chung; Ostberg, Julie R; Forman, Stephen J; Jensen, Michael C

    2013-01-01

    Gene transfer and drug selection systems that enforce ongoing transgene expression in vitro and in vivo which are compatible with human pharmaceutical drugs are currently underdeveloped. Here, we report on the utility of incorporating human enzyme muteins that confer resistance to the lymphotoxic/immunosuppressive drugs methotrexate (MTX) and mycophenolate mofetil (MMF) in a multicistronic lentiviral vector for in vivo T lymphocyte selection. We found that co-expression of human dihydrofolate reductase (DHFR(FS); L22F, F31S) and inosine monophosphate dehydrogenase II (IMPDH2(IY); T333I, S351Y) conferred T cell resistance to the cytocidal and anti-proliferative effects of these drugs at concentrations that can be achieved clinically (up to 0.1 µM MTX and 1.0 µM MPA). Furthermore, using a immunodeficient mouse model that supports the engraftment of central memory derived human T cells, in vivo selection studies demonstrate that huEGFRt(+)DHFR(FS+)IMPDH2(IY+) T cells could be enriched following adoptive transfer either by systemic administration of MTX alone (4.4 -fold), MMF alone (2.9-fold), or combined MTX and MMF (4.9-fold). These findings demonstrate the utility of both DHFR(FS)/MTX and IMPDH2(IY)/MMF for in vivo selection of lentivirally transduced human T cells. Vectors incorporating these muteins in combination with other therapeutic transgenes may facilitate the selective engraftment of therapeutically active cells in recipients.

  11. Prevention of diabetes: effect of mycophenolate mofetil and anti-CD25 on onset of diabetes in the DRBB rat.

    Science.gov (United States)

    Ugrasbul, Figen; Moore, Wayne V; Tong, Pei Ying; Kover, Karen L

    2008-12-01

    Anti-CD25 and mycophenolate mofetil (MMF) treatment of patients with new-onset diabetes is currently being tested as one of the trials in TrialNet. We tested the effectiveness of MMF and anti-CD25 in preventing autoimmune diabetes in the diabetes-resistant biobreeding (DRBB) rat. Autoimmune diabetes in the DRBB rat was induced with a Treg cell depletion regimen starting at 24-26 d of age. Treatment was started on the first day of the depletion regimen in the following groups: (i) control (vehicle); (ii) MMF 25 mg/kg/d intramuscularly daily for 8 wk; (iii) anti-CD25 0.8 mg/kg/d intraperitoneally 5 d/wk for 3 wk; and (iv) combination of MMF and anti-CD25. In a second set of experiments, treatments were started on day 5 of the depletion regimen (delayed treatment) with groups 1, 3, and 4. Rats that had diabetes-free survival for at least 30 d after the treatment was stopped underwent a second Treg depletion (redepletion). In each of the three treatment groups (n = 10/group), onset of diabetes was delayed or prevented in 20, 40 and 80% in groups 2, 3, and 4, respectively. After redepletion, diabetes-free survival was unchanged in group 2 and decreased to 10 and 30% in groups 3 and 4, respectively. With delayed treatment, groups 3 and 4 had 33 and 50% diabetes-free survival that decreased to 0 and 33% after redepletion. MMF and anti-CD25 alone or in combination are effective in delaying and preventing diabetes in the DRBB rat especially if treatment is started before stimulation and expansion of the autoreactive T cells.

  12. The ORION study: comparison of two sirolimus-based regimens versus tacrolimus and mycophenolate mofetil in renal allograft recipients.

    Science.gov (United States)

    Flechner, S M; Glyda, M; Cockfield, S; Grinyó, J; Legendre, Ch; Russ, G; Steinberg, S; Wissing, K M; Tai, S S

    2011-08-01

    Safety and efficacy of two sirolimus (SRL)-based regimens were compared with tacrolimus (TAC) and mycophenolate mofetil (MMF). Renal transplantation recipients were randomized to Group 1 (SRL+TAC; week 13 TAC elimination [n = 152]), Group 2 (SRL + MMF [n = 152]) or Group 3 (TAC + MMF [n = 139]). Group 2, with higher-than-expected biopsy-confirmed acute rejections (BCARs), was sponsor-terminated; therefore, Group 2 two-year data were limited. At 1 and 2 years, respectively, graft (Group 1: 92.8%, 88.5%; Group 2: 90.6%, 89.9%; Group 3: 96.2%, 95.4%) and patient (Group 1: 97.3%, 94.4%; Group 2: 95.2%, 94.5%; Group 3: 97.0%, 97.0%) survival rates were similar. One- and 2-year BCAR incidence was: Group 1, 15.2%, 17.4%; Group 2, 31.3%, 32.8%; Group 3, 8.2%, 12.3% (Group 2 vs. 3, p < 0.001). Mean 1- and 2-year modified intent-to-treat glomerular filtration rates (mL/min) were similar. Primary reason for discontinuation was adverse events (Group 1, 34.2%; Group 2, 33.6%; Group 3, 22.3%; p < 0.05). In Groups 1 and 2, delayed wound healing and hyperlipidemia were more frequent. One-year post hoc analysis of new-onset diabetes posttransplantation was greater in TAC recipients (Groups 1 and 3 vs. 2, 17% vs. 6%; p = 0.004). Between-group malignancy rates were similar. The SRL-based regimens were not associated with improved outcomes for kidney transplantation patients. ©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

  13. FTY720 versus mycophenolate mofetil in de novo renal transplantation: six-month results of a double-blind study.

    Science.gov (United States)

    Tedesco-Silva, Helio; Szakaly, Peter; Shoker, Ahmed; Sommerer, Claudia; Yoshimura, Norio; Schena, Francesco Paolo; Cremer, Malika; Hmissi, Abdel; Mayer, Hartmut; Lang, Philippe

    2007-10-15

    FTY720 is a novel immunomodulator that was developed to produce optimal graft protection with improved safety and tolerability. Phase II studies have demonstrated the efficacy of FTY720 up to the doses of 2.5 mg with full-dose cyclosporine (FDC). This multicenter, double-blind, Phase IIb, randomized study evaluated the safety and efficacy of 5 mg FTY720 (n=87; Group 1) vs. 2.5 mg FTY720 (n=90; Group 2) vs. mycophenolate mofetil (MMF; n=94; Group 3) in de novo renal transplant patients receiving FDC and prednisone. The primary efficacy endpoint was the occurrence of treated biopsy-proven acute rejection, graft loss, death, or premature study discontinuation (composite endpoint) within 6 months. The primary endpoint was superior in Group 1 (24%) and statistically noninferior in Group 2 compared to Group 3 (24.1% vs. 29.2% vs. 39.4%; P=0.025 and 0.0039, respectively). FTY720 plus FDC was generally well tolerated, with a similar incidence of adverse events across all groups. FTY720 was associated with higher incidence of bradycardia (Group 1: 26.4%, P=0.0002 and Group 2: 15.6%, P=0.046, vs. Group 3: 6.4%), respiratory disorders (Group 1: 40.2%, not significant [P=NS] and Group 2: 34.4%, P=NS vs. Group 3: 28.7%). One macular edema occurred in Group 2. Lower creatinine clearances were observed with FTY720 versus MMF (Group 1: 52.4 ml/min, P=NS and Group 2: 51.7 ml/min, P=0.039 vs. Group 3: 62.5 ml/min). Although FTY720 with FDC provided adequate protection from acute rejection the safety profile was less favorable for adverse events than current standard immunosuppression in de novo renal transplant patients.

  14. Mycophenolate mofetil modulates adhesion receptors of the beta1 integrin family on tumor cells: impact on tumor recurrence and malignancy

    International Nuclear Information System (INIS)

    Engl, Tobias; Makarević, Jasmina; Relja, Borna; Natsheh, Iyad; Müller, Iris; Beecken, Wolf-Dietrich; Jonas, Dietger; Blaheta, Roman A

    2005-01-01

    Tumor development remains one of the major obstacles following organ transplantation. Immunosuppressive drugs such as cyclosporine and tacrolimus directly contribute to enhanced malignancy, whereas the influence of the novel compound mycophenolate mofetil (MMF) on tumor cell dissemination has not been explored. We therefore investigated the adhesion capacity of colon, pancreas, prostate and kidney carcinoma cell lines to endothelium, as well as their beta1 integrin expression profile before and after MMF treatment. Tumor cell adhesion to endothelial cell monolayers was evaluated in the presence of 0.1 and 1 μM MMF and compared to unstimulated controls. beta1 integrin analysis included alpha1beta1 (CD49a), alpha2beta1 (CD49b), alpha3beta1 (CD49c), alpha4beta1 (CD49d), alpha5beta1 (CD49e), and alpha6beta1 (CD49f) receptors, and was carried out by reverse transcriptase-polymerase chain reaction, confocal microscopy and flow cytometry. Adhesion of the colon carcinoma cell line HT-29 was strongly reduced in the presence of 0.1 μM MMF. This effect was accompanied by down-regulation of alpha3beta1 and alpha6beta1 surface expression and of alpha3beta1 and alpha6beta1 coding mRNA. Adhesion of the prostate tumor cell line DU-145 was blocked dose-dependently by MMF. In contrast to MMF's effects on HT-29 cells, MMF dose-dependently up-regulated alpha1beta1, alpha2beta1, alpha3beta1, and alpha5beta1 on DU-145 tumor cell membranes. We conclude that MMF possesses distinct anti-tumoral properties, particularly in colon and prostate carcinoma cells. Adhesion blockage of HT-29 cells was due to the loss of alpha3beta1 and alpha6beta1 surface expression, which might contribute to a reduced invasive behaviour of this tumor entity. The enhancement of integrin beta1 subtypes observed in DU-145 cells possibly causes re-differentiation towards a low-invasive phenotype

  15. Mycophenolate mofetil modulates adhesion receptors of the beta1 integrin family on tumor cells: impact on tumor recurrence and malignancy

    Directory of Open Access Journals (Sweden)

    Beecken Wolf-Dietrich

    2005-01-01

    Full Text Available Abstract Background Tumor development remains one of the major obstacles following organ transplantation. Immunosuppressive drugs such as cyclosporine and tacrolimus directly contribute to enhanced malignancy, whereas the influence of the novel compound mycophenolate mofetil (MMF on tumor cell dissemination has not been explored. We therefore investigated the adhesion capacity of colon, pancreas, prostate and kidney carcinoma cell lines to endothelium, as well as their beta1 integrin expression profile before and after MMF treatment. Methods Tumor cell adhesion to endothelial cell monolayers was evaluated in the presence of 0.1 and 1 μM MMF and compared to unstimulated controls. beta1 integrin analysis included alpha1beta1 (CD49a, alpha2beta1 (CD49b, alpha3beta1 (CD49c, alpha4beta1 (CD49d, alpha5beta1 (CD49e, and alpha6beta1 (CD49f receptors, and was carried out by reverse transcriptase-polymerase chain reaction, confocal microscopy and flow cytometry. Results Adhesion of the colon carcinoma cell line HT-29 was strongly reduced in the presence of 0.1 μM MMF. This effect was accompanied by down-regulation of alpha3beta1 and alpha6beta1 surface expression and of alpha3beta1 and alpha6beta1 coding mRNA. Adhesion of the prostate tumor cell line DU-145 was blocked dose-dependently by MMF. In contrast to MMF's effects on HT-29 cells, MMF dose-dependently up-regulated alpha1beta1, alpha2beta1, alpha3beta1, and alpha5beta1 on DU-145 tumor cell membranes. Conclusion We conclude that MMF possesses distinct anti-tumoral properties, particularly in colon and prostate carcinoma cells. Adhesion blockage of HT-29 cells was due to the loss of alpha3beta1 and alpha6beta1 surface expression, which might contribute to a reduced invasive behaviour of this tumor entity. The enhancement of integrin beta1 subtypes observed in DU-145 cells possibly causes re-differentiation towards a low-invasive phenotype.

  16. Dermatose por IgA e IgG linear: relato de caso com boa resposta terapêutica à dapsona e ao micofenolato mofetil Linear IgA/IgG bullous dermatosis: successful treatment with dapsone and mycophenolate mofetil

    Directory of Open Access Journals (Sweden)

    Leny Passos

    2011-08-01

    Full Text Available Relata-se o caso de paciente feminina, de 21 anos, com dermatose por IgA e IgG linear. Inicialmente, a resposta clínica foi favorável à dapsona. Após a interrupção desta medicação, por crise de anemia sintomática, precipitada por malária, houve piora da doença, apesar da utilização da prednisona e pulsoterapia com metilprednisolona. A reintrodução da dapsona, associada ao micofenolato mofetil, possibilitou o controle da enfermidadeA 21-year-old female presenting linear IgA and IgG disease initially responded well to dapsone therapy. However, the treatment with dapsone was withdrawn due to severe anemia induced by malaria, which led to worsening of the clinical picture. Although prednisone and methylprednisolone were tried, the patient responded only to the association of dapsone and mycophenolate mofetil

  17. Age and Early Graft Function Relate With Risk-Benefit Ratio of Allogenic Islet Transplantation Under Antithymocyte Globulin-Mycophenolate Mofetil-Tacrolimus Immune Suppression.

    Science.gov (United States)

    Lee, DaHae; Keymeulen, Bart; Hilbrands, Robert; Ling, Zhidong; Van de Velde, Ursule; Jacobs-Tulleneers-Thevissen, Daniel; Maleux, Geert; Lapauw, Bruno; Crenier, Laurent; De Block, Christophe; Mathieu, Chantal; Pipeleers, Daniel; Gillard, Pieter

    2017-09-01

    Induction therapy with a T cell-depleting agent followed by mycophenolate mofetil and tacrolimus is presently the most frequently used immune suppression (IS) regimen in islet transplantation. This study assesses its safety and tolerability in nonuremic type 1 diabetic recipients. Fifty-one patients (age, between 29 and 63 years) with high glycemic variability and problematic hypoglycemia received intraportal islet grafts under anti-thymocyte globulin-mycophenolate mofetil-tacrolimus protocol. They were followed up for over 48 months for function of the implant and adverse events. Severe hypoglycemia and diabetic ketoacidosis were absent in patients with functioning graft. Immune suppressive therapy was maintained for 48 months in 29 recipients with sustained function (group A), whereas 16 patients stopped earlier due to graft failure (group B) and in 6 for other reasons. Group A was significantly older at the time of implantation and achieved higher graft function at posttransplantation month 6 under similar dose of IS. Prevalence of IS-related side effects was similar in groups A and B, occurring predominantly during the first year posttransplantation. IS-related serious adverse events (SAE) were reported in 47% of patients, with 4 presenting with cytomegalovirus infection and 4 (age, 42-59 years) diagnosed with cancer. Except in 1 patient with cancer, all SAEs resolved after appropriate treatment. These risk/benefit data serve as a basis for clinical decision-making before entering an intraportal islet transplantation protocol. A longer benefit is observed in recipients of higher age (≥40 years), but it is not associated with more side effects and SAE.

  18. Successful treatment of pediatric IgG4 related systemic disease with mycophenolate mofetil: case report and a review of the pediatric autoimmune pancreatitis literature

    Directory of Open Access Journals (Sweden)

    Cron Randy Q

    2011-01-01

    Full Text Available Abstract Autoimmune pancreatitis is frequently associated with elevated serum and tissue IgG4 levels in the adult population, but there are few reports of pediatric autoimmune pancreatitis, and even fewer reports of IgG4 related systemic disease in a pediatric population. The standard of care treatment in adults is systemic corticosteroids with resolution of symptoms in most cases; however, multiple courses of corticosteroids are occasionally required and some patients require long term corticosteroids. In these instances, steroid sparing disease modify treatments are in demand. We describe a 13-year-old girl with IgG4 related systemic disease who presented with chronic recurrent autoimmune pancreatitis resulting in surgical intervention for obstructive hyperbilirubinemia and chronic corticosteroid treatment. In addition, she developed fibrosing medianstinitis as part of her IgG4 related systemic disease. She was eventually successfully treated with mycophenolate mofetil allowing for discontinuation of corticosteroids. This is the first reported use of mycophenolate mofetil for IgG4 related pancreatitis. Although autoimmune pancreatitis as part of IgG4 related systemic disease is rarely reported in pediatrics, autoimmune pancreatitis is also characterized as idiopathic fibrosing pancreatitis. All pediatric autoimmune pancreatitis cases reported in the world medical literature were identified via a PUBMED search and are reviewed herein. Twelve reports of pediatric autoimmune pancreatitis were identified, most of which were treated with corticosteroids or surgical approaches. Most case reports failed to report IgG4 levels, so it remains unclear how commonly IgG4 related autoimmune pancreatitis occurs during childhood. Increased evaluation of IgG4 levels in patients with autoimmune pancreatitis may shed further light on the association of IgG4 with pancreatitis and the underlying pathophysiology.

  19. Efficacy and Safety of Mycophenolate Mofetil and Tacrolimus as Second-line Therapy for Patients With Autoimmune Hepatitis

    DEFF Research Database (Denmark)

    Efe, Cumali; Hagström, Hannes; Ytting, Henriette

    2017-01-01

    BACKGROUND & AIMS: Predniso(lo)ne, alone or in combination with azathioprine, is the standard-of-care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate...

  20. Mycophenolate Mofetil Modulates Differentiation of Th1/Th2 and the Secretion of Cytokines in an Active Crohn's Disease Mouse Model.

    Science.gov (United States)

    Lv, Qing-Kang; Liu, Ju-Xiong; Li, Su-Nan; Gao, Ying-Jie; Lv, Yan; Xu, Zi-Peng; Huang, Bing-Xu; Xu, Shi-Yao; Yang, Dong-Xue; Zeng, Ya-Long; Liu, Dian-Feng; Wang, Wei

    2015-11-06

    Mycophenolate mofetil (MMF) is an alternative immunosuppressive agent that has been reported to be effective and well tolerated for the treatment of refractory inflammatory bowel disease (IBD). The aim of this study was to investigate the therapeutic effect of MMF on intestinal injury and tissue inflammation, which were caused by Crohn's disease (CD). Here, trinitrobenzene sulfonic acid-relapsing (TNBS) colitis was induced in mice; then, we measured the differentiation of Th1/Th2 cells in mouse splenocytes by flow cytometry and the secretion of cytokines in mice with TNBS-induced colitis by real-time polymerase chain reaction and/or enzyme-linked immunosorbent assay (RT-PCR/ELISA). The results show that MMF significantly inhibited mRNA expression of pro-inflammatory cytokines IFN-γ, TNF-α, IL-12, IL-6, and IL-1β in mice with TNBS-induced colitis; however, MMF did not inhibit the expression of IL-10 mRNA. Additionally, ELISA showed that the serum levels of IFN-γ, TNF-α, IL-12, IL-6, and IL-1β were down-regulated in a TNBS model of colitis. Flow cytometric analysis showed MMF markedly reduced the percentages of Th1 and Th2 splenocytes in the CD mouse model. Mycophenolic acid (MPA) also significantly decreased the percentages of splenic Th1 and Th2 cells in vitro. Furthermore, MMF treatment not only significantly ameliorated diarrhea, and loss of body weight but also abrogated the histopathologic severity and inflammatory response of inflammatory colitis, and increased the survival rate of TNBS-induced colitic mice. These results suggest that treatment with MMF may improve experimental colitis and induce inflammatory response remission of CD by down-regulation of pro-inflammatory cytokines via modulation of the differentiation of Th1/Th2 cells.

  1. Diagnostic efficiency of truncated area under the curve from 0 to 2 h (AUC₀₋₂) of mycophenolic acid in kidney transplant recipients receiving mycophenolate mofetil and concomitant tacrolimus.

    Science.gov (United States)

    Lampón, Natalia; Tutor-Crespo, María J; Romero, Rafael; Tutor, José C

    2011-07-01

    Recently, the use of the truncated area under the curve from 0 to 2 h (AUC(0-2)) of mycophenolic acid (MPA) has been proposed for therapeutic monitoring in liver transplant recipients. The aim of our study was the evaluation of the clinical usefulness of truncated AUC(0-2) in kidney transplant patients. Plasma MPA was measured in samples taken before the morning dose of mycophenolate mofetil, and one-half and 2 h post-dose, completing 63 MPA concentration-time profiles from 40 adult kidney transplant recipients. The AUC from 0 to 12 h (AUC(0-12)) was calculated using the validated algorithm of Pawinski et al. The truncated AUC(0-2) was calculated using the linear trapezoidal rule, and extrapolated to 0-12 h (trapezoidal extrapolated AUC(0-12)) as previously described. Algorithm calculated and trapezoidal extrapolated AUC(0-12) values showed high correlation (r=0.995) and acceptable dispersion (ma68=0.71 μg·h/mL), median prediction error (6.6%) and median absolute prediction error (12.6%). The truncated AUC(0-2) had acceptable diagnostic efficiency (87%) in the classification of subtherapeutic, therapeutic or supratherapeutic values with respect to AUC(0-12). However, due to the high inter-individual variation of the drug absorption-rate, the dispersion between both pharmacokinetic variables (ma68=6.9 μg·h/mL) was unacceptable. The substantial dispersion between truncated AUC(0-2) and AUC(0-12) values may be a serious objection for the routine use of MPA AUC(0-2) in clinical practice.

  2. Failure to preserve beta-cell function with mycophenolate mofetil and daclizumab combined therapy in patients with new- onset type 1 diabetes.

    Science.gov (United States)

    Gottlieb, Peter A; Quinlan, Scott; Krause-Steinrauf, Heidi; Greenbaum, Carla J; Wilson, Darrell M; Rodriguez, Henry; Schatz, Desmond A; Moran, Antoinette M; Lachin, John M; Skyler, Jay S

    2010-04-01

    This trial tested whether mycophenolate mofetil (MMF) alone or with daclizumab (DZB) could arrest the loss of insulin-producing beta-cells in subjects with new-onset type 1 diabetes. A multi-center, randomized, placebo-controlled, double-masked trial was initiated by Type 1 Diabetes TrialNet at 13 sites in North America and Europe. Subjects diagnosed with type 1 diabetes and with sufficient C-peptide within 3 months of diagnosis were randomized to either MMF alone, MMF plus DZB, or placebo, and then followed for 2 years. The primary outcome was the geometric mean area under the curve (AUC) C-peptide from the 2-h mixed meal tolerance test. One hundred and twenty-six subjects were randomized and treated during the trial. The geometric mean C-peptide AUC at 2 years was unaffected by MMF alone or MMF plus DZB versus placebo. Adverse events were more frequent in the active therapy groups relative to the control group, but not significantly. Neither MMF alone nor MMF in combination with DZB had an effect on the loss of C-peptide in subjects with new-onset type 1 diabetes. Higher doses or more targeted immunotherapies may be needed to affect the autoimmune process.

  3. Failure to Preserve β-Cell Function With Mycophenolate Mofetil and Daclizumab Combined Therapy in Patients With New- Onset Type 1 Diabetes

    Science.gov (United States)

    Gottlieb, Peter A.; Quinlan, Scott; Krause-Steinrauf, Heidi; Greenbaum, Carla J.; Wilson, Darrell M.; Rodriguez, Henry; Schatz, Desmond A.; Moran, Antoinette M.; Lachin, John M.; Skyler, Jay S.

    2010-01-01

    OBJECTIVE This trial tested whether mycophenolate mofetil (MMF) alone or with daclizumab (DZB) could arrest the loss of insulin-producing β-cells in subjects with new-onset type 1 diabetes. RESEARCH DESIGN AND METHODS A multi-center, randomized, placebo-controlled, double-masked trial was initiated by Type 1 Diabetes TrialNet at 13 sites in North America and Europe. Subjects diagnosed with type 1 diabetes and with sufficient C-peptide within 3 months of diagnosis were randomized to either MMF alone, MMF plus DZB, or placebo, and then followed for 2 years. The primary outcome was the geometric mean area under the curve (AUC) C-peptide from the 2-h mixed meal tolerance test. RESULTS One hundred and twenty-six subjects were randomized and treated during the trial. The geometric mean C-peptide AUC at 2 years was unaffected by MMF alone or MMF plus DZB versus placebo. Adverse events were more frequent in the active therapy groups relative to the control group, but not significantly. CONCLUSIONS Neither MMF alone nor MMF in combination with DZB had an effect on the loss of C-peptide in subjects with new-onset type 1 diabetes. Higher doses or more targeted immunotherapies may be needed to affect the autoimmune process. PMID:20067954

  4. Thymoglobulin induction in liver transplant recipients with a tacrolimus, mycophenolate mofetil, and steroid immunosuppressive regimen: a five-year randomized prospective study.

    Science.gov (United States)

    Boillot, Olivier; Seket, Belhassen; Dumortier, Jérôme; Pittau, Gabriella; Boucaud, Catherine; Bouffard, Yves; Scoazec, Jean-Yves

    2009-11-01

    This randomized, comparative study assessed the long-term efficacy and tolerability of thymoglobulin (TMG) induction in 93 liver transplant patients with an initial regimen of tacrolimus (Tac), mycophenolate mofetil (MMF), and steroids. Forty-four patients were randomly allocated to the TMG+ group, and 49 patients were randomly allocated to the TMG- group. In both groups, Tac was given orally at the initial daily dose of 0.075 mg/kg twice daily, and MMF was given at the initial daily dose of 2 g/day. Steroid withdrawal was planned at 3 months after liver transplantation. The results were evaluated with respect to acute rejection incidence, patient and graft survival, graft function, and medical complications until 5 years or death for all patients. No significant differences were found between groups for the incidence of acute rejection at 5 years (11.4% versus 14.3%), 5-year patient survival (77.3% versus 87.8%), graft function, or postoperative renal function. One patient in the TMG- group underwent retransplantation. There was no difference between groups with respect to the incidence of medical complications, excepted for a higher rate of leukopenia in the TMG+ group, during the 5-year follow-up. In conclusion, the results of this prospective randomized study suggest that the addition of TMG to a triple immunosuppressive regimen (Tac, MMF, and steroids) did not modify the incidence of acute rejection episodes or long-term survival and was responsible for increased leukopenia rates.

  5. Tacrolimus and mycophenolate mofetil after nonmyeloablative matched-sibling donor allogeneic stem-cell transplantations conditioned with fludarabine and low-dose total body irradiation.

    Science.gov (United States)

    Nieto, Yago; Patton, Nigel; Hawkins, Timothy; Spearing, Ruth; Bearman, Scott I; Jones, Roy B; Shpall, Elizabeth J; Rabinovitch, Rachel; Zeng, Chan; Barón, Anna; McSweeney, Peter A

    2006-02-01

    We evaluated tacrolimus/mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis after a nonmyeloablative stem cell transplantation (NST) from a matched sibling donor (MSD). Thirty-two patients (median age, 57 years) with advanced hematologic malignancies, who were poor candidates for a conventional myeloablative transplantation, received fludarabine (30 mg/m(2), day -4 to day -2), total-body irradiation (TBI) (200 cGy, day 0), infusion of donor peripheral blood progenitor cells (day 0), oral tacrolimus 0.06 mg/kg twice daily (from day 3), and oral MMF at 15 mg/kg twice daily (days 0-+27). Tacrolimus was tapered from day +100 to day +180 in those patients with indolent malignancies (n = 25), and from day +35 to day +56 in those with aggressive tumors (n = 7). Regimen toxicities and myelosuppression were mild, allowing 75% of patients to have entirely outpatient transplantations. One patient (3%) experienced a nonfatal graft rejection. Rates of grades II-IV and III-IV acute GVHD were 15.6% and 3%, respectively. Acute GVHD was diagnosed at median day +78 (range, days +31-+84). Extensive chronic GVHD was observed in 10 of 24 evaluable patients (41.6%) at a median onset of day +198 (range, days +128-+277), either spontaneously (n = 5) or elicited after tumor progression (n = 5). Five patients experienced transplantation-related mortality (TRM) (15.6%) from either acute GVHD-related multiorgan failure (MOF) (n = 3) or infectious complications (n = 2). At median follow-up of 19 months (range, 2-41 months), the overall survival, progression-free survival, and disease-free survival rates are 62.5%, 50%, and 40%, respectively. In conclusion, the use of tacrolimus/MMF after MSD NST is associated with encouraging rates of GVHD control.

  6. Conversion from tacrolimus-mycophenolate mofetil to tacrolimus-mTOR immunosuppression after kidney-pancreas transplantation reduces the incidence of both BK and CMV viremia.

    Science.gov (United States)

    Knight, Richard J; Graviss, Edward A; Nguyen, Duc T; Kuten, Samantha A; Patel, Samir J; Gaber, Lillian; Gaber, A Osama

    2018-04-19

    We sought to determine whether conversion from tacrolimus/mycophenolate mofetil (TAC-MMF) into tacrolimus/mTOR inhibitor (TAC-mTOR) immunosuppression would reduce the incidences of BK and CMV viremia after kidney/pancreas (KP) transplantation. In this single-center review, the TAC-mTOR cohort (n = 39) was converted at 1 month post-transplant to an mTOR inhibitor and reduced-dose tacrolimus. Outcomes were compared to a cohort of KP recipients (n = 40) maintained on TAC-MMF. At 3 years post-transplant, KP survivals and incidences of kidney/pancreas rejection were equivalent between mTOR and MMF-treated cohorts. (P = ns). BK viremia-free survival was better for the mTOR vs MMF-treated group (P = .004). In multivariate analysis, MMF vs mTOR immunosuppression was an independent risk factor for BK viremia (hazard ratio 12.27, P = .02). Similarly, mTOR-treated recipients displayed better CMV infection-free survival compared to the MMF-treated cohort (P = .01). MMF vs mTOR immunosuppression (hazard ratio 18.77, P = .001) and older recipient age (hazard ratio 1.13 per year, P = .006) were independent risk factors for CMV viremia. Mean estimated GFR and HgbA1c levels were equivalent between groups at 1, 2, and 3 years post-transplantation. Conversion from TAC/MMF into TAC/mTOR immunosuppression after KP transplantation reduced the incidences of BK and CMV viremia with an equivalent risk of acute rejection and similar renal/pancreas function. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Post-Transplant Cyclophosphamide and Tacrolimus-Mycophenolate Mofetil Combination Prevents Graft-versus-Host Disease in Allogeneic Peripheral Blood Hematopoietic Cell Transplantation from HLA-Matched Donors.

    Science.gov (United States)

    Carnevale-Schianca, Fabrizio; Caravelli, Daniela; Gallo, Susanna; Coha, Valentina; D'Ambrosio, Lorenzo; Vassallo, Elena; Fizzotti, Marco; Nesi, Francesca; Gioeni, Luisa; Berger, Massimo; Polo, Alessandra; Gammaitoni, Loretta; Becco, Paolo; Giraudo, Lidia; Mangioni, Monica; Sangiolo, Dario; Grignani, Giovanni; Rota-Scalabrini, Delia; Sottile, Antonino; Fagioli, Franca; Aglietta, Massimo

    2017-03-01

    Allogeneic hematopoietic cell transplant (HCT) remains the only curative therapy for many hematologic malignancies but it is limited by high nonrelapse mortality (NRM), primarily from unpredictable control of graft-versus-host disease (GVHD). Recently, post-transplant cyclophosphamide demonstrated improved GVHD control in allogeneic bone marrow HCT. Here we explore cyclophosphamide in allogeneic peripheral blood stem cell transplantation (alloPBSCT). Patients with high-risk hematologic malignancies received alloPBSCT from HLA-matched unrelated/related donors. GVHD prophylaxis included combination post-HCT cyclophosphamide 50 mg/kg (days +3 and +4) and tacrolimus/mofetil mycophenolate (T/MMF) (day +5 forward). The primary objective was the cumulative incidence of acute and chronic GVHD. Between March 2011 and May 2015, 35 consecutive patients received the proposed regimen. MMF was stopped in all patients at day +28; the median discontinuation of tacrolimus was day +113. Acute and chronic GVHD cumulative incidences were 17% and 7%, respectively, with no grade IV GVHD events, only 2 patients requiring chronic GVHD immunosuppression control, and no deaths from GVHD. Two-year NRM, overall survival, event-free survival, and chronic GVHD event-free survival rates were 3%, 77%, 54%, and 49%, respectively. The graft-versus-tumor effect was maintained as 5 of 15 patients (33%) who received HCT with evidence of disease experienced further disease response. A post-transplant cyclophosphamide + T/MMF combination strategy effectively prevented acute and chronic GVHD after alloPBSCT from HLA-matched donors and achieved an unprecedented low NRM without losing efficacy in disease control or impaired development of the graft-versus-tumor effect. This trial is registered at clinicaltrials.gov as NCT02300571. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  8. Enteric-coated mycophenolate sodium.

    Science.gov (United States)

    Gabardi, Steven; Tran, Jennifer L; Clarkson, Michael R

    2003-11-01

    To review the pharmacology, pharmacokinetics, efficacy, and safety of mycophenolate sodium. Primary literature was obtained via a MEDLINE search (1966-June 2003). Abstracts were obtained from the manufacturer and included in the analysis. All studies and abstracts evaluating mycophenolate sodium in solid organ transplantation were considered for inclusion. English-language studies and abstracts were selected for inclusion, but were limited to those consisting of human subjects. Mycophenolate sodium, a mycophenolic acid prodrug, is an inhibitor of T-lymphocyte proliferation. Mycophenolic acid reduces the incidence of acute rejection in renal transplantation. Mycophenolate sodium is enteric coated and has been suggested as a potential method to reduce the gastrointestinal adverse events seen with mycophenolate mofetil. Both mycophenolate mofetil and mycophenolate sodium have been shown to be therapeutically equivalent at decreasing the incidence of allograft rejection and loss. The frequency of adverse events is similar between both compounds, with the most common events being diarrhea and leukopenia. Mycophenolate sodium is effective in preventing acute rejection in renal transplant recipients. At doses of 720 mg twice daily, the efficacy and safety profiles are similar to those of mycophenolate mofetil 1000 mg twice daily. Mycophenolate sodium has been approved in Switzerland; approval in the US is pending.

  9. Renal function, efficacy, and safety of sirolimus and mycophenolate mofetil after short-term calcineurin inhibitor-based quadruple therapy in de novo renal transplant patients: one-year analysis of a randomized multicenter trial.

    Science.gov (United States)

    Guba, Markus; Pratschke, Johann; Hugo, Christian; Krämer, Bernhard K; Nohr-Westphal, Constanze; Brockmann, Jens; Andrassy, Joachim; Reinke, Petra; Pressmar, Katharina; Hakenberg, Oliver; Fischereder, Michael; Pascher, Andreas; Illner, Wolf-Dieter; Banas, Bernhard; Jauch, Karl-Walter

    2010-07-27

    De novo sirolimus in calcineurin inhibitor-free regimens, although potentially useful to improve early renal function, are complicated by various drug-related side effects. We report a prospective open-label, multicenter, randomized trial to evaluate early conversion from a CsA-based to a sirolimus (SRL)-based regimen 10 to 24 days after renal transplantation. Of the 196 patients, 141 patients with a low-to-moderate immunological risk were eligible to be converted to SRL or to continue CsA. All patients received antithymocyte globulin-F single-bolus induction, mycophenolate mofetil, and steroids. The primary endpoint, renal function determined by S-creatinine and estimated glomerular filtration rate calculated by Nankivell formula at 12 months was significantly better in the SRL group (1.51+/-0.59 vs. 1.87+/-0.98 mg/dL or 64.5+/-25.2 vs. 53.4+/-18.0 mL/min/1.73 m). Patient survival, graft survival, and incidence of biopsy-proven acute rejection after conversion were not statistically different. Drug discontinuations were significantly higher in the SRL group (36.2% vs. 19.7%). Significantly, more patients in the SRL group reported acne, aphtous, and temporary hyperlipidemia, whereas cytomegalovirus viremia was significantly decreased (7.3% vs. 28.2%). Early conversion to a calcineurin inhibitor-free regimen with SRL in combination with mycophenolate mofetil may be a useful strategy to improve renal function. The identification of appropriate candidates and safe management of SRL-related adverse events will be a key to avoid the high rate of dropouts, which currently limit the broad applicability of this protocol.

  10. Preventing acute rejection, Epstein-Barr virus infection, and posttransplant lymphoproliferative disorders after kidney transplantation: Use of aciclovir and mycophenolate mofetil in a steroid-free immunosuppressive protocol

    DEFF Research Database (Denmark)

    Birkeland, S.A.; Andersen, H.K.; Hamilton-Dutoit, Stephen Jacques

    1999-01-01

    Background: A widely held view is that any increase in the potency of an immunosuppressive agent will lead to an increase in infection and malignancy, such as life-threatening Epstein-Barr virus (EBV) induced posttransplant lymphoproliferative disorders (PTLD), We tested this paradigm by studying......; the effect of adding mofetil to a steroid-free protocol under cover of high-dose aciclovir prophylaxis on the number of acute rejections, EBV infections and PTLDs after kidney transplantation. Methods: EBV serology was performed in 267 consecutive renal transplantations (1990-1997), All were treated...

  11. Mycophenolate mofetil combined with systemic corticosteroids prevents progression to chronic recurrent inflammation and development of 'sunset glow fundus' in initial-onset acute uveitis associated with Vogt-Koyanagi-Harada disease.

    Science.gov (United States)

    Abu El-Asrar, Ahmed M; Dosari, Mona; Hemachandran, Suhail; Gikandi, Priscilla W; Al-Muammar, Abdulrahman

    2017-02-01

    To evaluate the effectiveness and safety of mycophenolate mofetil (MMF) as first-line therapy combined with systemic corticosteroids in initial-onset acute uveitis associated with Vogt-Koyanagi-Harada (VKH) disease. This prospective study included 38 patients (76 eyes). The main outcome measures were final visual acuity, corticosteroid-sparing effect, progression to chronic recurrent granulomatous uveitis and development of complications, particularly 'sunset glow fundus'. The mean follow-up period was 37.0 ± 29.3 (range 9-120 months). Visual acuity of 20/20 was achieved by 93.4% of the eyes. Corticosteroid-sparing effect was achieved in all patients. The mean interval between starting treatment and tapering to 10 mg or less daily was 3.8 ± 1.3 months (range 3-7 months). Twenty-two patients (57.9%) discontinued treatment without relapse of inflammation. The mean time observed off of treatment was 28.1 ± 19.6 months (range 1-60 months). None of the eyes progressed to chronic recurrent granulomatous uveitis. The ocular complications encountered were glaucoma in two eyes (2.6%) and cataract in five eyes (6.6%). None of the eyes developed 'sunset glow fundus', and none of the patients developed any systemic adverse events associated with the treatment. Use of MMF as first-line therapy combined with systemic corticosteroids in patients with initial-onset acute VKH disease prevents progression to chronic recurrent granulomatous inflammation and development of 'sunset glow fundus'. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  12. Micofenolato mofetil na síndrome de Sjögren primária: uma opção para o tratamento da agranulocitose Mycophenolate mofetil in primary Sjögren's syndrome: a treatment option for agranulocytosis

    Directory of Open Access Journals (Sweden)

    Sonia Cristina de Magalhães Souza Fialho

    2012-04-01

    Full Text Available A síndrome de Sjögren (SS é uma doença autoimune caracterizada pela presença de infiltrado linfocítico nas glândulas salivares e lacrimais. Manifestações hematológicas da síndrome de Sjögren primária (SSp geralmente consistem em anemia leve, trombocitopenia, neutropenia moderada e linfopenia. Agranulocitose é raramente descrita e, em geral, responde bem ao tratamento de imunossupressão. Neste trabalho, descrevemos o caso de uma paciente portadora de SSp que apresentou quadro de agranulocitose refratária ao tratamento. A biópsia de medula revelou medula óssea hipocelular com maturação normal da série granulocítica. A paciente foi sucessivamente tratada com prednisona em altas doses, fator estimulador de colônia de macrófagos e ciclosporina, todos sem resposta hematológica. Micofenolato mofetil (MMF foi iniciado, e após dois meses houve aumento na contagem das células brancas. Após um ano de seguimento a paciente não apresentou novos episódios de neutropenia, nem complicações infecciosas. Concluímos que, na agranulocitose refratária associada à SSp, o tratamento com MMF pode ser uma opção eficaz e bem tolerada.The Sjögren's syndrome (SS is an autoimmune disease characterized by a lymphocytic infiltration of salivary and lacrimal glands. Hematological manifestations of primary SS (pSS usually consist of mild anemia, thrombocytopenia, moderate neutropenia, and lymphopenia. Agranulocytosis is rarely reported and usually responds to immunosuppression. We report the case of a pSS patient who presented with refractory agranulocytosis. Bone marrow biopsy disclosed a hypocellular bone marrow with normal maturation of the granulocytic series. The patient was successively treated with high-dose prednisone, granulocyte-macrophage colony stimulation factor, and cyclosporine, with no hematological response. Mycophenolate mofetil (MMF was initiated and after two months there was a rise on the white blood cell count. After

  13. 器官移植患者的霉酚酸酯治疗药物监测%Therapeutic drug monitoring of mycophenolate mofetil in patients undergoing organ transplantation

    Institute of Scientific and Technical Information of China (English)

    崔学艳; 施孝金

    2009-01-01

    麦考酚酸酯(霉酚酸酯,mycophenlate mofetil,MMF)是麦考酚酸(霉酚酸,mycophenolic acid,MPA)的一种酯类衍生物。MMF无生物活性,口服后迅速水解为具活性的MPA。MMF是近年来发现的一种新型免疫抑制剂,临床上主要用于预防和治疗器官移植排斥反应。

  14. Predicting the usefulness of therapeutic drug monitoring of mycophenolic acid: a computer simulation

    NARCIS (Netherlands)

    van Hest, Reinier; Mathot, Ron; Vulto, Arnold; Weimar, Willem; van Gelder, Teun

    2005-01-01

    The usefulness of therapeutic drug monitoring (TDM) of mycophenolate mofetil (MMF) was investigated with a computer simulation model. For a fixed-dose (FD) and a concentration-controlled (CC) MMF dosing regimen exposure to mycophenolic acid (MPA) was compared. A nonlinear mixed-effects model

  15. Mycophenolic Acid Pharmacokinetics and Relapse in Children with Steroid–Dependent Idiopathic Nephrotic Syndrome

    Science.gov (United States)

    Tellier, Stéphanie; Dallocchio, Aymeric; Guigonis, Vincent; Saint-Marcoux, Frank; Llanas, Brigitte; Ichay, Lydia; Bandin, Flavio; Godron, Astrid; Morin, Denis; Brochard, Karine; Gandia, Peggy; Bouchet, Stéphane; Marquet, Pierre; Decramer, Stéphane

    2016-01-01

    Background and objectives Therapeutic drug monitoring of mycophenolic acid can improve clinical outcome in organ transplantation and lupus, but data are scarce in idiopathic nephrotic syndrome. The aim of our study was to investigate whether mycophenolic acid pharmacokinetics are associated with disease control in children receiving mycophenolate mofetil for the treatment of steroid–dependent nephrotic syndrome. Design, setting, participants, & measurements This was a retrospective multicenter study including 95 children with steroid–dependent nephrotic syndrome treated with mycophenolate mofetil with or without steroids. Area under the concentration-time curve of mycophenolic acid was determined in all children on the basis of sampling times at 20, 60, and 180 minutes postdose, using Bayesian estimation. The association between a threshold value of the area under the concentration-time curve of mycophenolic acid and the relapse rate was assessed using a negative binomial model. Results In total, 140 areas under the concentration-time curve of mycophenolic acid were analyzed. The findings indicate individual dose adaptation in 53 patients (38%) to achieve an area under the concentration-time curve target of 30–60 mg·h/L. In a multivariable negative binomial model including sex, age at disease onset, time to start of mycophenolate mofetil, previous immunomodulatory treatment, and concomitant prednisone dose, a level of area under the concentration-time curve of mycophenolic acid >45 mg·h/L was significantly associated with a lower relapse rate (rate ratio, 0.65; 95% confidence interval, 0.46 to 0.89; P=0.01). Conclusions Therapeutic drug monitoring leading to individualized dosing may improve the efficacy of mycophenolate mofetil in steroid–dependent nephrotic syndrome. Additional prospective studies are warranted to determine the optimal target for area under the concentration-time curve of mycophenolic acid in this population. PMID:27445161

  16. Exposure to Mycophenolate and Fatherhood.

    Science.gov (United States)

    Midtvedt, Karsten; Bergan, Stein; Reisæter, Anna Varberg; Vikse, Bjørn Egil; Åsberg, Anders

    2017-07-01

    Mycophenolic acid (MPA) is the active immunosuppressive substance in both mycophenolate mofetil and mycophenolate sodium, and it is widely used after organ transplantation. In women, taking MPA is teratogenic and may also influence spermatogenesis. There is a lack of knowledge regarding outcome of pregnancies fathered by men exposed to MPA. We compared outcomes in pregnancies fathered by renal transplant men per whether they had been exposed to MPA or not at time of conception. A nationwide population-based retrospective cohort study was performed. Data from the Norwegian Renal Registry with all renal transplanted men alive between January 1, 1995 and December 31, 2015 were included, and relevant outcome data were extracted from the Medical Birth Registry of Norway. During the given time, 230 immunosuppressed renal transplanted men fathered 350 children (155 on MPA/195 not on MPA). There were no significant increased risks of malformation (3.9% vs. 2.6%, P = 0.49) in MPA exposed versus unexposed cohorts of children. The average dose (±SD) of mycophenolate was 1.42 ± 0.3 g/day and the individual median MPA trough concentration in the time period of anticipated conception and pregnancy was 2.8 ± 1.6 mg/L. Birth weight was similar in exposed and unexposed cohorts of children; 3381 ± 681 g vs. 3429 ± 714 g (P = 0.53). Paternal exposure to MPA did not increase the risk of adverse birth outcomes in children fathered by male kidney transplanted patients. These results are reassuring and support the continuation of paternal MPA treatment before, during, and after conception.

  17. Mycophenolate mofetil in pediatric renal transplantation: a single center experience.

    LENUS (Irish Health Repository)

    Raheem, Omer A

    2012-02-01

    We assessed our long-term experience with regards to the safety and efficacy of MMF in our pediatric renal transplant population and compared it retrospectively to our previous non-MMF immunosuppressive regimen. Forty-seven pediatric renal transplants received MMF as part of their immunosuppressive protocol in the period from January 1997 till October 2006 (MMF group). A previously reported non-MMF group of 59 pediatric renal transplants was included for comparative analysis (non-MMF group). The MMF group comprised 29 boys and 18 girls, whereas the non-MMF group comprised 34 boys and 25 girls. Mean age was 11.7 and 12 yr in the MMF and non-MMF groups, respectively. The incidence of acute rejection episodes was 11 (23.4%) and 14 (24%) in the MMF and non-MMF group, respectively. Two (3.3%) grafts were lost in the non-MMF group compared with one (2.1%) in the MMF group. Twenty-one (44.68%) patients in the MMF group developed post-transplant infections compared with 12 (20.33%) in the non-MMF group (p < 0.0001). In conclusion, the use of MMF in pediatric renal transplantation was not associated with a lower rejection rate or immunological graft loss. It did, however, result in a significantly higher rate of viral infections.

  18. Evaluation of potential interactions between mycophenolic acid derivatives and proton pump inhibitors.

    Science.gov (United States)

    Gabardi, Steven; Olyaei, Ali

    2012-01-01

    To evaluate the incidence of gastrointestinal (GI) complications in solid organ transplant (SOT) recipients, impact of the complications on transplant outcomes, and the potential interactions between mycophenolic acid (MPA) derivatives and proton pump inhibitors (PPIs). An unrestricted literature search (1980-January 2012) was performed with MEDLINE and EMBASE using the following key words: drug-drug interaction, enteric-coated mycophenolic acid, GI complications, mycophenolate mofetil, solid organ transplant, and proton pump inhibitor, including individual agents within the class. Abstracts from scientific meetings were also evaluated. Additionally, reference citations from identified publications were reviewed. Relevant English-language, original research articles and review articles were evaluated if they focused on any of the topics identified in the search or included substantial content addressing GI complications in SOT recipients or drug interactions. GI complications are frequent among SOT recipients, with some studies showing prevalence rates as high as 70%. Transplant outcomes among renal transplant recipients are significantly impacted by GI complications, especially in patients requiring immunosuppressant dosage reductions or premature discontinuation. To this end, PPI use among patients receiving transplants is common. Recent data demonstrate that PPIs significantly reduce the overall exposure to MPA after oral administration of mycophenolate mofetil. Similar studies show this interaction does not exist between PPIs and enteric-coated mycophenolic acid (EC-MPA). Unfortunately, most of the available data evaluating this interaction are pharmacokinetic analyses that do not investigate the clinical impact of this interaction. A significant interaction exists between PPIs and mycophenolate mofetil secondary to reduced dissolution of mycophenolate mofetil in higher pH environments. EC-MPA is not absorbed in the stomach; therefore, low intragastric acidity

  19. Pharmacokinetic study of mycophenolic acid in Iranian kidney transplant patients

    Directory of Open Access Journals (Sweden)

    Saeed Rezaee

    2013-02-01

    Full Text Available Background: The purpose of this study was to characterize the pharmacokinetic parameters of mycophenolic acid (MPA in Iranian kidney transplant patients. Methods: Plasma MPA concentration of mycophenolate mofetile (MMF 1 gram two times a day was measured in 21 Iranian kidney transplant recipients receiving treatment. Patients who entered the study had been transplanted for more than 3 months and their drug level was supposed to be at steady state. MMF concentration was measured with high-performance liquid chromatography (HPLC. Results: The plasma MPA concentration-time curve was characterized by an early sharp peak at about 1 hour postdose. The mean Area Under Curve (AUC, Cmax and Tmax were 47.0±18.3 µg.h/ml, 18.6±8.5 µg/ml and 1.0±0.5 hours respectively. Conclusion: The plasma MPA concentration-time curve pattern of Iranian patients was similar and consistent with previously reported profiles in other populations taking the same dose. Keywords: Mycophenolate mofetil, Mycophenolic acid, Pharmacokinetics, Area Under Curve, Kidney transplantation

  20. Mycophenolic acid agents: is enteric coating the answer?

    Directory of Open Access Journals (Sweden)

    Manitpisitkul W

    2011-03-01

    Full Text Available Wana Manitpisitkul1, Sabrina Lee2, Matthew Cooper31Department of Pharmacy, University of Maryland Medical Center, Baltimore, MD, USA; 2Solid Organ Transplant Program, University of Utah Health Care, Salt Lake City, UT, USA; 3Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USAAbstract: Addition of mycophenolate mofetil (MMF to calcineurin-based immunosuppressive therapy has led to a significant improvement in graft survival and reduction of acute rejection in renal transplant recipients. However, in clinical practice, MMF dose reduction, interruption, or discontinuation due to hematological and gastrointestinal (GI side-effects occurred in up to 50% of the patients. Large retrospective analyses have demonstrated that patients requiring MMF dose manipulation due to adverse events experienced a higher rate of rejection and graft loss. Enteric-coated mycophenolate sodium (EC-MPS was developed with the goal of improving upper GI side-effects. Here, we review the efficacy and safety of EC-MPS in de novo kidney transplant recipient, and in stable renal transplant patients who were converted from MMF. The changes in GI-related adverse events using patient-reported outcome instruments are also reviewed.Keywords: enteric-coated mycophenolate sodium, mycophenolate mofetil, kidney transplant, efficacy, gastrointestinal tolerability

  1. Efficacy and safety of terbinafine 500 mg once daily in patients with dermatophytosis

    Directory of Open Access Journals (Sweden)

    P Ravindra Babu

    2017-01-01

    Full Text Available Introduction: Dermatophytosis are the most common fungal infections globally. Terbinafine is considered to have good potency against dermatophytes, but resistance to terbinafine is on the rise. Objective: The objective of this study was to evaluate the efficacy and safety of terbinafine 500 mg given once daily in treatment of patients with superficial dermatophytosis. Materials and Methods: It was a retrospective questionnaire-based survey. Each doctor was given survey questionnaire booklet containing survey forms. Clinical response was graded according to the improvement in the affected lesion. Mycological cure was defined as negative microscopy under potassium hydroxide examination and a negative culture in Sabouraud's dextrose agar. Patients were divided into three groups depending on the duration of therapy, Group A – terbinafine 500 mg for 2 weeks, Group B – terbinafine 500 mg for 4 weeks, and Group C – terbinafine 500 mg for 6 weeks. Results: Total 50 doctors completed the survey involving 440 patients. In Group A, out of 194 patients, 87% (n = 169 patients showed very good response. In Group B, out of 211 patients, 92% (n = 194 of the patients showed very good response with >75% improvement in their lesion. In Group C, out of 35 patients, 80% (n = 30 patients showed very good response. Adverse drug reactions of mild to moderate intensity related to terbinafine were seen in 57 patients. Conclusion: Our survey indicates that terbinafine in a dose of 500 mg given once daily was efficacious and safe in the treatment of patients with dermatophytosis.

  2. Efficacy and Safety of Terbinafine 500 mg Once Daily in Patients with Dermatophytosis.

    Science.gov (United States)

    Babu, P Ravindra; Pravin, A J S; Deshmukh, Gaurav; Dhoot, Dhiraj; Samant, Aniket; Kotak, Bhavesh

    2017-01-01

    Dermatophytosis are the most common fungal infections globally. Terbinafine is considered to have good potency against dermatophytes, but resistance to terbinafine is on the rise. The objective of this study was to evaluate the efficacy and safety of terbinafine 500 mg given once daily in treatment of patients with superficial dermatophytosis. It was a retrospective questionnaire-based survey. Each doctor was given survey questionnaire booklet containing survey forms. Clinical response was graded according to the improvement in the affected lesion. Mycological cure was defined as negative microscopy under potassium hydroxide examination and a negative culture in Sabouraud's dextrose agar. Patients were divided into three groups depending on the duration of therapy, Group A - terbinafine 500 mg for 2 weeks, Group B - terbinafine 500 mg for 4 weeks, and Group C - terbinafine 500 mg for 6 weeks. Total 50 doctors completed the survey involving 440 patients. In Group A, out of 194 patients, 87% ( n = 169) patients showed very good response. In Group B, out of 211 patients, 92% ( n = 194) of the patients showed very good response with >75% improvement in their lesion. In Group C, out of 35 patients, 80% ( n = 30) patients showed very good response. Adverse drug reactions of mild to moderate intensity related to terbinafine were seen in 57 patients. Our survey indicates that terbinafine in a dose of 500 mg given once daily was efficacious and safe in the treatment of patients with dermatophytosis.

  3. Brand versus generic dispensing trend for ciprofloxacin 500 mg, levofloxacin 500 mg, and moxifloxacin 400 mg (oral dosage forms) among pharmacies of Karachi, Pakistan.

    Science.gov (United States)

    Zehra, Fatima; Naqvi, Atta Abbas; Tasneem, Sumbul; Ahmad, Rizwan; Ahmad, Niyaz; Shamsi, Adnan Zia; Asghar, Naqiya Ali; Khan, Ghufran Ullah

    2017-01-01

    Pakistan spends 0.7% of its gross domestic product on health. The public sector health-care system provides services to 22% of population thus paving the way for a dominant private sector. Patients in Pakistan mostly pay their medical expenses directly, and 64% of the health expenditures are borne by the household. Expenditure on medicine constitutes 43% of the total household expenditure. A quantitative cross-sectional study was conducted in Karachi, Pakistan, for a month. It was aimed at gathering response from different pharmacies to understand the brand versus generic dispensing trend of ciprofloxacin 500 mg, levofloxacin 500 mg, and moxifloxacin 400 mg oral dosage forms. The study employed convenience sampling and used a survey checklist. The data gathered was entered in SPSS version 22. The mean price per tablet for ciprofloxacin brand and generic was reported at Pakistani Rupees (PKR) 48.44 and PKR 26.85, respectively. The trend for dispensing ciprofloxacin highlighted a split in the market between brand (51%) and generic (49%). For levofloxacin brand and generic, the price per tablet was reported at PKR 36.50 and PKR 36.15 respectively, and despite same price, the market was dominated by generic levofloxacin (92%). Due to a price difference between brand and generic moxifloxacin, i.e., PKR 129.44 and PKR 71.91, respectively, the market was mostly occupied by the generic form (75%). Pricing mechanism must be revisited, and the authorities should take stern actions against any illegitimate price hike. The surging burden of drug expenditure on poorer sections of the society must be addressed by the government on an urgent basis.

  4. Desarrollo de una formulación de tabletas revestidas de secnidazol 500 mg Development of a formulation of coated secnidazole tablets 500 mg

    Directory of Open Access Journals (Sweden)

    Iverlis Díaz Polanco

    2008-04-01

    Full Text Available Se describe el desarrollo de una formulación de tabletas revestidas de secnidazol 500 mg. Durante el desarrollo de esta se evaluaron 2 métodos: la granulación seca y la granulación húmeda. En el revestimiento de las tabletas se empleó un sistema hidroalcohólico con el preparado comercial Policoat YS 1-7003 (Opadry®. Los lotes sometidos a ensayos de estabilidad fueron elaborados a escala piloto, por la vía de granulación húmeda, lo que demostró la factibilidad del proceso de fabricación a esta escala. Las tabletas revestidas presentaron adecuadas propiedades físico-mecánicas y tecnológicas y estas fueron envasadas en frascos de polietileno de alta densidad y en sobres termoconformados de polivinilcloruro/aluminio. La estabilidad química y microbiológica de las tabletas de secnidazol fue estudiada durante 24 meses; los resultados demostraron que estas cumplían con los requisitos establecidos durante este periodoThe development of a formulation of coated Secnidazole tablets 500mg was described. During its development, 2 methods were evaluated: dry granulation and humid granulation. A hydroalcoholic system was used with the Policoat YS 1-7003 (Opadry® commercial preparation for coating the tablets. The batches subjected to stability assays were made at pilot scale by humid granulation, which showed the feasibility of the manufacturing process at this scale. The coated tablets had adequate physicomechanical and technological properties and they were packed in polyethylene flasks of high density and in polyvinyl chloride/aluminium thermoconformed envelopes. The chemical and microbiological stability of the secnidazole tablets were studied during 24 months. The results demonstrated that these tablets met the requirements established during this period

  5. Mycophenolic acid AUC in Thai kidney transplant recipients receiving low dose mycophenolate and its association with UGT2B7 polymorphisms.

    Science.gov (United States)

    Pithukpakorn, Manop; Tiwawanwong, Tiwat; Lalerd, Yupaporn; Assawamakin, Anunchai; Premasathian, Nalinee; Tasanarong, Adis; Thongnoppakhun, Wanna; Vongwiwatana, Attapong

    2014-01-01

    Despite use of a lower mycophenolate dose in Thai kidney transplant patients, acceptable graft and patient outcomes can be achieved. We therefore examined the pharmacokinetics of mycophenolic acid (MPA) by area under the curve (AUC) and investigated genetic contribution in mycophenolate metabolism in this population. Kidney transplant recipients with stable graft function who were receiving mycophenolate mofetil 1,000 mg/d in combination with either cyclosporine or tacrolimus, and prednisolone were studied. The MPA concentration was measured by fluorescence polarization immunoassay (FPIA), at predose and 1, 1.5, 2, 4, 6, 8, 10, and 12 hours after dosing. Genetic polymorphisms in UGT1A8, UGT1A9, and UGT2B7 were examined by denaturing high-performance liquid chromatography (DHPLC)-based single-base extension (SBE) analysis. A total 138 patients were included in study. The mean AUC was 39.49 mg-h/L (28.39-89.58 mg-h/L), which was in the therapeutic range. The correlation between the predose MPA concentration and AUC was poor. The mean AUC in the tacrolimus group was higher than that in the cyclosporine group. Polymorphisms in UGT2B7 showed significant association with AUC. Most of our patients with reduced mycophenolate dose had the AUC within the therapeutic range. Genetic polymorphisms in UGT2B7 may play a role in MPA metabolism in Thai kidney transplant patients.

  6. Effect of binders on 500mg metformin hydrochloride tablets produced by wet granulation

    Directory of Open Access Journals (Sweden)

    LUCIANA CATIA BLOCK

    2009-12-01

    Full Text Available Metformin hydrochloride (MH is an oral hypoglycemic agent and a high-dose drug that has poor flow and compression properties. In this study, the feasibility of developing adequate, low cost 500mg tablets of metformin hydrochloride by wet granulation was tested with several binders (Starch / PVP K30®; Starch 1500® /PVP K30®, PVP K30® and PVP K90® in a simple tablet press of the type used in small pharmaceutical laboratories. The drug powder was tested for ability to flow, by determining Carr’s Index (CI and the Hausner ratio (HR. Differential scanning calorimetry and thermogravimetric analysis were carried out on isolated MH and 1:1 (w/w binary mixtures with the excipients. The size distribution, friability, flow properties and drug content of the granules were analyzed, as were the hardness, friability, disintegration, dissolution and uniformity of the dosage form. The drug powder showed CI > 22% and HR > 1.25, characteristic of a poor flow powder, and no significant incompatibilities with the excipients. All the granules showed adequate flow properties and were suitable for pressing into tablets, all of which complied with pharmacopeial specifications. The starch /PVP K30® and starch 1500® /PVP K30® mixtures were best for producing 500 mg MH tablets. Keywords: Metformin hydrochloride. Tablets. Wet granulation. Binders.

  7. Métodos analíticos necesarios para el desarrollo de tabletas de metformina 500 mg Analytical methods needed for Metformin 500mg tablets development

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    Caridad M. García Peña

    2009-12-01

    Full Text Available El clorhidrato de metformina es un derivado de la biguanida usado en la diabetes mellitus no insulina dependiente, reduce la concentración de glucosa sanguínea sin incrementar la secreción de insulina, se considera un agente antihiperglucemiante y no un fármaco hipoglucemiante. El desarrollo tecnológico requiere de métodos analíticos confiables que permitan la cuantificación del fármaco en diferentes etapas de la investigación. El objetivo de este trabajo fue la validación del método analítico, reportado en la Farmacopea de los Estados Unidos (USP 31, 2008, por espectrofotometría ultravioleta y la adaptación del método analítico, reportado en la misma farmacopea, para el análisis de los compuestos relacionados en la determinación del principio activo en el producto terminado, por cromatografía líquida de alta resolución, validados para el control de la calidad y estudio de estabilidad de las tabletas de metformina 500 mg. A las técnicas validadas, por métodos cromatográficos y espectrofotométricos se le determinaron los parámetros de desempeño, especificidad, linealidad, exactitud y precisión. Las curvas de calibración para cada método, se realizaron en el intervalo de 60 al 140 %, donde fueron lineales con coeficientes de correlación igual a 0,9994 y 0,99903, respectivamente; la prueba estadística para el intercepto y la pendiente se consideró no significativa. Se obtuvieron recobrados de 100,01 y 99,1 %, respectivamente, en el intervalo de concentraciones estudiados y las pruebas de Cochran´(G y Student´s (t resultaron no significativas. Los coeficientes de variación en los estudios de la repetibilidad fueron iguales a 1,4 y 0,8 %, respectivamente, para las 6 réplicas ensayadas, mientras que en los análisis de la precisión intermedia las pruebas de Fischer y Student fueron no significativas. Los resultados permiten concluir que ambos métodos cumplen con los requisitos establecidos como aceptables para

  8. Clinical efficacy of levofloxacin 500 mg once daily for 7 days for patients with non-gonococcal urethritis.

    Science.gov (United States)

    Takahashi, Satoshi; Ichihara, Kohji; Hashimoto, Jiro; Kurimura, Yuichiro; Iwasawa, Akihiko; Hayashi, Kenji; Sunaoshi, Kenichi; Takeda, Koichi; Suzuki, Nobukazu; Satoh, Takashi; Tsukamoto, Taiji

    2011-06-01

    To confirm the efficacy of the treatment regimen with oral levofloxacin (LVFX) 500 mg once daily for 7 days for patients with non-gonococcal urethritis (NGU), we evaluated the microbiological and clinical outcomes of the regimen in those patients. We finally evaluated 53 patients with symptomatic NGU and 5 patients with asymptomatic NGU. As a result of microbiological examinations, 19 of the symptomatic patients were diagnosed as having non-gonococcal chlamydial urethritis (NGCU); 13 had non-gonococcal non-chlamydial urethritis (NGNCU), and 21 had urethritis without any microbial detection. Five of the asymptomatic patients were diagnosed as having NGCU. Microbiological cure was achieved in 91% of the 32 patients with symptomatic NGU and in 80% of the 5 patients with asymptomatic NGCU. Clinical cure was obtained in 92% of the 53 patients with symptomatic NGU. The microbiological eradication rate for Chlamydia trachomatis was 92% in 24 patients. As for other organisms, the microbiological eradication rate for Mycoplasma genitalium was 60% in 5 patients and that for Ureaplasma urealyticum was 100% in 10. The microbiological and clinical efficacy of oral LVFX 500 mg once daily for 7 days for the patients with NGU was the same for the azithromycin (AZM) 1,000 mg single dose that we previously reported. The eradication rates of C. trachomatis and U. urealyticum in the treatment regimen with LVFX 500 mg were high enough in the clinical setting; however, for M. genitalium, the rate was relatively inferior to that with AZM.

  9. Enteric-coated mycophenolate sodium experience in liver transplant patients.

    Science.gov (United States)

    Cantisani, G P C; Zanotelli, M L; Gleisner, A L M; de Mello Brandão, A; Marroni, C A

    2006-04-01

    Mycophenolate sodium (EC-MPS) has been shown to be as effective and as safe as mycophenolate mofetil (MMF) in renal transplant patients. Nevertheless, compared to MMF its use in liver transplant patients has been limited. The purpose of this study was to analyze the efficacy of EC-MPS as a primary immunosuppressant or as a replacement for MMF in liver transplant patients. Ninety among 470 liver transplant recipients were receiving or had added an antimetabolite to their immunosuppressant therapy. The most common reason for this change was renal dysfunction (47.8%) or diabetes (32.2%). EC-MPS was started at a median of 30 months after liver transplantation. The mean administered daily dose was 720 mg/d. At least one gastrointestinal symptom was reported by 25 patients. Abdominal pain (16.6%) and diarrhea (14.5%) were the most frequent. EC-MPS had to be discontinued in two patients, while six others required dose reduction to resolve the symptoms. Hematological adverse events were infrequent: three patients had leukopenia and one, anemia, all of which responded to dosage reduction. There was a creatinine reduction within 6 months of drug commencement and maintenance of the lower creatinine levels at 1 year among patients who began EC-MPS for renal dysfunction. Serum low-density lipoprotein cholesterol and triglyceride levels were significantly lower among patients on EC-MPS than on MMF. In conclusion, EC-MPS appears to have a similar efficacy and safety profile as MMF in liver transplant patients. Hematological and gastrointestinal adverse events were infrequent; seldom had the drug to be discontinued.

  10. De novo Renal Transplantation after Kaposi Sarcoma: Favorable Outcome in a Patient Receiving Sirolimus and Mycophenolate-Based Immunosuppression

    Directory of Open Access Journals (Sweden)

    F. Friedersdorff

    2010-04-01

    Full Text Available Immunosuppressive treatment increases the risk of infection and malignancy in organ transplant recipients. We report on a 42-year-old male renal transplant recipient who lost his first graft after reduction of immunosuppressive treatment due to Kaposi sarcoma and who successfully underwent a second renal transplant 10 years later. The patient’s current treatment consists of low-dose prednisone, and the two antiproliferative immunosuppressants mycophenolate mofetil and rapamycin. 4.5 years after his second transplant, the serum creatinine is 1 mg/dl and the patient has no signs of recurrent disease.

  11. A longitudinal assessment of adherence with immunosuppressive therapy following kidney transplantation from the Mycophenolic Acid Observational REnal Transplant (MORE) study.

    Science.gov (United States)

    Tsapepas, Demetra; Langone, Anthony; Chan, Laurence; Wiland, Anne; McCague, Kevin; Chisholm-Burns, Marie

    2014-04-17

    Nonadherence with immunosuppressive therapy after renal transplantation is a major clinical concern, but longitudinal data are sparse. Adherence data were recorded during the Mycophenolic Acid Observational REnal Transplant (MORE) study to help inform compliance management decisions. Prospective data were analyzed from the four-year, observational MORE study of de novo adult renal transplant recipients receiving mycophenolic acid (MPA) as enteric-coated mycophenolate sodium (EC-MPS) or mycophenolate mofetil (MMF) at 40 US sites under routine management. Adherence was assessed using the Immunosuppressant Therapy Adherence Scale (ITAS): total score 0-12 (12, adherence; adherent recipients (p=0.59); graft loss was 4.7% (19/402) vs. 3.0% (12/406) (p=0.20); death was 1.5% (6/402) vs. 4.7% (19/406) (p=0.013). Adherence to the immunosuppressive regimen decreases over time, highlighting the need to monitor and encourage adherence even in long-term maintenance kidney transplant patients. Other than African American race, demographic factors may be of limited value in predicting nonadherence.

  12. Desenvolvimento de comprimidos de AAS 500 mg: influência do Amido 1500® na compressão direta Development of AAS 500 mg tablets influenced by direct compression (CD process

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    Osvaldo Albuquerque Cavalcanti

    2002-04-01

    Full Text Available O experimento teve por objetivo demonstrar a viabilidade tecnológica do desenvolvimento de comprimidos de AAS 500 mg (Ácido Acetil Salicílico, empregando processo de compressão direta (CD. O Amido 1500® foi usado como excipiente no desenvolvimento das formulações, visando investigar suas propriedades de compressibilidade, desintegração, agregação e lubrificação. Usando metodologias previstas em Farmacopéias, foram realizados ensaios tecnológicos e físico-químicos. Os resultados evidenciaram que a mistura dos pós apresentou características de fluxo e compressibilidade adequadas ao rol de excipientes para compressão direta disponíveis no mercado. A presença do Amido 1500® também interferiu no tempo de desintegração. Dentre as formulações propostas neste trabalho, a fórmula contendo 6,35% de Amido 1500® foi eleita a mais adequada por apresentar maior proximidade em relação aos produtos disponíveis no mercado brasileiroThe present work aims to show the technologic viability in the development of AAS 500 mg tablets using direct compression (CD process. We employed Starch 1500® as excipient to develop the formulations, trying to investigate its compression, disintegration, aggregation and lubrication properties. Technologic, physical and chemical essays were performed using methodologies anticipated in pharmacology. Results demonstrated that the powder mix showed characteristics of free flux and good compression qualities very important for the excipients of direct compression in the market. Starch 1500® interfered in the disintegration time. The formulation with 6,35% of Starch 1500® proposed in this work obtained a highest proximity between the products in the Brazilian market

  13. Mycophenolate

    Science.gov (United States)

    ... your muscles; confusion or difficulty thinking clearly; unsteadiness; memory loss; difficulty speaking or understanding what others say; ... is important to keep all medication out of sight and reach of children as many containers (such ...

  14. Mycophenolic acid inhibits migration and invasion of gastric cancer cells via multiple molecular pathways.

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    Boying Dun

    Full Text Available Mycophenolic acid (MPA is the metabolized product and active element of mycophenolate mofetil (MMF that has been widely used for the prevention of acute graft rejection. MPA potently inhibits inosine monophosphate dehydrogenase (IMPDH that is up-regulated in many tumors and MPA is known to inhibit cancer cell proliferation as well as fibroblast and endothelial cell migration. In this study, we demonstrated for the first time MPA's antimigratory and anti-invasion abilities of MPA-sensitive AGS (gastric cancer cells. Genome-wide expression analyses using Illumina whole genome microarrays identified 50 genes with ≥2 fold changes and 15 genes with > 4 fold alterations and multiple molecular pathways implicated in cell migration. Real-time RT-PCR analyses of selected genes also confirmed the expression differences. Furthermore, targeted proteomic analyses identified several proteins altered by MPA treatment. Our results indicate that MPA modulates gastric cancer cell migration through down-regulation of a large number of genes (PRKCA, DOCK1, INF2, HSPA5, LRP8 and PDGFRA and proteins (PRKCA, AKT, SRC, CD147 and MMP1 with promigratory functions as well as up-regulation of a number of genes with antimigratory functions (ATF3, SMAD3, CITED2 and CEAMCAM1. However, a few genes that may promote migration (CYR61 and NOS3 were up-regulated. Therefore, MPA's overall antimigratory role on cancer cells reflects a balance between promigratory and antimigratory signals influenced by MPA treatment.

  15. Risk evaluation and mitigation strategies: a focus on the mycophenolic acid preparations.

    Science.gov (United States)

    Rostas, Sara; Kim, Miae; Gabardi, Steven

    2014-03-01

    To review risks associated with mycophenolic acid (MPA) preparations and evaluate their required risk evaluation and mitigation strategies (REMS) elements. Articles were identified through a non-date-limited MEDLINE and EMBASE search using the terms fetal toxicity, teratogenicity, risk evaluation and mitigation strategies, REMS, MPA, mycophenolate mofetil, entericcoated MPA, and organ transplant. Information from the Food and Drug Administration (FDA) and the manufacturers of the MPA preparations was also evaluated. The MPA preparations are associated with several potential risks, including gastrointestinal disturbances and myelosuppression; however, their impact on the fetus in pregnant patients taking 1 of these agents poses the greatest risk. The FDA approved REMS programs for all MPA products, both innovator and generic preparations, in September 2012. With evidence of increased risk of miscarriage and birth defects associated with MPA use, the FDA instituted a REMS program that contains both a medication guide and elements to assure safe use (ETASU). The medication guides for the MPA products, which were previously FDA approved, should continue to be distributed to patients who get either an initial prescription filled or a refill. The ETASU requires prescribers to complete training and obtain patient signatures on the Patient-Prescriber Acknowledgment Form. A single, national, voluntary pregnancy registry specific to this medication has been established, and pregnant patients should be encouraged to participate. Although the impact of the MPA REMS on clinical practice is not clear, it is a step toward increasing the understanding of fetal risks with MPA.

  16. The impact of everolimus versus mycophenolate on blood and lymphocyte cyclosporine exposure in heart-transplant recipients

    DEFF Research Database (Denmark)

    Gustafsson, Finn; Barth, David; Delgado, Diego H

    2009-01-01

    CsA C2 levels and blood CsA AUC(0-12) in groups of patients treated with MMF or everolimus (R(2) 0.93 and 0.96, respectively; P 2) = 0.98), there was poor correlation...... between whole-blood C2 and lymphocyte AUC(0-12) in patients treated with everolimus (R(2) = 0.24). CONCLUSION: Standard blood CsA levels accurately predict intralymphocytic exposure to CsA in patients concomitantly treated with MMF but not in patients treated with everolimus........ METHODS: Twelve-hour pharmacokinetic studies of whole-blood and intralymphocytic CsA concentrations were conducted in long-term heart-transplant recipients treated with mycophenolate mofetil (MMF) + CsA (n = 8) and everolimus + CsA (n = 9). RESULTS: There was a highly significant correlation between blood...

  17. Is There Evidence to Support Brand to Generic Interchange of the Mycophenolic Acid Products?

    Science.gov (United States)

    Phillips, Karen; Reddy, Prabashni; Gabardi, Steven

    2017-02-01

    The uptake of generic immunosuppressants lags comparatively to other drug classes, despite that the Food and Drug Administration (FDA) uses identical bioequivalence standards for all drugs. Transplant societies acknowledge the cost savings associated with generic immunosuppressants and support their use following heart, lung, kidney, or bone marrow transplantation. Seven studies of the pharmacokinetics or clinical efficacy of generic mycophenolate mofetil compared to the innovator product are published; all studies and products were ex-United States. Three studies did not demonstrate any pharmacokinetic differences between generic and innovator products in healthy subjects, achieving FDA bioequivalence requirements. Two studies in renal allograft recipients demonstrated no difference in area under the curves between generic and innovator products, and in one, the maximum concentration (Cmax) fell outside the FDA regulatory range. Two studies revealed no difference in acute organ rejection or graft function in renal allograft recipients. Patient surveys indicate that cost is a barrier to immunosuppressant adherence. Generics present a viable method to reduce costs to payers, patients, and health care systems. Adherence to immunosuppressants is crucial to prevent graft failure. An affordable regimen potentially confers greater adherence. Concerns regarding the presumed inferiority of generic immunosuppressants should be assuaged by regulatory requirements for bioequivalency testing, transplant society position statements, and pharmacokinetic and clinical studies.

  18. Ensaio clinico com Teclozan: 500mg no tratamento da colite amebiana não disentérica. (Resultados com esquema terapêutico de 24 horas

    Directory of Open Access Journals (Sweden)

    Donald Huggins

    1978-12-01

    Full Text Available O Autor relata sua experiência com novo esquema terapêutico com Teclozan - dose total de 1.500mg empregada em 24 horas, em 40 pacientes portadores de colite amebiana não disentérica na Disciplina de Doenças Infecciosas e Parasitárias da Universidade Federal de Pernambuco. Após um controle de cura realizado no 4º, 8º, 12º e 20º dias após o tratamento, obteve eficácia em 75% dos enfermos (30 casos e excelente tolerância.

  19. Desarrollo y producción de cefazolina 500 mg y 1 g, polvo estéril para inyección

    Directory of Open Access Journals (Sweden)

    María Antonia Serrate Merino

    1998-12-01

    Full Text Available Se describe el desarrollo de la formulación para la obtención de cefazolina 500 mg y 1 g, polvo estéril para inyección, con la calidad requerida, así como el estudio de estabilidad para determinar su vida útil, tanto en forma de polvo como después de reconstituida. Se desarrolló este medicamento con calidad similar a las firmas internacionales al contar con la infraestructura necesaria, el personal técnico calificado y la posibilidad de adquirir la materia prima, además de reducir los costos, lo que garantiza un gran beneficio social y económico.The development of the formulation for obtaining 500 mg and 1 mg quality cefazolin, sterile powder for injection, together with the stability studies to determine this drug lifetime cither as powder or as reconstituted substance are described. The quality of the drug obtained was similar to that stated by the international manufacturers since the necessary infrastructure, required skilled personnel, adequate supply of raw material and reduced costs were assured. All this guarantees a great social and economic benefit.

  20. Average bioequivalence of single 500 mg doses of two oral formulations of levofloxacin: a randomized, open-label, two-period crossover study in healthy adult Brazilian volunteers

    Directory of Open Access Journals (Sweden)

    Eunice Kazue Kano

    2015-03-01

    Full Text Available Average bioequivalence of two 500 mg levofloxacin formulations available in Brazil, Tavanic(c (Sanofi-Aventis Farmacêutica Ltda, Brazil, reference product and Levaquin(c (Janssen-Cilag Farmacêutica Ltda, Brazil, test product was evaluated by means of a randomized, open-label, 2-way crossover study performed in 26 healthy Brazilian volunteers under fasting conditions. A single dose of 500 mg levofloxacin tablets was orally administered, and blood samples were collected over a period of 48 hours. Levofloxacin plasmatic concentrations were determined using a validated HPLC method. Pharmacokinetic parameters Cmax, Tmax, Kel, T1/2el, AUC0-t and AUC0-inf were calculated using noncompartmental analysis. Bioequivalence was determined by calculating 90% confidence intervals (90% CI for the ratio of Cmax, AUC0-t and AUC0-inf values for test and reference products, using logarithmic transformed data. Tolerability was assessed by monitoring vital signs and laboratory analysis results, by subject interviews and by spontaneous report of adverse events. 90% CIs for Cmax, AUC0-t and AUC0-inf were 92.1% - 108.2%, 90.7% - 98.0%, and 94.8% - 100.0%, respectively. Observed adverse events were nausea and headache. It was concluded that Tavanic(c and Levaquin(c are bioequivalent, since 90% CIs are within the 80% - 125% interval proposed by regulatory agencies.

  1. Ensaio clinico com Teclozan: 500mg no tratamento da colite amebiana não disentérica. (Resultados com esquema terapêutico de 24 horas

    Directory of Open Access Journals (Sweden)

    Donald Huggins

    1978-12-01

    Full Text Available O Autor relata sua experiência com novo esquema terapêutico com Teclozan - dose total de 1.500mg empregada em 24 horas, em 40 pacientes portadores de colite amebiana não disentérica na Disciplina de Doenças Infecciosas e Parasitárias da Universidade Federal de Pernambuco. Após um controle de cura realizado no 4º, 8º, 12º e 20º dias após o tratamento, obteve eficácia em 75% dos enfermos (30 casos e excelente tolerância.The author report his experience with Teclozine in the treatment on 40 patients suffering chronic intestinal amebiasis, employing a new therapeutical schedule - 1,500 mg as the total dose, within the period of 24 hours. After a follow-up on the 4th, 8th, 12th, and 20th days of treatment, the parasitological cure rate obtained was 75% (30 cases, and the drug was very well tolerated by all the patients.

  2. Effect of bovine somatotropin (500 mg) administered at ten-day intervals on ovulatory responses, expression of estrus, and fertility in dairy cows.

    Science.gov (United States)

    Rivera, F; Narciso, C; Oliveira, R; Cerri, R L A; Correa-Calderón, A; Chebel, R C; Santos, J E P

    2010-04-01

    The objectives of this study were to evaluate the effect of administering 500 mg of recombinant bovine somatotropin (bST) every 10 d on ovulatory responses, estrous behavior, and fertility of lactating Holstein cows. Lactating dairy cows were assigned to 1 of 2 treatments: a control with no administration of bST (73 primiparous and 120 multiparous cows) or 6 consecutive administrations of 500 mg of bST (83 primiparous and 123 multiparous cows) given subcutaneously at 10-d intervals starting 61+/-3 d postpartum (study d 0), concurrent with the initiation of the timed artificial insemination (AI). Blood samples were collected thrice weekly from 61+/-3 to 124+/-3 d in milk (DIM), and plasma samples were analyzed for concentrations of estradiol, glucose, insulin, insulin-like growth factor 1, and progesterone. The estrous cycle of cows was presynchronized with 2 injections of PGF(2alpha) at 37+/-3 and 51+/-3 DIM, and the Ovsynch timed AI protocol was initiated at 61+/-3 DIM. Ovaries were scanned to determine ovulatory responses during the Ovsynch protocol. Pregnancy was diagnosed at 33 and 66 d after AI. Body condition was scored on study d 0, 10, 42, and 76. Sixty-four cows were fitted with a pressure mounting sensor with radiotelemetric transmitters to monitor estrous behavior. Treatment of lactating dairy cows with 500 mg of bST at 10-d intervals increased yields of milk and milk components in the first 2 mo after treatment. Body condition of bST-treated cows remained unaltered, whereas control cows gained BCS. Treatment with bST increased concentrations of insulin-like growth factor 1 chronically, but concentrations of insulin and glucose increased only transiently in the first 7 d after the first injection of bST. Concentrations of progesterone during and after the Ovsynch protocol remained unaltered after treatment with bST; likewise, ovulatory responses during the Ovsynch protocol were mostly unaltered by treatment. Concentration of estradiol tended to be

  3. Desarrollo tecnológico de la formulación de cápsulas de ampicilina 250 y 500 mg

    Directory of Open Access Journals (Sweden)

    María Antonia Serrate

    1997-08-01

    Full Text Available Se describió el desarrollo tecnológico para la formulación de cápsulas de ampicilina trihidratada, reutilizando los finos que se obtienen de la tecnología por vía seca y que representan el 30 % de ésta. Se utilizó la vía húmeda por las características del fino obtenido y se logró un producto actualizado y con las características adecuadas para su uso. Las cápsulas de 250 y 500 mg fueron sometidas a estudio de estabilidad a temperaturas controladas y se determinaron las características físicoquímicas que debe cumplir el granulado. Esta reutilización de los finos, producto de la vía seca, logra un aprovechamiento óptimo de la materia prima que se dedica a esta producción.The technological development to produce the formulation of capsules of ampicillin trihydrate using again the products obtained through the dry procedure representing the 30 % of it, is described. A wet procedure was used because of the characteristics of the powder obtained and a current product was obtained having the proper characteristics for its use. Capsules of 250 and 500 mg were subjected to stability studies at controlled temperature and the physical and chemical characteristics that may comply with the granulate were also determined. This reutilization of fine products through the dry procedure makes it possible to attain an optimun use of the raw material employed for this production.

  4. Clinical efficacy and safety of a new 1000-mg suspension versus twice-daily 500-mg tablets of MPFF in patients with symptomatic chronic venous disorders: a randomized controlled trial.

    Science.gov (United States)

    Carpentier, Patrick; van Bellen, Bonno; Karetova, Debora; Hanafiah, Harunarashid; Enriquez-Vega, Elizabeth; Kirienko, Alexander; Dzupina, Andrej; Sabovic, Miso; Reina Gutierrez, Lourdes; Subwongcharoen, Somboom; Tüzün, Hasan; Maggioli, Arnaud

    2017-10-01

    Chronic venous disorders (CVD) is estimated to affect 30% to 50% of women and 10% to 30% of men. The most widely prescribed treatment for CVD worldwide is micronized purified flavonoid fraction 500 mg (MPFF). The aim of this clinical trial was to develop a new once daily 1000-mg oral suspension of MPFF. In an international, randomized, double-blind, parallel-group study, symptomatic individuals classified CEAP C0s to C4s were randomized in either treatment arm and treated for 8 weeks. Lower limb symptoms (discomfort, pain and heaviness) were assessed using Visual Analog Scales (VAS), and quality of life (QoL) was measured with the CIVIQ-20 Questionnaire. A total of 1139 patients were included in the study. Both MPFF treatment regimens were well tolerated and associated with a significant reduction in lower limb symptoms. A non-inferiority of MPFF 1000-mg oral suspension once daily compared to MPFF 500-mg tablet twice daily (P1000 mg and -3.37 cm for MPFF 500 mg), leg pain (-3.27 cm for MPFF 1000 mg and -3.31 cm for MPFF 500 mg) and leg heaviness (-3.41 cm for MPFF 1000 mg and -3.46 cm for MPFF 500 mg). The patients' QoL was improved by about 20 points on the CIVIQ scale in both groups (19.33 points for MPFF 1000 mg and 20.28 points for MPFF 500 mg). MPFF 1000-mg oral suspension and MPFF 500-mg tablets treatments were associated with similar reductions in lower limb symptoms and QoL improvement. The new once daily MPFF1000-mg oral suspension has a similar safety profile to two tablets of MPFF 500 mg, with the advantage of one daily intake, potentially associated with improved patient adherence and easier CVD management.

  5. Comparison of 3 estimation methods of mycophenolic acid AUC based on a limited sampling strategy in renal transplant patients.

    Science.gov (United States)

    Hulin, Anne; Blanchet, Benoît; Audard, Vincent; Barau, Caroline; Furlan, Valérie; Durrbach, Antoine; Taïeb, Fabrice; Lang, Philippe; Grimbert, Philippe; Tod, Michel

    2009-04-01

    A significant relationship between mycophenolic acid (MPA) area under the plasma concentration-time curve (AUC) and the risk for rejection has been reported. Based on 3 concentration measurements, 3 approaches have been proposed for the estimation of MPA AUC, involving either a multilinear regression approach model (MLRA) or a Bayesian estimation using either gamma absorption or zero-order absorption population models. The aim of the study was to compare the 3 approaches for the estimation of MPA AUC in 150 renal transplant patients treated with mycophenolate mofetil and tacrolimus. The population parameters were determined in 77 patients (learning study). The AUC estimation methods were compared in the learning population and in 73 patients from another center (validation study). In the latter study, the reference AUCs were estimated by the trapezoidal rule on 8 measurements. MPA concentrations were measured by liquid chromatography. The gamma absorption model gave the best fit. In the learning study, the AUCs estimated by both Bayesian methods were very similar, whereas the multilinear approach was highly correlated but yielded estimates about 20% lower than Bayesian methods. This resulted in dosing recommendations differing by 250 mg/12 h or more in 27% of cases. In the validation study, AUC estimates based on the Bayesian method with gamma absorption model and multilinear regression approach model were, respectively, 12% higher and 7% lower than the reference values. To conclude, the bicompartmental model with gamma absorption rate gave the best fit. The 3 AUC estimation methods are highly correlated but not concordant. For a given patient, the same estimation method should always be used.

  6. Different flavonoids present in the micronized purified flavonoid fraction (Daflon 500 mg) contribute to its anti-hyperpermeability effect in the hamster cheek pouch microcirculation.

    Science.gov (United States)

    Paysant, J; Sansilvestri-Morel, P; Bouskela, E; Verbeuren, T J

    2008-02-01

    This study evaluated microcirculatory effects of the flavonoid substances that constitute the micronized purified flavonoid fraction (MPFF) (Daflon 500 mg) in comparison to diosmin. In groups of 3 male hamsters, oral treatment with MPFF or diosmin (15 min before anesthesia) did not alter blood pressure. At 10 or 30 mg/kg, both MPFF and diosmin significantly decreased the leaky sites caused by ischemia/reperfusion (I/R) (30 min) in the hamster cheek pouch; the effect was significantly higher with MPFF (39+/-1% and 52+/-1%, respectively) than diosmin (18+/-1% and 37+/-3%, respectively). Eight groups of 3 hamsters each were treated with the components of MPFF. Diosmetin only decreased the number leaky sites at 30 mg/kg (decrease: 15+/-2%). The decrement at 10 and 30 mg/kg averaged at: 17+/-3% and 44+/-1%, respectively, for hesperidin; 19+/-1% and 46+/-2%, respectively, for linarin; and 30+/-1% and 44+/-1%, respectively, for isorhoifolin. Hesperidin, linarin, and isorhoifolin each displayed an anti-leakage effect comparable to or greater than diosmin. MPFF decreases permeability more than any of its single constituents, suggesting that the flavonoids present in its formulation have a synergistic action. These results illustrate that MPFF is more potent than single diosmin in this model of hyperpermeability and that each of the flavonoid substances present in MPFF contribute to its action.

  7. Micophenolat Mofetil Versus Azathioprine: Effects on Renal Graft Function in Early Posttransplant Period

    Directory of Open Access Journals (Sweden)

    Farid Ljuca

    2009-05-01

    Full Text Available All conventional immunosuppressive tree drugs-protocols are based on Cyclosporine; consisting of low doses of Cyclosporine (CsA, Azathioprine (AZA or Mycophenolate Mofetil (MMF and Prednisolone, AZA has been used in clinical transplantation for more than 30 years and was the first immunosuppres-sive agent to achieve widespread use in organ transplantation. MMF was introduced in clinical practice in 1995 after several clinical trials proved that it was more efficient than AZA for prevention of acute rejection episodes. Our aim was to evaluate influence of AZA and MMF on renal graft function in early post-transplant stage. Study recruited 74 patients who underwent kidney transplantation in University Clinical Centre Tuzla. All patients received CsA and corticosteroid-based immunosuppression, as a part of triple immunosuppressive regiment, 40 patients received AZA and 34 MMF. In order to assess renal graft function, following parameters were evaluated: glomerular filtration rate GFR (ml/min creatinine clearance (CrCl (ml/min, 24 h urine output (ml/day, and from the serum potassium, sodium, urea and creatinine (mmol/dm3. Significantly higher average values of 24 hour urine output were recorded during first seven postoperative days in patients receiving MMF compared to those treated with AZA. Serum creatinine values showed statistically significant decrease, starting with the second postoperative day, in MMF vs. AZA group (168,7±70,5 vs. 119,9±42,6; p<0,0007. GFR was significantly higher in MMF compared to the AZA group of patients. On the first post-transplant day CrCl was higher in AZA group (24,3±10 vs. 17,5±7,3; p=0,01, next six days situation is reversed CrCl is significantly higher in the MMF group (43,7±15 vs. 53, 4±22, 8 p=0,006. MMF vs. AZA therapy was associated with protective effect against worsening of renal function in first seven post-transplant days.

  8. USE OF MYCOPHENOLATE MOPHETYL IN PATIENT WITH SYSTEMIC LUPUS ERYTHEMATOSUS

    Directory of Open Access Journals (Sweden)

    S.I. Valiyeva,

    2006-01-01

    Full Text Available The article reports a case of highly active SLE and lupusbnephritis in a 15 years old boy, who was treated with mycophenolate mophetyl the case was notable for high activity and aggressive course of the disease with rapid development of renal unsufficiency, polyorganic unsufficiency and antiphospholipid syndrome. Although the patient received an appropriate active therapy, including synchronized therapy (consisting of timebrelated plasmopherresis and infusions of cyclophosphamide and metyl prednisolone, glucocorticoides, preparations improving blood circulation (pentoxyphillin, dipiridamol, heparine, intravenous immunoglobulins, the disease activity control was unsufficient. The administration of mycophenolate mophetyl has led to diminuition of the disease activity, which was registered at the end of the second week of treatment, and finally has reached a level of clinical and laboratoty remission of the disease.Key words: systemic lupus erythematosus, mycophenolate mophetyl, children, treatment.

  9. Relative bioavailability of generic and branded 250-mg and 500-mg oral chlorphenesin carbamate tablets in healthy Korean volunteers: a single-dose, randomized-sequence, open-label, two-period crossover trial.

    Science.gov (United States)

    Yu, Ji-young; Song, Hyun Ho; Kim, Bo Gyeom; Park, Hyeon Ju; Choi, Kwang Sik; Kwon, Young Ee

    2009-11-01

    Chlorphenesin carbamate is a skeletal muscle relaxant approved in Korea for use in the treatment of pain and discomfort related to skeletal muscle trauma and inflammation. The aim of this study was to assess the bioequivalence of a generic formulation of chlorphenesin carbamate at doses of 250 and 500 mg and 2 branded formulations of the same doses in healthy Korean adults. This single-dose, randomized-sequence, open-label, 2-period crossover study was conducted in healthy Korean male and female volunteers. Subjects were assigned to receive, in a randomized sequence, a single dose of the generic (test) and branded (reference) formulations of chlorphenesin carbamate at a dose of 250 or 500 mg. Blood samples were drawn at 0, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 9, 12, and 15 hours after administration. Pharmacokinetic properties (C(max), T(max), AUC(0-t) AUC(0-infinity), t(1/2), and ke) were determined using HPLC. The formulations were to be considered bioequivalent if the 90% CIs of the treatment ratios of the geometric means of C(max) and AUC(0-t) were within a predetermined range of log 0.80 to log 1.25 based on regulatory criteria. Tolerability was assessed by monitoring for adverse events (AEs) on physical examination and/or e-mail and personal interview at the beginning and end of each study period. Twenty-eight subjects (22 men, 6 women) received chlorphenesin carbamate at the 250-mg dose, and 24 male subjects received the 500-mg dose. The mean (SD) ages of the subjects were 24.0 (2.6) and 24.0 (1.9) years in the 250- and 500-mg groups, respectively. No significant differences were found between the test and reference formulations (90% CIs: C(max), 1.0048-1.1153 with the 250-mg dose and 0.9630-1.1189 with the 500-mg dose; AUC(0-t), 0.9882-1.0546 and 0.9842-1.0578, respectively). No clinically significant AEs (upper gastric pain, abdominal bloating, pyrexia, edema, nausea, heartburn, constipation, headache, dizziness, drowsiness, or fatigue) were reported throughout

  10. Limited sampling strategies drawn within 3 hours postdose poorly predict mycophenolic acid area-under-the-curve after enteric-coated mycophenolate sodium.

    NARCIS (Netherlands)

    Winter, B.C. de; Gelder, T. van; Mathôt, R.A.A.; Glander, P.; Tedesco-Silva, H.; Hilbrands, L.B.; Budde, K.; Hest, R.M. van

    2009-01-01

    Previous studies predicted that limited sampling strategies (LSS) for estimation of mycophenolic acid (MPA) area-under-the-curve (AUC(0-12)) after ingestion of enteric-coated mycophenolate sodium (EC-MPS) using a clinically feasible sampling scheme may have poor predictive performance. Failure of

  11. GINGIVAL OVERGROWTH INDUCED BY IMMUNOSUPPRESSIVE TREATMENT WITH CYCLOSPORINE A AND MYCOPHENOLATE MOFETIL IN A PATIENT WITH KIDNEY TRANSPLANT – A CASE REPORT AND LITERATURE REVIEW

    Directory of Open Access Journals (Sweden)

    Daniela Trandafir

    2013-07-01

    Full Text Available Cyclosporine A, a drug that inhibits the immuneresponse, has been widely used for over 30 years in immunosuppressivetherapy protocols for patient‑recipients ofthe transplanted organs. One of the commonly reportedside effects of Cyclosporine A is gingival overgrowth, withvarying degrees of severity, which may interfere with theaesthetics and normal functions of the oral cavity. Combinationwith other drugs that can recognize the gum tissueas a secondary target organ increases the risk ofdrug‑induced gingival overgrowth. In cases where a lowerdose of Cyclosporine A or conversion to another immunosuppressiveagent (a drug not assigned to such a sideeffect are not possible, the management of severe gingivalovergrowth focuses on surgical excision of the excessivelyproliferated gingival tissue. We report the case of a youngadult with moderate drug‑induced gingival overgrowth,the beneficiary of a functional transplanted kidney about9 years ago, treated with two immunosuppressives, whohas undergone gingivectomy with electrocautery, as a necessaryintervention to improve the oral hygiene and toavoid worsening of malfunctions in the oral cavity.

  12. Preventing acute rejection, Epstein-Barr virus infection, and posttransplant lymphoproliferative disorders after kidney transplantation: Use of aciclovir and mycophenolate mofetil in a steroid-free immunosuppressive protocol

    DEFF Research Database (Denmark)

    Birkeland, S.A.; Andersen, H.K.; Hamilton-Dutoit, Stephen Jacques

    1999-01-01

    Background: A widely held view is that any increase in the potency of an immunosuppressive agent will lead to an increase in infection and malignancy, such as life-threatening Epstein-Barr virus (EBV) induced posttransplant lymphoproliferative disorders (PTLD), We tested this paradigm by studying...... or reactivated EBV infection (PREBV) was correlated to acute rejection (treated with OKT3; Pdisease is included); (2) aciclovir protected against PREBV (P

  13. Total-Body Irradiation Followed By Cyclosporine and Mycophenolate Mofetil in Treating Patients With Severe Combined Immunodeficiency Undergoing Donor Bone Marrow Transplant

    Science.gov (United States)

    2017-07-12

    Adenosine Deaminase Deficiency; Autosomal Recessive Disorder; Immune System Disorder; Purine-Nucleoside Phosphorylase Deficiency; Severe Combined Immunodeficiency; Severe Combined Immunodeficiency With Absence of T and B Cells; X-Linked Severe Combined Immunodeficiency

  14. Mycophenolate fetal toxicity and risk evaluation and mitigation strategies.

    Science.gov (United States)

    Kim, M; Rostas, S; Gabardi, S

    2013-06-01

    The mycophenolic acid (MPA) preparations are one of the most commonly used immunosuppressants in the United States. However, these agents carry a black box warning regarding their use during pregnancy due to an association with increased risk of miscarriage and congenital defects. To ensure that the benefits of MPA outweigh the risks, the Food and Drug Administration (FDA) required all manufacturers of MPA products to propose risk evaluation and mitigation strategies (REMS). Four years after initially calling for proposals, the FDA approved a single shared REMS system in September 2012. The elements of the MPA REMS include a medication guide and elements to assure safe use (ETASU). The medication guide, which was previously FDA-approved in 2008, should continue to be distributed to patients, and the ETASU requires physicians to complete training and obtain patient signatures on the "Patient-Prescriber Acknowledgement Form." A single, national, voluntary pregnancy registry is available, and pregnant patients should be encouraged to participate. Although the impact of the MPA REMS on clinical practice is not clear, it is a step toward increasing the understanding of fetal risks with MPA products among patients and possibly practitioners. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

  15. Effects of food on the pharmacokinetics of gemigliptin/metformin sustained-release 50/1,000 mg (25/500 mg x 2 tablets) fixeddose combination tablet in healthy male volunteers.

    Science.gov (United States)

    Choi, Hee Youn; Noh, Yook-Hwan; Kim, Yo Han; Kim, Mi Jo; Lee, Shi Hyang; Kim, Jeong-Ae; Kim, Bogyeong; Lim, Hyeong-Seok; Bae, Kyun-Seop

    2014-05-01

    For patient convenience, a gemigliptin/metformin sustainedrelease fixed-dose combination (FDC) tablet was developed. This study was conducted to investigate the effects of food on the pharmacokinetic (PK) profile of the FDC tablets. This was an open-label, randomized, single dose, 2-period, 2-sequence crossover study in 24 healthy male volunteers. The FDC tablets (25/500 mg × 2 tablets) were administered in high-fat fed and fasted states on separate occasions, and each subject was randomly allocated to each sequence with a 7-day washout period. PK blood samplings were conducted from predose to 48 hours after dosing. Tolerability assessments were performed throughout the study. Nine adverse events (AEs) of mild intensity were reported from 8 subjects after study drug administration, and the AE frequency was similar between treatments. No serious AEs were reported. The PK parameters of gemigliptin and metformin were compared between fasting and fed states. For gemigliptin, the geometric mean ratios (GMRs) (fed : fasted state) of the Cmax and AUClast were 0.886 (90% confidence interval (CI) 0.781 - 1.006) and 1.021 (90% CI 0.949 - 1.099), respectively. For metformin, the GMRs of the Cmax and AUClast were 0.811 (90% CI 0.712 - 0.923) and 1.144 (90% CI 1.013 - 1.291), respectively. A prolonged tmax for metformin was observed. These results are similar to the effects of food on each component. The FDC tablet may have a similar PK profile as that of individual drugs and is generally tolerable when administered with food. These results indicate that the FDC tablet can be administered in the same dosing regimen as each component, especially that of metformin sustained-release.

  16. Maximum a posteriori Bayesian estimation of mycophenolic Acid area under the concentration-time curve: is this clinically useful for dosage prediction yet?

    Science.gov (United States)

    Staatz, Christine E; Tett, Susan E

    2011-12-01

    This review seeks to summarize the available data about Bayesian estimation of area under the plasma concentration-time curve (AUC) and dosage prediction for mycophenolic acid (MPA) and evaluate whether sufficient evidence is available for routine use of Bayesian dosage prediction in clinical practice. A literature search identified 14 studies that assessed the predictive performance of maximum a posteriori Bayesian estimation of MPA AUC and one report that retrospectively evaluated how closely dosage recommendations based on Bayesian forecasting achieved targeted MPA exposure. Studies to date have mostly been undertaken in renal transplant recipients, with limited investigation in patients treated with MPA for autoimmune disease or haematopoietic stem cell transplantation. All of these studies have involved use of the mycophenolate mofetil (MMF) formulation of MPA, rather than the enteric-coated mycophenolate sodium (EC-MPS) formulation. Bias associated with estimation of MPA AUC using Bayesian forecasting was generally less than 10%. However some difficulties with imprecision was evident, with values ranging from 4% to 34% (based on estimation involving two or more concentration measurements). Evaluation of whether MPA dosing decisions based on Bayesian forecasting (by the free website service https://pharmaco.chu-limoges.fr) achieved target drug exposure has only been undertaken once. When MMF dosage recommendations were applied by clinicians, a higher proportion (72-80%) of subsequent estimated MPA AUC values were within the 30-60 mg · h/L target range, compared with when dosage recommendations were not followed (only 39-57% within target range). Such findings provide evidence that Bayesian dosage prediction is clinically useful for achieving target MPA AUC. This study, however, was retrospective and focussed only on adult renal transplant recipients. Furthermore, in this study, Bayesian-generated AUC estimations and dosage predictions were not compared

  17. Calcineurin inhibitor sparing with mycophenolate in kidney transplantation: a systematic review and meta-analysis.

    LENUS (Irish Health Repository)

    Moore, Jason

    2009-02-27

    Limiting the exposure of kidney transplant recipients to calcineurin inhibitors (CNIs) has potential merit, but there is no clear consensus on the utility of current strategies. In an attempt to aid clarification, we conducted a systematic review and meta-analysis of randomized trials that assessed CNI sparing (minimization or elimination) with mycophenolate as sole adjunctive immunosuppression.

  18. Production of Mycophenolic Acid by Penicillium brevicompactum Using Solid State Fermentation.

    Science.gov (United States)

    Patel, Gopal; Patil, Mahesh D; Soni, Surbhi; Chisti, Yusuf; Banerjee, Uttam Chand

    2017-05-01

    Solid-state fermentation using the microfungus Penicillium brevicompactum for the production of mycophenolic acid is reported in this paper. Of the initial substrates tested (whole wheat, cracked wheat, long grain Basmati rice, and short grain Parmal rice), Parmal rice proved to be the best. Under initial conditions, using steamed Parmal rice with 80% (w/w) initial moisture content, a maximum mycophenolic acid concentration of 3.4 g/kg substrate was achieved in 12 days of fermentation at 25 °C. The above substrate was supplemented with the following additional nutrients (g/L packed substrate): glucose 40.0, peptone 54.0, KH 2 PO 4 8.0, MgSO4⋅7H 2 O 2.0, glycine 7.0, and methionine 1.65 (initial pH 5.0). A small amount of a specified trace element solution was also added. The final mycophenolic acid concentration was increased to nearly 4 g/kg substrate by replacing glucose with molasses. Replacing Parmal rice with rice bran as substrate further improved the mycophenolic acid production to nearly 4.5 g/kg substrate.

  19. Simultaneous determination of ochratoxin A, mycophenolic acid and fumonisin B-2 in meat products

    DEFF Research Database (Denmark)

    Sørensen, Louise Marie; Mogensen, Jesper; Nielsen, Kristian Fog

    2010-01-01

    Here we present a method for simultaneous determination of the fungal metabolites mycophenolic acid, ochratoxin A (OTA) and fumonisin B-2 (FB2) in meat products. Extraction was performed with water-acetonitrile, followed by acetone-induced precipitation of salts and proteins. Purification...

  20. Consensus report on therapeutic drug monitoring of mycophenolic acid in solid organ transplantation

    NARCIS (Netherlands)

    D. Kuypers (Dirk); Y. le Meur (Yann); M. Cantarovich (Marcelo); M.J. Tredger (Michael); S.E. Tett (Susan); D. Cattaneo (Dario); B. Tönshoff (Burkhard); D.W. Holt (David); J. Chapman (Jeremy); T. van Gelder (Teun)

    2010-01-01

    textabstractWith the increasing use of mycophenolic acid (MPA) in solid organ transplantation, the need for more accurate drug dosing has become evident. Personalized immunosuppressive therapy requires better strategies for avoidance of drug-related toxicity while maintaining efficacy. Few studies

  1. Successful Treatment of Fibrosing Organising Pneumonia Causing Respiratory Failure with Mycophenolic Acid.

    Science.gov (United States)

    Paul, Christina; Lin-Shaw, Ammy; Joseph, Mariamma; Kwan, Keith; Sergiacomi, Gianluigi; Mura, Marco

    2016-01-01

    Organising pneumonia (OP) is usually promptly responsive to corticosteroid treatment. We describe a series of 3 cases of severe, progressive, biopsy-proven fibrosing OP causing respiratory failure. All cases presented with peribronchial and subpleural consolidations, had a fibro-inflammatory infiltrative component in the alveolar septa, and only had a partial and unsatisfactory response to corticosteroids. However, they responded to mycophenolic acid (MPA) treatment with resolution of respiratory failure as well as clinical and functional improvement. MPA as an additional treatment option for aggressive forms of fibrosing OP and interstitial lung disease needs to be further explored. © 2016 S. Karger AG, Basel.

  2. Do cytostatic drugs reach drinking water? The case of mycophenolic acid

    International Nuclear Information System (INIS)

    Franquet-Griell, Helena; Ventura, Francesc; Boleda, M.Rosa; Lacorte, Silvia

    2016-01-01

    Mycophenolic acid (MPA) has been identified as a new river contaminant according to its wide use and high predicted concentration. The aim of this study was to monitor the impact of MPA in a drinking water treatment plant (DWTP) that collects water downstream Llobregat River (NE Spain) in a highly densified urban area. During a one week survey MPA was recurrently detected in the DWTP intake (17–56.2 ng L"−"1). The presence of this compound in river water was associated to its widespread consumption (>2 tons in 2012 in Catalonia), high excretion rates and low degradability. The fate of MPA in waters at each treatment step of the DWTP was analyzed and complete removal was observed after pretreatment with chlorine dioxide. So far, MPA has not been described as water contaminant and its presence associated with its consumption in anticancer treatments is of relevance to highlight the importance of monitoring this compound. - Highlights: • MPA, a cytostatic drug, has been identified as a new river water contaminant. • MPA is eliminated during dioxychlorination in a drinking water treatment plant. • No residues of MPA were detected in finished drinking water. • Isotope dilution LC-MS/MS permitted the trace quantification of MPA in water. - Mycophenolic acid, a cytostatic drug, has been identified as a new river water contaminant and it is removed during purification in a Drinking Water Treatment Plant.

  3. Do cytostatic drugs reach drinking water? The case of mycophenolic acid.

    Science.gov (United States)

    Franquet-Griell, Helena; Ventura, Francesc; Boleda, M Rosa; Lacorte, Silvia

    2016-01-01

    Mycophenolic acid (MPA) has been identified as a new river contaminant according to its wide use and high predicted concentration. The aim of this study was to monitor the impact of MPA in a drinking water treatment plant (DWTP) that collects water downstream Llobregat River (NE Spain) in a highly densified urban area. During a one week survey MPA was recurrently detected in the DWTP intake (17-56.2 ng L(-1)). The presence of this compound in river water was associated to its widespread consumption (>2 tons in 2012 in Catalonia), high excretion rates and low degradability. The fate of MPA in waters at each treatment step of the DWTP was analyzed and complete removal was observed after pretreatment with chlorine dioxide. So far, MPA has not been described as water contaminant and its presence associated with its consumption in anticancer treatments is of relevance to highlight the importance of monitoring this compound. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Anti-Rhodotorula activity of mycophenolic acid enhanced in the presence of polyene antibiotic nystatin.

    Science.gov (United States)

    Kinoshita, H; Wongsuntornpoj, S; Ihara, F; Nihira, T

    2017-02-01

    Rhodotorula species are opportunistic pathogens, which cause not only systemic fungaemia but also other localized infections. Despite serious side effects such as nephrotoxicity and hypokalemia, amphotericin B (a polyene antifungal) has been commonly prescribed for Rhodotorula infection because Rhodotorula species are resistant against a candin family of antifungal agents. In this study, novel active compounds against Rhodotorula species were screened from the extracts of entomopathogenic fungi based on the synergistic effect of polyene nystatin (NYS), which causes efficient targeting of compounds due to increased permeability through the fungal cell membrane. Around 37% of culture extracts from 31 entomopathogenic fungal strains showed anti-Rhodotorula activity in the synergistic bioassay system, suggesting that the coexistence assay with NYS enhanced the discovery of anti-Rhodotorula compounds. Judging from various physicochemical data, the active component from strain HF763 was identified as an immunosuppressant drug, mycophenolic acid (MPA). The minimum inhibitory concentration of MPA against three pathogenic Rhodotorula strains was determined, focusing on the synergistic effect with NYS. The results revealed that the values decreased by at least 87% in the presence of NYS, indicating that MPA showed a synergistic effect with NYS. This study aimed to screen active compounds against Rhodotorula species that are resistant to a candin family of antifungal agents, from entomopathogenic fungi. Assuming that most of the latent antifungal compounds do not exert their activity due to their inability to penetrate the membrane, we took advantage of polyene nystatin in the screening to increase permeability through the fungal cell membrane. The result of the screening revealed hidden antifungal activity of mycophenolic acid, demonstrating that the method applied in this study unlocks the potentials of bioresources, and proposes a new remedy for mycosis. © 2016 The

  5. César Augusto Restrepo Valencia, Consuelo Vélez Álvarez Abstract Objective. To evaluate the effectiveness of calcineurin ciclosporin and tacrolimus inhibitors to induce remission in patients with refractory lupus nephritis. Patients, materials and methods. Patients with lupus nephritis class IV-G who despite receiving therapy with high doses of steroid and with a cytostatic (cyclophosphamide or mycophenolate for 3 months had not been able to induce some kind of remission.The exclusion criteria were creatinine levels greater than 3 mg / dl, pregnancy, previous history of exposure to calcineurin inhibitors, cancer, active infections, uncontrolled hypertension, and negligence with medication intake. The recommended dose of cyclosporine was 3 mg / kg / day and tacrolimus 0.1 mg / kg / day, in joint with prednisone 0.3 mg / kg / day, cyclophosphamide 1 mg / kg / day or mycophenolate mofetil 1 gram every 12 hours. The cyclophosphamide was administered only during 6 months, after which it was changed to azathioprine at doses of 1 mg / kg / day. Still, mycophenolate was continued at the same dose. All patients completed a minimum period of 12 months follow-up, it was considered that patients achieved partial remission when proteinuria decreased by 50% of the baseline value or its value decreased to less than 1 gram in 24 hours, decrease of leukocytes count and red blood cells in urine of 50%, and creatinine values were stable. A complete remission was considered when there was a reduction in proteinuria in a value less than 300 mg per 24 hours, urinary sediment with less than 3 red blood cells, less than 5 leukocyte for each high power microscopic field, and a creatinine value reduction by 50% or reaching a normal value. Results. Twelve patients met the inclusion criteria and initiated the calcineurin inhibitor protocol. Two presented accelerated deterioration in their function and required chronic dialysis therapy. Ten patients with active treatment completed 12 months

    Directory of Open Access Journals (Sweden)

    César Augusto Restrepo Valencia

    2014-10-01

    Full Text Available Objective: To evaluate the effectiveness of calcineurin ciclosporin and tacrolimus inhibitors to induce remission in patients with refractory lupus nephritis. Patients, materials and methods: Patients with lupus nephritis class IV-G who despite receiving the rapy with high doses of steroid and with a cytostatic (cyclophosphamide or mycophenolate for 3 months had not been able to induce some kind of remission.The exclusion criteria were creatinine levels greater than 3 mg / dl, pregnancy, previous history of exposure to calcineurin inhibitors, cancer, active infections, uncontrolled hypertension, and negligence with medication intake. The recommended dose of cyclosporine was 3 mg / kg / day and tacrolimus 0.1 mg / kg / day, in joint with prednisone 0.3 mg / kg / day, cyclophosphamide 1 mg / kg / day or mycophenolate mofetil 1 gram every 12 hours. The cyclophosphamide was administered only during 6 months, after which it was changed to azathioprine at doses of 1 mg / kg / day. Still, mycophenolate was continued at the same dose. All patients completed a minimum period of 12 months follow-up, it was considered that patients achieved partial remission when proteinuria decreased by 50% of the baseline value or its value decreased to less than 1 gram in 24 hours, decrease of leukocytes count and red blood cells in urine of 50%, and creatinine values were stable. A complete remission was considered when there was a reduction in proteinuria in a value less than 300 mg per 24 hours, urinary sediment with less than 3 red blood cells, less than 5 leukocyte for each high power microscopic field, and a creatinine value reduction by 50% or reaching a normal value. Results: Twelve patients met the inclusion criteria and initiated the calcineurin inhibitor protocol. Two presented accelerated deterioration in their function and required chronic dialysis therapy. Ten patients with active treatment completed 12 months of followup, of which 4 (40% had partial

  6. "Determination of mycophenolic acid in human plasma by high-performance liquid chromatography"

    Directory of Open Access Journals (Sweden)

    "Mehdi Ahadi Barzoki

    2005-05-01

    Full Text Available A simple, sensitive and reproducible HPLC method is presented for determination of mycophenolic acid(MPA in human plasma. Samples were prepared after precipitation of the plasma protein by addition of acetonitrile and naproxen was used as internal standard (I.S.. Separation was performed by reversedphase HPLC, using a Hamilton PRP-C18 Column, 51% acetonitrile and 49% potassium phosphate buffer (20 mM at pH 3.0 as mobile phase, flow rate of 1.0 ml/min, and UV detection at 215 nm. MPA and I.S. had retention times of 7.5 and 11.35 min, respectively. The method showed an acceptable linearity in the range of 0.1µg/ml-40µg/ml with r2 of .9992. The concentration of 0.1µg/ml was determined as quantification limit. Mean absolute recovery was 94.8%. The mean intra- and inter-day reproducibility of method was 4.6 and 11.4% respectively.

  7. The necrotic signal induced by mycophenolic acid overcomes apoptosis-resistance in tumor cells.

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    Gwendaline Guidicelli

    Full Text Available BACKGROUND: The amount of inosine monophosphate dehydrogenase (IMPDH, a pivotal enzyme for the biosynthesis of the guanosine tri-phosphate (GTP, is frequently increased in tumor cells. The anti-viral agent ribavirin and the immunosuppressant mycophenolic acid (MPA are potent inhibitors of IMPDH. We recently showed that IMPDH inhibition led to a necrotic signal requiring the activation of Cdc42. METHODOLOGY/PRINCIPAL FINDINGS: Herein, we strengthened the essential role played by this small GTPase in the necrotic signal by silencing Cdc42 and by the ectopic expression of a constitutive active mutant of Cdc42. Since resistance to apoptosis is an essential step for the tumorigenesis process, we next examined the effect of the MPA-mediated necrotic signal on different tumor cells demonstrating various mechanisms of resistance to apoptosis (Bcl2-, HSP70-, Lyn-, BCR-ABL-overexpressing cells. All tested cells remained sensitive to MPA-mediated necrotic signal. Furthermore, inhibition of IMPDH activity in Chronic Lymphocytic Leukemia cells was significantly more efficient at eliminating malignant cells than apoptotic inducers. CONCLUSIONS/SIGNIFICANCE: These findings indicate that necrosis and apoptosis are split signals that share few if any common hub of signaling. In addition, the necrotic signaling pathway induced by depletion of the cellular amount of GTP/GDP would be of great interest to eliminate apoptotic-resistant tumor cells.

  8. Mycophenolic acid suppresses human pterygium and normal tenon fibroblast proliferation in vitro.

    Science.gov (United States)

    Amer, Radgonde; Rabinowich, Liane; Maftsir, Genia; Puxeddu, Ilaria; Levi-Schaffer, Francesca; Solomon, Abraham

    2010-10-01

    To investigate whether mycophenolic acid (MPA) exerts antifibrotic effects on pterygium fibroblasts (PFB) with and without stimulation with fibrogenic cytokines, and to compare the efficacy of MPA with mitomycin (MMC) and dexamethasone (DXM) on PFB and tenon fibroblasts (TFB). TFB and PFB were obtained from tissue explants during strabismus or pterygium surgery. Proliferation of subconfluent fibroblasts ± basic fibroblast growth factor (bFGF) (10 ng/ml) was assessed by using the (3H) thymidine-incorporation assay. Cell cultures were incubated with MPA, MMC or DXM. Apoptosis was evaluated by quantifying Annexin V and propidium iodide positive cells with flow cytometry. MPA showed a concentration-dependent inhibition of proliferation of PFB ± bFGF as well as TFB ± bFGF. The antiproliferative effect of MPA was comparable with that of MMC and DXM. Short exposure of PFB to MPA under profibrogenic conditions was significantly inhibitory. No apoptotic effect was found on TFB. MPA suppressed tenon and pterygium fibroblast proliferation in vitro under basal and profibrogenic conditions. It was comparable with MMC under long-term exposure, but MMC was more suppressive under short-term exposure. MPA may be safer than MMC due to a more specific mechanism of action and lack of cytotoxicity. Further investigation is warranted regarding MPA concentrations that will lead to a potent antiproliferative effect in vivo.

  9. Mycophenolate sodium for the treatment of chronic non-infectious uveitis of childhood.

    Science.gov (United States)

    Doycheva, Deshka; Zierhut, Manfred; Blumenstock, Gunnar; Sobolewska, Bianka; Voykov, Bogomil; Hohmann, Johanna; Spitzer, Martin S; Deuter, Christoph

    2016-08-01

    To assess the efficacy and tolerability of mycophenolate sodium (MPS) in the therapy of children with chronic non-infectious uveitis. Retrospective analysis of 23 children with chronic uveitis, treated with MPS, with a follow-up of at least 6 months. The main outcome measures were time to uveitis reactivation and corticosteroid-sparing effect under MPS treatment. The secondary outcome measures were best-corrected visual acuity (BCVA) and treatment-related side effects. From 23 patients included in the study, 2 patients had anterior uveitis, 19 had intermediate uveitis and 2 had panuveitis. The probability of reactivation-free survival after MPS initiation was estimated as 65% at both 1 and 2 years. The probability of discontinuing systemic corticosteroids after 1 year of treatment was 39% and after 2 years 51%. The probability to taper corticosteroids to a daily dosage of ≤0.1 mg/kg after 1 and 2 years was 62% and 85%, respectively. BCVA improved or remained stable in 96% of eyes after 1 year of therapy. Treatment-related side effects were found in nine children (rate: 0.17/patient-year). No therapy discontinuation because of side effects was needed. Our data suggest that MPS is useful and well tolerated in children with chronic uveitis. MPS seems to be an effective drug for the treatment of chronic non-infectious uveitis of childhood and may be preferred as a first-line steroid-sparing agent in this form of uveitis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  10. Differential proteome analysis of human embryonic kidney cell line (HEK-293 following mycophenolic acid treatment

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    Rahman Hazir

    2011-09-01

    Full Text Available Abstract Background Mycophenolic acid (MPA is widely used as a post transplantation medicine to prevent acute organ rejection. In the present study we used proteomics approach to identify proteome alterations in human embryonic kidney cells (HEK-293 after treatment with therapeutic dose of MPA. Following 72 hours MPA treatment, total protein lysates were prepared, resolved by two dimensional gel electrophoresis and differentially expressed proteins were identified by QTOF-MS/MS analysis. Expressional regulations of selected proteins were further validated by real time PCR and Western blotting. Results The proliferation assay demonstrated that therapeutic MPA concentration causes a dose dependent inhibition of HEK-293 cell proliferation. A significant apoptosis was observed after MPA treatment, as revealed by caspase 3 activity. Proteome analysis showed a total of 12 protein spots exhibiting differential expression after incubation with MPA, of which 7 proteins (complement component 1 Q subcomponent-binding protein, electron transfer flavoprotein subunit beta, cytochrome b-c1 complex subunit, peroxiredoxin 1, thioredoxin domain-containing protein 12, myosin regulatory light chain 2, and profilin 1 showed significant increase in their expression. The expression of 5 proteins (protein SET, stathmin, 40S ribosomal protein S12, histone H2B type 1 A, and histone H2B type 1-C/E/F/G/I were down-regulated. MPA mainly altered the proteins associated with the cytoskeleton (26%, chromatin structure/dynamics (17% and energy production/conversion (17%. Both real time PCR and Western blotting confirmed the regulation of myosin regulatory light chain 2 and peroxiredoxin 1 by MPA treatment. Furthermore, HT-29 cells treated with MPA and total kidney cell lysate from MMF treated rats showed similar increased expression of myosin regulatory light chain 2. Conclusion The emerging use of MPA in diverse pathophysiological conditions demands in-depth studies to

  11. Mycophenolate pharmacokinetics and pharmacodynamics in belatacept treated renal allograft recipients – a pilot study

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    Stenstrøm Jean

    2009-07-01

    Full Text Available Abstract Background Mycophenolic acid (MPA is widely used as part of immunosuppressive regimens following allograft transplantation. The large pharmacokinetic (PK and pharmacodynamic (PD variability and narrow therapeutic range of MPA provide a potential for therapeutic drug monitoring. The objective of this pilot study was to investigate the MPA PK and PD relation in combination with belatacept (2nd generation CTLA4-Ig or cyclosporine (CsA. Methods Seven renal allograft recipients were randomized to either belatacept (n = 4 or cyclosporine (n = 3 based immunosuppression. Samples for MPA PK and PD evaluations were collected predose and at 1, 2 and 13 weeks posttransplant. Plasma concentrations of MPA were determined by HPLC-UV. Activity of inosine monophosphate dehydrogenase (IMPDH and the expressions of two IMPDH isoforms were measured in CD4+ cells by HPLC-UV and real-time reverse-transcription PCR, respectively. Subsets of T cells were characterized by flow cytometry. Results The MPA exposure tended to be higher among belatacept patients than in CsA patients at week 1 (P = 0.057. Further, MPA concentrations (AUC0–9 h and C0 increased with time in both groups and were higher at week 13 than at week 2 (P = 0.031, n = 6. In contrast to the postdose reductions of IMPDH activity observed early posttransplant, IMPDH activity within both treatment groups was elevated throughout the dosing interval at week 13. Transient postdose increments were also observed for IMPDH1 expression, starting at week 1. Higher MPA exposure was associated with larger elevations of IMPDH1 (r = 0.81, P = 0.023, n = 7 for MPA and IMPDH1 AUC0–9 h at week 1. The maximum IMPDH1 expression was 52 (13–177% higher at week 13 compared to week 1 (P = 0.031, n = 6. One patient showed lower MPA exposure with time and did neither display elevations of IMPDH activity nor IMPDH1 expression. No difference was observed in T cell subsets between treatment groups. Conclusion The

  12. [Clinical guideline for the treatment of lupus nephritis and single-centre results of mycofenolate mofetil among patients with lupus nephritis in the National Institute of Rheumatology and Physiotherapy, Budapest].

    Science.gov (United States)

    Szabó, Melinda Zsuzsanna; Kiss, Emese

    2016-08-01

    The authors present the latest guideline for the treatment of lupus nephritis and their own single-centre results with mycofenolate mofetil treated lupus nephritis. Lupus nephritis and mainly its proliferative form is a frequent and potentially life-threatening manifestation of systemic lupus erythematosus that can lead to end-stage renal disease. The treatment of lupus nephritis greatly improved in the last decades; mycofenolate mofetil has become an alternative of cyclophosphamide both in remission induction and as a maintenance regimen as well in the treatment of Class III and IV glomerulonephritis. The authors ordered mycofenolate mofetil for 25 patients with lupus nephritis so far. Histologically most of them had Class III (A/C) or IV (A) glomerulonephritis (30-30%), and only 16% of the patients had renal impairment at that time. Mycofenolate mofetil given after glucocorticoid and cyclophosphamide induction therapy reduced the daily proteinuria from 3.18 grs to 1.06 grs. Complete remission could be achieved in 24% and partial remission in 48% of the patients. The authors conclude that mycofenolate mofetil is effective in the therapy of lupus nephritis. Orv. Hetil., 2016, 157(35), 1385-1393.

  13. Determination of mycophenolic acid in mest products using mixed mode reversed phase-anion exchange clean-up and liquid chromatography-high-resolution mass spectrometry

    DEFF Research Database (Denmark)

    Sørensen, Louise Marie; Nielsen, Kristian Fog; Jacobsen, Thomas

    2008-01-01

    A method for determination of mycophenolic acid (MPA) in dry-cured ham, fermented sausage and liver pate is described. MPA was extracted from meat with bicarbonate-acetonitrile, further cleaned-up by mixed mode reversed phase-anion exchange and detected using a LC-MS system with electrospray...

  14. A comprehensive review of the published assays for the quantitation of the immunosuppressant drug mycophenolic acid and its glucuronidated metabolites in biological fluids

    DEFF Research Database (Denmark)

    Syed, Muzeeb; Srinivas, Nuggehally R

    2016-01-01

    Therapeutic use of mycophenolic acid (MPA) is steadily on the rise in combination with other immunosuppressant drugs in transplantation patients. The biotransformation of MPA resulted in the formation of glucuronide metabolites, MPAG and AcMPAG. There are a plethora of assays validated for the an...

  15. Comparative analysis the binding affinity of mycophenolic sodium and meprednisone with human serum albumin: Insight by NMR relaxation data and docking simulation.

    Science.gov (United States)

    Ma, Xiaoli; He, Jiawei; Yan, Jin; Wang, Qing; Li, Hui

    2016-03-25

    Mycophenolic sodium is an immunosuppressive agent that is always combined administration with corticosteroid in clinical practice. Considering the distribution and side-effect of the drug may change when co-administrated drug exist, this paper comparatively analyzed the binding ability of mycophenolic sodium and meprednisone toward human serum albumin by nuclear magnetic resonance relaxation data and docking simulation. The nuclear magnetic resonance approach was based on the analysis of proton selective and non-selective relaxation rate enhancement of the ligand in the absence and presence of macromolecules. The contribution of the bound ligand fraction to the observed relaxation rate in relation to protein concentration allowed the calculation of the affinity index. This approach allowed the comparison of the binding affinity of mycophenolic sodium and meprednisone. Molecular modeling was operated to simulate the binding model of ligand and albumin through Autodock 4.2.5. Competitive binding of mycophenolic sodium and meprednisone was further conducted through fluorescence spectroscopy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. A six-hour extrapolated sampling strategy for monitoring mycophenolic acid in renal transplant patients in the Indian subcontinent

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    Fleming D

    2006-01-01

    Full Text Available Background : Therapeutic drug monitoring for mycophenolic acid (MPA is increasingly being advocated. Thepresent therapeutic range relates to the 12-hour area under the serum concentration time profile (AUC.However, this is a cumbersome, tedious, cost restricting procedure. Is it possible to reduce this samplingperiod? Aim : To compare the AUC from a reduced sampling strategy with the full 12-hour profile for MPA. Settings and Design : Clinical Pharmacology Unit of a tertiary care hospital in South India. Retrospective, paireddata. Materials and Methods : Thirty-four 12-hour profiles from post-renal transplant patients on Cellcept ® wereevaluated. Profiles were grouped according to steroid and immunosuppressant co-medication and the timeafter transplant. MPA was estimated by high performance liquid chromatography with UV detection. From the12-hour profiles the AUC up to only six hours was calculated by the trapezoidal rule and a correction factorapplied. These two AUCs were then compared. Statistical Analysis : Linear regression, intra-class correlations (ICC and a two-tailed paired t-test were appliedto the data. Results : Comparing the 12-hour AUC with the paired 6-hour extrapolated AUC, the ICC and linear regression(r2 were very good for all three groups. No statistical difference was found by a two-tailed paired t-test. Nobias was seen with a Bland Altman plot or by calculation. Conclusion : For patients on Cellcept ® with prednisolone ± cyclosporine the 6-hour corrected is an accuratemeasure of the full 12-hour AUC.

  17. Differential Sensitivities of Fast- and Slow-Cycling Cancer Cells to Inosine Monophosphate Dehydrogenase 2 Inhibition by Mycophenolic Acid

    Science.gov (United States)

    Chen, Kan; Cao, Wanlu; Li, Juan; Sprengers, Dave; Hernanda, Pratika Y; Kong, Xiangdong; van der Laan, Luc JW; Man, Kwan; Kwekkeboom, Jaap; Metselaar, Herold J; Peppelenbosch, Maikel P; Pan, Qiuwei

    2015-01-01

    As uncontrolled cell proliferation requires nucleotide biosynthesis, inhibiting enzymes that mediate nucleotide biosynthesis constitutes a rational approach to the management of oncological diseases. In practice, however, results of this strategy are mixed and thus elucidation of the mechanisms by which cancer cells evade the effect of nucleotide biosynthesis restriction is urgently needed. Here we explored the notion that intrinsic differences in cancer cell cycle velocity are important in the resistance toward inhibition of inosine monophosphate dehydrogenase (IMPDH) by mycophenolic acid (MPA). In short-term experiments, MPA treatment of fast-growing cancer cells effectively elicited G0/G1 arrest and provoked apoptosis, thus inhibiting cell proliferation and colony formation. Forced expression of a mutated IMPDH2, lacking a binding site for MPA but retaining enzymatic activity, resulted in complete resistance of cancer cells to MPA. In nude mice subcutaneously engrafted with HeLa cells, MPA moderately delayed tumor formation by inhibiting cell proliferation and inducing apoptosis. Importantly, we developed a lentiviral vector–based Tet-on label-retaining system that enables to identify, isolate and functionally characterize slow-cycling or so-called label-retaining cells (LRCs) in vitro and in vivo. We surprisingly found the presence of LRCs in fast-growing tumors. LRCs were superior in colony formation, tumor initiation and resistance to MPA as compared with fast-cycling cells. Thus, the slow-cycling compartment of cancer seems predominantly responsible for resistance to MPA. PMID:26467706

  18. A new class of IMP dehydrogenase with a role in self-resistance of mycophenolic acid producing fungi

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    Mortensen Uffe H

    2011-09-01

    Full Text Available Abstract Background Many secondary metabolites produced by filamentous fungi have potent biological activities, to which the producer organism must be resistant. An example of pharmaceutical interest is mycophenolic acid (MPA, an immunosuppressant molecule produced by several Penicillium species. The target of MPA is inosine-5'-monophosphate dehydrogenase (IMPDH, which catalyses the rate limiting step in the synthesis of guanine nucleotides. The recent discovery of the MPA biosynthetic gene cluster from Penicillium brevicompactum revealed an extra copy of the IMPDH-encoding gene (mpaF embedded within the cluster. This finding suggests that the key component of MPA self resistance is likely based on the IMPDH encoded by mpaF. Results In accordance with our hypothesis, heterologous expression of mpaF dramatically increased MPA resistance in a model fungus, Aspergillus nidulans, which does not produce MPA. The growth of an A. nidulans strain expressing mpaF was only marginally affected by MPA at concentrations as high as 200 μg/ml. To further substantiate the role of mpaF in MPA resistance, we searched for mpaF orthologs in six MPA producer/non-producer strains from Penicillium subgenus Penicillium. All six strains were found to hold two copies of IMPDH. A cladistic analysis based on the corresponding cDNA sequences revealed a novel group constituting mpaF homologs. Interestingly, a conserved tyrosine residue in the original class of IMPDHs is replaced by a phenylalanine residue in the new IMPDH class. Conclusions We identified a novel variant of the IMPDH-encoding gene in six different strains from Penicillium subgenus Penicillium. The novel IMPDH variant from MPA producer P. brevicompactum was shown to confer a high degree of MPA resistance when expressed in a non-producer fungus. Our study provides a basis for understanding the molecular mechanism of MPA resistance and has relevance for biotechnological and pharmaceutical applications.

  19. Eficácia do regime terapêutico empregando a associação de pantoprazol, claritromicina e amoxicilina, durante uma semana, na erradicação do Helicobacter pylori em pacientes com úlcera péptica Efficacy of the dosing regimen of pantoprazole 40 mg, amoxicillin 1000 mg and clarithromycin 500 mg, twice daily for 7 days, in the eradication of Helicobacter pylori in patients with peptic ulcer

    Directory of Open Access Journals (Sweden)

    Luiz Gonzaga Vaz Coelho

    2004-03-01

    Full Text Available OBJETIVO: Estudo multicêntrico, aberto, delineado para determinar a eficácia da associação de pantoprazol, claritromicina e amoxicilina, na erradicação do Helicobacter pylori em pacientes portadores de úlcera péptica. MATERIAL E MÉTODOS: Setenta e um pacientes (36 mulheres, 35 homens, idade média 41,9 anos provenientes de três centros universitários brasileiros (Belo Horizonte e Porto Alegre com úlcera péptica confirmada à endoscopia e infecção por H. pylori comprovada por, no mínimo, dois testes diagnósticos. Os pacientes foram tratados com a associação de pantoprazol 40 mg, claritromicina 500 mg e amoxicilina 1,0 g, administrada duas vezes ao dia, durante 7 dias. RESULTADOS: Ao final do tratamento, os pacientes foram reexaminados para avaliação dos sintomas gastrointestinais, presença de eventos adversos e aderência ao tratamento. Nova endoscopia com biopsias e teste respiratório com 13C-uréia foram repetidos 60 dias após o término do tratamento para determinação das taxas de erradicação do microrganismo. Foram considerados H. pylori negativos os pacientes com, pelo menos, o teste respiratório com 13C-uréia e mais um teste (teste da urease ou histologia negativos. Ao final do estudo 60/69 (87%, 95% = 78,9-94,8 pacientes erradicaram o H. pylori na análise por protocolo e 60/71 (84,5%, 95% = 76-92,9 na análise por intenção de tratamento. Um paciente interrompeu o tratamento devido à diarréia. Doze pacientes (16,9% apresentaram sintomas adversos e considerados de leve intensidade. CONCLUSÃO: A associação de pantoprazol, amoxicilina e claritromicina por 7 dias constitui alternativa eficaz e bem tolerada para a erradicação do H. pylori em portadores de úlcera péptica no Brasil.AIM: This is an open label, multicenter trial to determine the efficacy of the association of pantoprazole, clarithromycin and amoxicillin to eradicate Helicobacter pylory in patients with peptic ulcer. MATERIAL AND METHODS

  20. A new and novel treatment of opioid dependence: nigella sativa 500 mg

    International Nuclear Information System (INIS)

    Sangi, S.; Ahmed, S.P.; Channa, M.A.

    2008-01-01

    Opioid dependence is one of the major social and psychiatric problem of society. Unfortunately there is no non opiate treatment available. For centuries man has used plants for their healing proprieties. These plants play a fundamental part in all treatment modalities, both ancient and modern. This study was conducted to find non opiate treatment for opiate withdrawal. Total 35 known addicts of opiates were included in the study. This study was based on DSM IV criteria for opioid dependence. This study demonstrates that non opioid treatment for opioid addiction decreases the withdrawal effects significantly. It further demonstrates that there are no changes in physiological parameters of subjects during treatment (BP, Pulse rate etc.). There is increased appetite but no significant weight gain in the subjects. Non opioid drug Nigella sativa is effective in long term treatment of opioid dependence. It not merely cures the opioid dependence but also cures the infections and weakness from which majority of addicts suffer. (author)

  1. The prevalence of side-effects: ciprofloxacin 500 mg single dose ...

    African Journals Online (AJOL)

    Potchefstroom experienced an outbreak of Neisseria meningitidis (N. meningitidis) during May-July 2003. An opportunity for obtaining valuable data arose when mass prophylactic treatment to approximately 28% of the Potchefstroom community was provided by the Department of Health, North-West Province. The aim of ...

  2. Evaluation of Multiple Linear Regression-Based Limited Sampling Strategies for Enteric-Coated Mycophenolate Sodium in Adult Kidney Transplant Recipients.

    Science.gov (United States)

    Brooks, Emily K; Tett, Susan E; Isbel, Nicole M; McWhinney, Brett; Staatz, Christine E

    2018-04-01

    Although multiple linear regression-based limited sampling strategies (LSSs) have been published for enteric-coated mycophenolate sodium, none have been evaluated for the prediction of subsequent mycophenolic acid (MPA) exposure. This study aimed to examine the predictive performance of the published LSS for the estimation of future MPA area under the concentration-time curve from 0 to 12 hours (AUC0-12) in renal transplant recipients. Total MPA plasma concentrations were measured in 20 adult renal transplant patients on 2 occasions a week apart. All subjects received concomitant tacrolimus and were approximately 1 month after transplant. Samples were taken at 0, 0.33, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours and 0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 9, and 12 hours after dose on the first and second sampling occasion, respectively. Predicted MPA AUC0-12 was calculated using 19 published LSSs and data from the first or second sampling occasion for each patient and compared with the second occasion full MPA AUC0-12 calculated using the linear trapezoidal rule. Bias (median percentage prediction error) and imprecision (median absolute prediction error) were determined. Median percentage prediction error and median absolute prediction error for the prediction of full MPA AUC0-12 were multiple linear regression-based LSS was not possible without concentrations up to at least 8 hours after the dose.

  3. Download this PDF file

    African Journals Online (AJOL)

    Proff.Adewunmi

    Western blot in 2004 at National Institute of Medical Research, Lagos (NIMR). ... However, HIV infection is still believed to be incurable and can only be ..... highly active antiretroviral therapy and mycophenolate mofetil, AIDS: 18 (11) 1607-8.

  4. Severe Interstitial Lung Disease and Manic Symptoms Secondary to Corticosteroids in a Patient with Systemic Lupus Erythematosus and Secondary Sjögren’s Syndrome

    Directory of Open Access Journals (Sweden)

    Sofia Silvério Serra

    2017-03-01

    We introduced monthly perfusion of cyclophosphamide for six months and later started mycophenolate mofetil 2 g/day, reducing prednisolone to 10 mg/day and maintaining hydroxychloroquine 400 mg/day, with control of disease activity.

  5. A possible simplification for the estimation of area under the curve (AUC₀₋₁₂) of enteric-coated mycophenolate sodium in renal transplant patients receiving tacrolimus.

    Science.gov (United States)

    Fleming, Denise H; Mathew, Binu S; Prasanna, Samuel; Annapandian, Vellaichamy M; John, George T

    2011-04-01

    Enteric-coated mycophenolate sodium (EC-MPS) is widely used in renal transplantation. With a delayed absorption profile, it has not been possible to develop limited sampling strategies to estimate area under the curve (mycophenolic acid [MPA] AUC₀₋₁₂), which have limited time points and are completed in 2 hours. We developed and validated simplified strategies to estimate MPA AUC₀₋₁₂ in an Indian renal transplant population prescribed EC-MPS together with prednisolone and tacrolimus. Intensive pharmacokinetic sampling (17 samples each) was performed in 18 patients to measure MPA AUC₀₋₁₂. The profiles at 1 month were used to develop the simplified strategies and those at 5.5 months used for validation. We followed two approaches. In one, the AUC was calculated using the trapezoidal rule with fewer time points followed by an extrapolation. In the second approach, by stepwise multiple regression analysis, models with different time points were identified and linear regression analysis performed. Using the trapezoidal rule, two equations were developed with six time points and sampling to 6 or 8 hours (8hrAUC[₀₋₁₂exp]) after the EC-MPS dose. On validation, the 8hrAUC(₀₋₁₂exp) compared with total measured AUC₀₋₁₂ had a coefficient of correlation (r²) of 0.872 with a bias and precision (95% confidence interval) of 0.54% (-6.07-7.15) and 9.73% (5.37-14.09), respectively. Second, limited sampling strategies were developed with four, five, six, seven, and eight time points and completion within 2 hours, 4 hours, 6 hours, and 8 hours after the EC-MPS dose. On validation, six, seven, and eight time point equations, all with sampling to 8 hours, had an acceptable r with the total measured MPA AUC₀₋₁₂ (0.817-0.927). In the six, seven, and eight time points, the bias (95% confidence interval) was 3.00% (-4.59 to 10.59), 0.29% (-5.4 to 5.97), and -0.72% (-5.34 to 3.89) and the precision (95% confidence interval) was 10

  6. A novel freeze-dried storage and preparation method for the determination of mycophenolic acid in plasma by high-performance liquid chromatography.

    Science.gov (United States)

    Wang, Lei; Qiang, Wei; Li, Ying; Cheng, Zeneng; Xie, Mengmeng

    2017-09-01

    Plasma samples were conventionally stored at freezing conditions until the time of detection. Such a technique, when carried out over an extended period, is energy consuming; in addition, preparation and transportation of stored samples is inconvenient. In this study, a freeze-dried storage and preparation method was proposed to determine the presence of mycophenolic acid (MPA) in plasma. Fresh plasma samples were freeze-dried using a device, and then stored at ambient temperature. After the stored samples were soaked with methanol spiked with the internal standard, high-performance liquid chromatography was conducted to detect MPA. The proposed method was demonstrated to be precise and accurate over the linear range of 0.5-50 μg mL -1 , with both intra- and inter-day precision being plasma concentration, time point of maximum plasma concentration and elimination half-life, among others, were consistent with the results in the published study. This proposed technique was proved to be simple, reproducible and energy saving. This approach could also simplify the storage and analysis of samples in clinical and scientific drug research. Copyright © 2017 John Wiley & Sons, Ltd.

  7. A comprehensive review of the published assays for the quantitation of the immunosuppressant drug mycophenolic acid and its glucuronidated metabolites in biological fluids.

    Science.gov (United States)

    Syed, Muzeeb; Srinivas, Nuggehally R

    2016-05-01

    Therapeutic use of mycophenolic acid (MPA) is steadily on the rise in combination with other immunosuppressant drugs in transplantation patients. The biotransformation of MPA resulted in the formation of glucuronide metabolites, MPAG and AcMPAG. There are a plethora of assays validated for the analysis of MPA alone or with MPAG/AcMPAG in various biological specimens including plasma/serum, urine, ultrafiltrate, saliva, PBMC, dried blood spots, tissue extract, tumor biopsies and vitreous humor. Based on the need for experimental work, a proper choice of the assay and internal standard may be made using the choices in the literature. While the chemical methods involving high-performance liquid chromatography (HPLC) or LC coupled with triple quadrupole mass spectrometry (LC-MS/MS) are popular, enzymatic assays, in spite of their higher bias, have been used for the routine drug monitoring of MPA. The objectives of the present review are: (a) to provide a focused systematic compilation of the HPLC or LC-MS/MS methods for MPA, MPAG and/or AcMPAG published in the last decade (2005 to current) to enable visual comparison of the methods; (b) to compare and contrast a few enzymatic assays with those of the chemical methods; and (c) to discuss relevant issues/limitations and perspectives on select assays under various subheadings. Copyright © 2016 John Wiley & Sons, Ltd.

  8. Three-Year Outcomes in Kidney Transplant Patients Randomized to Steroid-Free Immunosuppression or Steroid Withdrawal, with Enteric-Coated Mycophenolate Sodium and Cyclosporine: The Infinity Study

    Directory of Open Access Journals (Sweden)

    A. Thierry

    2014-01-01

    Full Text Available In a six-month, multicenter, open-label trial, de novo kidney transplant recipients at low immunological risk were randomized to steroid avoidance or steroid withdrawal with IL-2 receptor antibody (IL-2RA induction, enteric-coated mycophenolate sodium (EC-MPS: 2160 mg/day to week 6, 1440 mg/day thereafter, and cyclosporine. Results from a 30-month observational follow-up study are presented. Of 166 patients who completed the core study on treatment, 131 entered the follow-up study (70 steroid avoidance, 61 steroid withdrawal. The primary efficacy endpoint of treatment failure (clinical biopsy-proven acute rejection (BPAR graft loss, death, or loss to follow-up occurred in 21.4% (95% CI 11.8–31.0% of steroid avoidance patients and 16.4% (95% CI 7.1–25.7% of steroid withdrawal patients by month 36 (P=0.46. BPAR had occurred in 20.0% and 11.5%, respectively (P=0.19. The incidence of adverse events with a suspected relation to steroids during months 6–36 was 22.9% versus 37.1% (P=0.062. By month 36, 32.4% and 51.7% of patients in the steroid avoidance and steroid withdrawal groups, respectively, were receiving oral steroids. In conclusion, IL-2RA induction with early intensified EC-MPS dosing and CNI therapy in de novo kidney transplant patients at low immunological risk may achieve similar three-year efficacy regardless of whether oral steroids are withheld for at least three months.

  9. Determination of Mycophenolic acid in the vitreous humor using the HPLC-ESI-MS/MS method: application of intraocular pharmacokinetics study in rabbit eyes with ophthalmic implantable device.

    Science.gov (United States)

    Martins Duarte Byrro, Ricardo; de Oliveira Fulgêncio, Gustavo; Rocha Chellini, Paula; da Silva Cunha, Armando; Pianetti, Gerson Antônio

    2013-10-01

    Mycophenolic acid (MPA) is an immunosuppressive agent widely used in the treatment of solid organ transplant rejection. The success of MPA in the treatment of inflammatory intraocular diseases has been reported in recent literature. The treatment of inflammatory eye diseases in the posterior chamber is a challenge due to the anatomy of the eye, which presents certain barriers to drug access. Thus, the bioavailability of drugs in the eye is quite low, and successful drug delivery may well represent a key limiting factor to attaining a successful therapeutic strategy. Ophthalmic controlled drug delivery offers the potential to enhance the efficacy of treatment for pathological conditions. Thus, a novel delivery system based on a biodegradable polymeric device, which can be implanted inside the eye and deliver MPA directly to the target, is being developed. Specific analytical methods to determine the use of effective drugs within the eye are needed to characterize this device. A liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) method for the quantitation of MPA in the vitreous humor of rabbits was developed and validated. The vitreous was collected from rabbits, extracted by a protein precipitation extraction procedure and then separated on a C18 column with a mobile phase comprised of 0.15% aqueous acetic acid and methanol (60:40, v/v). The calibration curve was constructed within the range of 3-10,000 ng/mL for MPA. The mean R.S.D. values for the intra-run and inter-run precision were 5.15% and 4.35%. The mean accuracy value was 100.16%. The validated method was successfully applied to determine the MPA concentration in the vitreous humor of rabbits treated with an ocular implantable device. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Induction of immunological tolerance in the pig-to-baboon xenotransplantation model : studies aimed at achieving mixed hematopoietic chimerism and preventing associated thrombotic complications

    NARCIS (Netherlands)

    I.P.J. Alwayn (Ian)

    2001-01-01

    textabstractThe outcome of clinical organ transplantation has dramatically improved since the introduction of cyclosporine (CyA) in 1979 and of other, more recently introduced, immunosuppressive agents such as azathioprine, mycophenolate mofetil, tacrolimus and sirolimus. Furthermore, due to more

  11. B cells and immunoglobulin in ABO-incompatible renal transplant patients receiving rituximab and double filtration plasmapheresis

    Directory of Open Access Journals (Sweden)

    Meng-Kun Tsai

    2015-04-01

    Conclusion: With the aid of tacrolimus and mycophenolate mofetil, rituximab resulted in sustained suppression of B cell count and total IgG and IgM. Among the IgG subclasses, IgG3 was less sensitive to rituximab.

  12. Outcomes of immunosuppressive therapy in chronic hypersensitivity pneumonitis

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    Ayodeji Adegunsoye

    2017-08-01

    Full Text Available In chronic hypersensitivity pneumonitis (CHP, lack of improvement or declining lung function may prompt use of immunosuppressive therapy. We hypothesised that use of azathioprine or mycophenolate mofetil with prednisone reduces adverse events and lung function decline, and improves transplant-free survival. Patients with CHP were identified. Demographic features, pulmonary function tests, incidence of treatment-emergent adverse events (TEAEs and transplant-free survival were characterised, compared and analysed between patients stratified by immunosuppressive therapy. A multicentre comparison was performed across four independent tertiary medical centres. Among 131 CHP patients at the University of Chicago medical centre (Chicago, IL, USA, 93 (71% received immunosuppressive therapy, and had worse baseline forced vital capacity (FVC and diffusing capacity, and increased mortality compared with those who did not. Compared to patients treated with prednisone alone, TEAEs were 54% less frequent with azathioprine therapy (p=0.04 and 66% less frequent with mycophenolate mofetil (p=0.002. FVC decline and survival were similar between treatment groups. Analyses of datasets from four external tertiary medical centres confirmed these findings. CHP patients who did not receive immunosuppressive therapy had better survival than those who did. Use of mycophenolate mofetil or azathioprine was associated with a decreased incidence of TEAEs, and no difference in lung function decline or survival when compared with prednisone alone. Early transition to mycophenolate mofetil or azathioprine may be an appropriate therapeutic approach in CHP, but more studies are needed.

  13. Pro: Cyclophosphamide in lupus nephritis

    NARCIS (Netherlands)

    Kallenberg, Cees G. M.

    Based on efficacy and toxicity considerations, both low-dose pulse cyclophosphamide as part of the Euro-Lupus Nephritis protocol and mycophenolate mofetil (MMF) with corticosteroids may be considered for induction of remission in patients with proliferative lupus nephritis. The long-term follow-up

  14. Severe neuropsychiatric systemic lupus erythematosus successfully treated with rituximab: an alternative to standard of care

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    Chessa E

    2017-09-01

    Full Text Available Elisabetta Chessa, Matteo Piga, Alberto Floris, Alessandro Mathieu, Alberto Cauli Rheumatology Unit, University Clinic AOU of Cagliari, Cagliari, Italy Abstract: Demyelinating syndrome secondary to systemic lupus erythematosus (DS-SLE is a rare encephalomyelitis burden with a high risk of disability and death. We report on a 49-year-old Caucasian woman with systemic lupus erythematosus (SLE complicated by severe cognitive dysfunction, brainstem disease, cranial nerve palsies, weakness and numbness in limbs and multiple discrete magnetic resonance imaging (MRI areas of damage within the white matter of semioval centers, temporal lobe, external capsule, claustrum, subinsular regions and midbrain. She also had multiple mononeuritis diagnosed through sensory and motor nerve conduction study. She was diagnosed with severe DS-SLE prominently involving the brain and was treated with 500 mg methylprednisolone (PRE pulses for 3 consecutive days, followed by one single pulse of 500 mg cyclophosphamide, and 1 g rituximab, which was then repeated 14 days later. PRE 25 mg/day, rapidly tapered to 7.5 mg/day in 6 months, and mycophenolate mofetil 1 g/day were prescribed as maintenance therapy. She had progressive and sustained improvement in neurological symptoms with almost complete resolution of brain MRI lesions after 1 year. B-cell depleting therapy could be considered as a possible alternative to standard of care in the management of severe inflammatory neuropsychiatric SLE but it should be associated with a conventional immunosuppressant as maintenance treatment to reduce the risk of flare and reduce corticosteroids dose. Keywords: systemic lupus erythematosus, neuropsychiatric lupus, rituximab, demyelinating syndrome, brain MRI

  15. [Analgesic effect and clinical tolerability of the combination of paracetamol 500 mg and caffeine 50 mg versus paracetamol 400 mg and dextropropoxyphene 30 mg in back pain].

    Science.gov (United States)

    Kuntz, D; Brossel, R

    1996-09-07

    A double-blind randomized multicentric study was performed to test the hypothesis that the analgesic effect of paracetamol-cafeine is equivalent to that of paracetamol-dextropropoxyphen in patients suffering from pain due to osteoarthritis of the spine. Rhumatologists included 124 patients who were randomized into two groups of 62 each. Pain was measured daily during the seven-day treatment Huskisson's Analog Visual Scales; 112 were per protocol and evaluable. The two treatment groups were statistically similar for demographics, vital signs, medical and treatment history. A majority of them had pain located at the lumbar spine only; the other patients had either pain at the cervical or dorsal spine or at several sites. At the end of the week there was a major reduction in pain level: 51.2% in patients given paracetamol-cafeine and 47.0% in those given paracetamol-dextropropoxyphen. The main criteria of efficacy--the percentage of success (decrease of pain > 50%)--was similar in the two groups as well in the intention-to-treat population (p = 0.01) as the per protocol population (p = 0.028). Kinetics of pain decrease during the first day of treatment were assessed with an hourly evaluation during the six first hours and at the 12th hour. There was no difference between the two groups. There was no serious adverse event and the frequency and intensity of the adverse events were similar in the two groups. The potentializing action of cafeine on paracetamol-induced pain relief enables a degree of pain relief equivalent to that of a combination using an analgesic with a peripheral action, paracetamol, and another with a central action, dextropoxyphen. The fact that the paracetamol-cafeine combination does not have a central action avoids secondary effects induced by central analgesics (drowsiness, constipation) in patients with osteoarthritis back pain.

  16. COMPARAÇÃO ENTRE PREÇOS DE MEDICAMENTOS GENÉRICO, SIMILAR E REFERÊNCIA CONTENDO CIPROFLOXACINO 500 mg

    Directory of Open Access Journals (Sweden)

    Caroline Aparecida Lima

    2016-10-01

    Full Text Available Os Antimicrobianos são definidos como compostos naturais, sintéticos ou semi-sintéticos, cuja finalidade é prevenir ou tratar de doenças infecciosas causadas por micro-organismos patogênicos. Ele é comercializado sob prescrição médica e possui um medicamento de referência. O medicamento de referência é um produto inovador no mercado, que possui sua própria marca comercial. Ele tem qualidade, eficácia e segurança comprovados cientificamente através de testes que são registrados junto ao órgão federal ANVISA. .O objetivo do estudo é demonstrar a diferença de preços existente entre os medicamentos analisados. O valor dos medicamentos foi levantado através de pesquisa em drogarias, o que nos mostrou uma grande diferença de preço entre os medicamentos e quando comparado com o estudo que avaliou o princípio ativo, o medicamento com melhor custo benefício, são os similares

  17. Disseminated mycobacteria chelonae infection in a kidney-pancreas transplant recipient: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Shafi Malik

    2016-01-01

    Full Text Available A 40-year-old male with a long-standing history of type 1 diabetes with end-stage renal failure underwent combined kidney-pancreas (KP transplant from a standard criteria donor. Post-operative course was uncomplicated with good primary function of both transplant grafts. Induction was with thymoglobulin and maintenance immunosuppression was with tacrolimus, mycophenolate mofetil and prednisolone. Nine weeks post-transplant, the patient developed dysfunction of both grafts. Panel reactive antibody testing revealed that the patient had developed a de novo donor-specific antibody and considering an antibody-mediated rejection the patient was treated with intravenous pulse methyl prednisone 500 mg ×3 doses, IV immunoglobulin 2 mg/kg in two divided doses, and ATG 7 mg/kg (total dose of 700 mg. In addition, his baseline immunosuppression was increased. Cr decreased to baseline levels, and blood sugars were in the range of 7-8 mmol/L, serum amylase normalized to 63 U/L, and the patient was discharged home. Nine days post-discharge, the patient presented to the hospital with a five-day history of fever, pain, and swelling in the left knee along with subcutaneous, erythematous, tender, nodular lesions in both legs and both arms. Skin biopsy showed Ziehl-Neelsen stain positive rods and biopsy culture and blood culture grew Mycobacteria chelonae. Antimicrobials were switched to azithromycin 500 mg OD, moxifloxacin 400 mg OD, and linezolid 600 mg BID and baseline immunosuppression was reduced to tacrolimus trough target 8-10 ng/mL and MMF to 250 mg BID. The patient gradually improved and was discharged after 28 days in the hospital. Six weeks following the diagnosis of nontuberculous mycobacteria infection, the patient′s pancreas graft failed, presumably due to reduction in immuno-suppression and he is now back on insulin treatment. His renal graft continued to function well. Although rapidly growing mycobacterial infections are rare among transplant

  18. Toxic Epidermal Necrolysis-Like Lesions and Systemic Lupus Erythematosus Possibly Triggered by Sulfasalazine

    DEFF Research Database (Denmark)

    Krabbe, Simon; Gül, Cigdem; Andersen, Bjarne

    2016-01-01

    elevated ferritin, and muscle wasting. A diagnosis of systemic lupus erythematosus was made, and mycophenolate mofetil and systemic glucocorticoids brought this severe disease under control. Toxic epidermal necrolysis-like lesions and hemophagocytic syndrome have been reported as manifestations of systemic...... lupus erythematosus. This patient possibly had spondyloarthritis or an undifferentiated connective tissue disease at presentation, and we suggest, based on the timing of events, that sulfasalazine may have acted as a trigger of the severe disease manifestations....

  19. A Bayesian Analysis of a Randomized Clinical Trial Comparing Antimetabolite Therapies for Non-Infectious Uveitis.

    Science.gov (United States)

    Browne, Erica N; Rathinam, Sivakumar R; Kanakath, Anuradha; Thundikandy, Radhika; Babu, Manohar; Lietman, Thomas M; Acharya, Nisha R

    2017-02-01

    To conduct a Bayesian analysis of a randomized clinical trial (RCT) for non-infectious uveitis using expert opinion as a subjective prior belief. A RCT was conducted to determine which antimetabolite, methotrexate or mycophenolate mofetil, is more effective as an initial corticosteroid-sparing agent for the treatment of intermediate, posterior, and pan-uveitis. Before the release of trial results, expert opinion on the relative effectiveness of these two medications was collected via online survey. Members of the American Uveitis Society executive committee were invited to provide an estimate for the relative decrease in efficacy with a 95% credible interval (CrI). A prior probability distribution was created from experts' estimates. A Bayesian analysis was performed using the constructed expert prior probability distribution and the trial's primary outcome. A total of 11 of the 12 invited uveitis specialists provided estimates. Eight of 11 experts (73%) believed mycophenolate mofetil is more effective. The group prior belief was that the odds of treatment success for patients taking mycophenolate mofetil were 1.4-fold the odds of those taking methotrexate (95% CrI 0.03-45.0). The odds of treatment success with mycophenolate mofetil compared to methotrexate was 0.4 from the RCT (95% confidence interval 0.1-1.2) and 0.7 (95% CrI 0.2-1.7) from the Bayesian analysis. A Bayesian analysis combining expert belief with the trial's result did not indicate preference for one drug. However, the wide credible interval leaves open the possibility of a substantial treatment effect. This suggests clinical equipoise necessary to allow a larger, more definitive RCT.

  20. Dermatomyositis Sine Myositis with Membranoproliferative Glomerulonephritis

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    Mohammad Bagher Owlia

    2012-01-01

    Full Text Available Dermatomyositis (DM is an autoimmune disease that is characterized by involvement of proximal musculature and skin. We report a 52-year-old woman with a 6-year history of dermatomyositis sine myositis, who developed lower extremity edema and proteinuria. Pathological examination of renal biopsy showed membranoproliferative glomerulonephritis. She received steroid, cyclophosphamide, and mycophenolate mofetil. Over the 9 to 10 months after the beginning of treatment, the proteinuria was improved.

  1. Cytomegalovirus Disease in Renal Transplant Recipients: A Single-Center Experience

    OpenAIRE

    Bhadauria, Dharmendra; Sharma, R. K.; Kaul, A.; Prasad, Narayan; Gupta, Amit; Gupta, Anurag; Srivastava, Aneesh

    2012-01-01

    Cytomegalovirus (CMV) is the most common viral infection following kidney transplant, has been recognized as a major factor for graft loss and increased incidence of acute rejection. Different studies have reported a variable incidence of CMV disease with the use of Mycophenolate mofetil (MMF). We retrospectively analyzed our renal transplant recipients to review the results of CMV disease and to compare CMV disease in patient on Azathioprine and MMF for this purpose we retrospectively review...

  2. Current and emerging treatments for the management of myasthenia gravis

    Science.gov (United States)

    Sathasivam, Sivakumar

    2011-01-01

    Myasthenia gravis is an autoimmune neuromuscular disorder. There are several treatment options, including symptomatic treatment (acetylcholinesterase inhibitors), short-term immunosuppression (corticosteroids), long-term immunosuppression (azathioprine, cyclosporine, cyclophosphamide, methotrexate, mycophenolate mofetil, rituximab, tacrolimus), rapid acting short-term immunomodulation (intravenous immunoglobulin, plasma exchange), and long-term immunomodulation (thymectomy). This review explores in detail these different treatment options. Potential future treatments are also discussed. PMID:21845054

  3. Treatment of patients with severe autoimmune hepatitis

    DEFF Research Database (Denmark)

    Larsen, Finn Stolze

    2008-01-01

    Autoimmune hepatitis (AIH) is a progressive inflammatory diseases of unknown origin that is characterised by a necro-inflammatory and fibrotic process and may result in liver failure or uncompensated liver cirrhosis. Normally AIH is responsive to immunosuppressive therapy, and treatment aims...... and tacrolimus) might salvage patients from transplantation. Mycophenolate mofetil may also improve liver tests and reduce the requirement for corticosteroids. Besides, sirolimus is effective for treatment of de novo autoimmune hepatitis that sometimes develops after liver transplantation. Initial experience...

  4. Desensitization to Mycofenolate Mofetil: a novel 12 step protocol.

    Science.gov (United States)

    Smith, M; Gonzalez-Estrada, A; Fernandez, J; Subramanian, A

    2016-07-01

    The use of MMF has become standard practice in many solid organ transplant recipients due its efficacy and favorable risk profile compared to other immunosuppressants. There has been a single case report of successful MMF desensitization. However, this protocol did not follow current Drug practice parameters. We report a successful desensitization to MMF in a double heart-kidney transplant recipient.

  5. Pigmented villonodular synovitis of the hip in systemic lupus erythematosus: a case report

    Directory of Open Access Journals (Sweden)

    Anders Hans-Joachim

    2011-09-01

    Full Text Available Abstract Introduction Pigmented villonodular synovitis is a rare disease of unknown etiology mostly affecting the knee and foot. Until now an association with autoimmune diseases has not been reported. Case presentation The diagnosis of systemic lupus erythematosus was made in a 15-year-old Caucasian girl based on otherwise unexplained fatigue, arthralgia, tenosynovitis, leukopenia, low platelets and the presence of antinuclear and deoxyribonucleic antibodies. At the age of 20 a renal biopsy revealed lupus nephritis class IV and she went into complete remission with mycophenolate mofetil and steroids. She was kept on mycophenolate mofetil for maintenance therapy. At the age of 24 she experienced a flare-up of lupus nephritis with nephrotic syndrome and new onset of pain in her right hip. Magnetic resonance imaging, arthroscopy and subtotal synovectomy identified pigmented villonodular synovitis as the underlying diagnosis. Although her systemic lupus erythematosus went into remission with another course of steroids and higher doses of mycophenolate mofetil, the pigmented villonodular synovitis persisted and she had to undergo open synovectomy to control her symptoms. Conclusion Systemic lupus erythematosus is associated with many different musculoskeletal manifestations including synovitis and arthritis. Pigmented villonodular synovitis has not previously been reported in association with systemic lupus erythematosus, but as its etiology is still unknown, the present case raises the question about a causal relationship between systemic lupus erythematosus and pigmented villonodular synovitis.

  6. Elicitation of expert prior opinion: application to the MYPAN trial in childhood polyarteritis nodosa.

    Directory of Open Access Journals (Sweden)

    Lisa V Hampson

    Full Text Available Definitive sample sizes for clinical trials in rare diseases are usually infeasible. Bayesian methodology can be used to maximise what is learnt from clinical trials in these circumstances. We elicited expert prior opinion for a future Bayesian randomised controlled trial for a rare inflammatory paediatric disease, polyarteritis nodosa (MYPAN, Mycophenolate mofetil for polyarteritis nodosa.A Bayesian prior elicitation meeting was convened. Opinion was sought on the probability that a patient in the MYPAN trial treated with cyclophosphamide would achieve disease remission within 6-months, and on the relative efficacies of mycophenolate mofetil and cyclophosphamide. Expert opinion was combined with previously unseen data from a recently completed randomised controlled trial in ANCA associated vasculitis.A pan-European group of fifteen experts participated in the elicitation meeting. Consensus expert prior opinion was that the most likely rates of disease remission within 6 months on cyclophosphamide or mycophenolate mofetil were 74% and 71%, respectively. This prior opinion will now be taken forward and will be modified to formulate a Bayesian posterior opinion once the MYPAN trial data from 40 patients randomised 1:1 to either CYC or MMF become available.We suggest that the methodological template we propose could be applied to trial design for other rare diseases.

  7. Maintenance immunosuppression with intermittent intravenous IL-2 receptor antibody therapy in renal transplant recipients.

    Science.gov (United States)

    Gabardi, Steven; Catella, Jennifer; Martin, Spencer T; Perrone, Ronald; Chandraker, Anil; Magee, Colm C; McDevitt-Potter, Lisa M

    2011-09-01

    To report what we believe to be the first 2 cases of long-term (>24 months) intermittent intravenous interleukin-2 receptor antibody (IL-2RA) therapy for maintenance immunosuppression following renal transplantation. The first patient is a 52-year-old female with a history of intolerance to calcineurin inhibitors (CNIs) and sirolimus. Following her second transplant, the patient received mycophenolate mofetil 100 mg twice daily, a tapering corticosteroid regimen (initial dose of methylprednisolone 500 mg tapered over 1 week to prednisone 30 mg/day), and biweekly intravenous daclizumab 1-1.2 mg/kg/dose; 33 months after transplant the IL-2RA was changed to intravenous basiliximab 40 mg once a month. At 40 months after transplant, the patient continued to have stable renal function (estimated glomerular filtration rate 48 mL/min/1.73 m²) with excellent tolerability. The second patient is a 59-year-old female also intolerant to CNIs and sirolimus who required intermittent maintenance therapy with intravenous basiliximab 20 mg/dose. Despite an initial rejection episode, the patient tolerated more than 2 years of basiliximab therapy with good renal function (estimated glomerular filtration rate 103 months after transplant 69 mL/min/1.73 m²) and no adverse events. The IL-2RAs basiliximab and daclizumab possess several characteristics of ideal maintenance immunosuppressive agents (ie, nondepleting, long half-lives, limited adverse events). Based on a MEDLINE search (through December 31, 2010) using the search terms basiliximab, daclizumab, organ transplant, immunosuppression, and/or maintenance immunosuppression, and an advanced search in the published abstracts from the American Transplant Congress and World Transplant Congress (2000-2010), it appears that IL-2RAs have been used successfully as short-term therapy in both renal and extrarenal transplant recipients to allow for renal recovery following CNI-induced nephrotoxicity. In heart transplant recipients, the IL-2

  8. Treatment Algorithms in Systemic Lupus Erythematosus.

    Science.gov (United States)

    Muangchan, Chayawee; van Vollenhoven, Ronald F; Bernatsky, Sasha R; Smith, C Douglas; Hudson, Marie; Inanç, Murat; Rothfield, Naomi F; Nash, Peter T; Furie, Richard A; Senécal, Jean-Luc; Chandran, Vinod; Burgos-Vargas, Ruben; Ramsey-Goldman, Rosalind; Pope, Janet E

    2015-09-01

    To establish agreement on systemic lupus erythematosus (SLE) treatment. SLE experts (n = 69) were e-mailed scenarios and indicated preferred treatments. Algorithms were constructed and agreement determined (≥50% respondents indicating ≥70% agreement). Initially, 54% (n = 37) responded suggesting treatment for scenarios; 13 experts rated agreement with scenarios. Fourteen of 16 scenarios had agreement as follows: discoid lupus: first-line therapy was topical agents and hydroxychloroquine and/or glucocorticoids then azathioprine and subsequently mycophenolate (mofetil); uncomplicated cutaneous vasculitis: initial treatment was glucocorticoids ± hydroxychloroquine ± methotrexate, followed by azathioprine or mycophenolate and then cyclophosphamide; arthritis: initial therapy was hydroxychloroquine and/or glucocorticoids, then methotrexate and subsequently rituximab; pericarditis: first-line therapy was nonsteroidal antiinflammatory drugs, then glucocorticoids with/without hydroxychloroquine, then azathioprine, mycophenolate, or methotrexate and finally belimumab or rituximab, and/or a pericardial window; interstitial lung disease/alveolitis: induction was glucocorticoids and mycophenolate or cyclophosphamide, then rituximab or intravenous gamma globulin (IVIG), and maintenance followed with azathioprine or mycophenolate; pulmonary hypertension: glucocorticoids and mycophenolate or cyclophosphamide and an endothelin receptor antagonist were initial therapies, subsequent treatments were phosphodiesterase-5 inhibitors and then prostanoids and rituximab; antiphospholipid antibody syndrome: standard anticoagulation with/without hydroxychloroquine, then a thrombin inhibitor for venous thrombosis, versus adding aspirin or platelet inhibition drugs for arterial events; mononeuritis multiplex and central nervous system vasculitis: first-line therapy was glucocorticoids and cyclophosphamide followed by maintenance with azathioprine or mycophenolate, and

  9. Outcomes of Vogt-Koyanagi-Harada disease: a subanalysis from a randomized clinical trial of antimetabolite therapies

    Science.gov (United States)

    Shen, Elizabeth; Rathinam, Sivakumar R.; Babu, Manohar; Kanakath, Anuradha; Thundikandy, Radhika; Lee, Salena M.; Browne, Erica N.; Porco, Travis C.; Acharya, Nisha R.

    2016-01-01

    Purpose To report outcomes of Vogt-Koyanagi-Harada (VKH) disease from a clinical trial of antimetabolite therapies. Design Subanalysis from an observer-masked randomized clinical trial for non-infectious intermediate, posterior, and pan- uveitis. Methods Setting clinical practice at Aravind Eye Hospitals, India Patient Population Forty-three of 80 patients enrolled (54%) diagnosed with VKH. Intervention Patients were randomized to either 25mg oral methotrexate weekly or 1g mycophenolate mofetil twice daily, with a corticosteroid taper. Main outcome measures Primary outcome was corticosteroid-sparing control of inflammation at 5 and 6 months. Secondary outcomes included visual acuity, central subfield thickness, and adverse events. Patients were categorized as acute (diagnosis ≤3 months prior to enrollment) or chronic (diagnosis >3 months prior to enrollment). Results Twenty-seven patients were randomized to methotrexate and 16 to mycophenolate mofetil; 30 had acute VKH. The odds of achieving corticosteroid-sparing control of inflammation with methotrexate were 2.5 times (95% CI: 0.6, 9.8; P=0.20) the odds with mycophenolate mofetil, a difference which was not statistically significant. The average improvement in visual acuity was 12.5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters. On average, visual acuity for patients with acute VKH improved by 14 more ETDRS letters than those with chronic VKH (P<0.001), but there was no difference in corticosteroid-sparing control of inflammation (P=0.99). All 26 eyes with a serous retinal detachment at baseline resolved, and 88% achieved corticosteroid-sparing control of inflammation. Conclusions The majority of patients treated with antimetabolites and corticosteroids were able to achieve corticosteroid-sparing control of inflammation by 6 months. Although patients with acute VKH gained more visual improvement than those with chronic VKH, this did not correspond with a higher rate of controlled inflammation. PMID

  10. Acridone-based inhibitors of inosine 5'-monophosphate dehydrogenase: discovery and SAR leading to the identification of N-(2-(6-(4-ethylpiperazin-1-yl)pyridin-3-yl)propan-2-yl)-2- fluoro-9-oxo-9,10-dihydroacridine-3-carboxamide (BMS-566419).

    Science.gov (United States)

    Watterson, Scott H; Chen, Ping; Zhao, Yufen; Gu, Henry H; Dhar, T G Murali; Xiao, Zili; Ballentine, Shelley K; Shen, Zhongqi; Fleener, Catherine A; Rouleau, Katherine A; Obermeier, Mary; Yang, Zheng; McIntyre, Kim W; Shuster, David J; Witmer, Mark; Dambach, Donna; Chao, Sam; Mathur, Arvind; Chen, Bang-Chi; Barrish, Joel C; Robl, Jeffrey A; Townsend, Robert; Iwanowicz, Edwin J

    2007-07-26

    Inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the de novo synthesis of guanosine nucleotides, catalyzes the irreversible nicotinamide-adenine dinucleotide dependent oxidation of inosine-5'-monophosphate to xanthosine-5'-monophosphate. Mycophenolate Mofetil (MMF), a prodrug of mycophenolic acid, has clinical utility for the treatment of transplant rejection based on its inhibition of IMPDH. The overall clinical benefit of MMF is limited by what is generally believed to be compound-based, dose-limiting gastrointestinal (GI) toxicity that is related to its specific pharmacokinetic characteristics. Thus, development of an IMPDH inhibitor with a novel structure and a different pharmacokinetic profile may reduce the likelihood of GI toxicity and allow for increased efficacy. This article will detail the discovery and SAR leading to a novel and potent acridone-based IMPDH inhibitor 4m and its efficacy and GI tolerability when administered orally in a rat adjuvant arthritis model.

  11. Vasculitis and Pregnancy.

    Science.gov (United States)

    Machen, Leah; Clowse, Megan E B

    2017-05-01

    Vasculitis is more often a disease of women beyond their reproductive years, leaving the challenges of pregnancy management difficult to study. Pregnancy complications, including pregnancy loss and preterm birth, are higher among women with all forms of vasculitis. It seems that controlling the disease before pregnancy may improve the chances of pregnancy success. Many medications used for vasculitis are considered low risk in pregnancy, including prednisone, colchicine, azathioprine, and tumor necrosis factor inhibitors. Cyclophosphamide, methotrexate, and mycophenolate mofetil should be avoided in pregnancy. Controlling disease with low-risk medications may allow women with vasculitis to have the pregnancies they desire. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Central Diabetes Insipidus in Refractory Antineutrophil Cytoplasmic Antibody-associated Vasculitis.

    Science.gov (United States)

    Ohashi, Keiji; Morishita, Michiko; Watanabe, Haruki; Sada, Ken-Ei; Katsuyama, Takayuki; Miyawaki, Yoshia; Katsuyama, Eri; Narazaki, Mariko; Tatebe, Noriko; Watanabe, Katsue; Kawabata, Tomoko; Wada, Jun

    2017-11-01

    We herein describe two cases of refractory antineutrophil cytoplasmic antibody-associated vasculitis (AAV) complicated with diabetes insipidus (DI) possibly related to hypertrophic pachymeningitis (HP). One patient had microscopic polyangiitis and HP, which were refractory to cyclophosphamide, azathioprine, rituximab, mycophenolate mofetil (MMF), and mizoribine. Remission was finally achieved with the use of etanercept, but DI occurred 5 years later. The other patient had granulomatosis with polyangiitis, which that was refractory to cyclophosphamide, methotrexate, MMF, and rituximab. DI subsequently developed, but was successfully treated with etanercept. Dura mater hypertrophy was macroscopically observed in the latter case.

  13. Therapeutic Drug Monitoring in Rheumatic Diseases

    Directory of Open Access Journals (Sweden)

    NG Hoi-Yan Alexandra

    2016-12-01

    Full Text Available The ultimate goal of treating rheumatic disease is to achieve rapid suppression of inflammation, while at the same time minimizing the toxicities from rheumatic drugs. Different patients have different individual pharmacokinetics that can affect the drug level. Moreover, different factors, such as renal function, age or even different underlying diseases, can affect the drug level. Therefore, giving the same dosage of drugs to different patients may result in different drug levels. This article will review the usefulness of therapeutic drug monitoring in maximizing drug efficacy, while reducing the risk of toxicities in Hydroxychloroquine, Mycophenolate Mofetil, Tacrolimus and Tumor Necrosis Factor inhibitors (TNF Inhibitors.

  14. Treatment of refractory chronic urticaria

    Directory of Open Access Journals (Sweden)

    Aayushi Mehta

    2015-01-01

    Full Text Available Chronic spontaneous urticaria is a distressing disease encountered frequently in clinical practice. The current mainstay of therapy is the use of second-generation, non-sedating antihistamines. However, in patients who do not respond satisfactorily to these agents, a variety of other drugs are used. This article examines the available literature for frequently used agents including systemic corticosteroids, leukotriene receptor antagonists, dapsone, sulfasalazine, hydroxychloroquine, H2 antagonists, methotrexate, cyclosporine A, omalizumab, autologous serum therapy, and mycophenolate mofetil, with an additional focus on publications in Indian literature.

  15. Treatment of neuro-ophthalmic sarcoidosis.

    Science.gov (United States)

    Frohman, Larry P

    2015-03-01

    Because of the rarity of neuro-ophthalmic sarcoidosis, there are no therapeutic guidelines based on evidence-based medicine for this disorder. Review of literature combined with personal experience. Corticosteroids are the preferred initial therapy for neuro-ophthalmic sarcoidosis. If patients cannot tolerate the requisite dose of corticosteroid needed to control their disease, or if corticosteroids fail to adequately control the disease process, the choices of a second agent are based on the consideration of rapidity of clinical response and the safety profile. Although methotrexate and mycophenolate mofetil are the medications that are often selected after corticosteroid failure, more rapidly acting agents that have been used are infliximab and intravenous cyclophosphamide.

  16. Generalized morphea/eosinophilic fasciitis overlap after epoxy exposure

    Directory of Open Access Journals (Sweden)

    Warren H. Chan, MS

    2018-03-01

    Full Text Available Generalized morphea is associated with epoxy resin vapors and is characterized by the development of lesions shortly after exposure. Morphea presenting along with eosinophilic fasciitis (EF, or morphea/EF overlap, is rare and an indicator of poor prognosis and resistance to treatment. Here we present a case of generalized morphea/EF overlap linked to epoxy exposure. Our patient received multiple therapies—ultraviolet A1 phototherapy, prednisone, methotrexate, azathioprine, mycophenolate mofetil, cyclophosphamide, cyclosporine, and rituximab—none of which led to a significant response. The refractory nature of this disease warrants vigilance in its association with epoxy exposure.

  17. Enkeltcenteropgørelse af nyretransplanterede patienters nyrefunktion og immunsuppressive behandling

    DEFF Research Database (Denmark)

    Frederiksen, Anne Mette; Hansen, Jesper Melchior; Ewers, Bettina

    2008-01-01

    (131 males, 110 females) was equal. The average patient age was 52 years (SD 12), the average glomerular filtration rate 43 ml/min/1.73 m2 (range 6-114 ml/min/1.73 m2), and the average graft age was 8.3 years (range 0-28 years). Hyperparathyroidism was highly prevalent (64%). The majority of patients...... (74%) were treated with triple-drug immunosuppression, in most cases (46%) with the combination prednisolone-ciclosporine-azathioprine. During recent years, azathioprine has been increasingly replaced by mycophenolate mofetil. CONCLUSIONS: The majority of kidney-transplanted patients...

  18. Long-term experience of steroid-free pediatric renal transplantation

    DEFF Research Database (Denmark)

    Wittenhagen, Per; Thiesson, Helle C; Baudier, François

    2014-01-01

    Increased focus on the potential negative side effects of steroid usage in pediatric transplantation has led to steroid minimization or steroid-free transplantation. In this study, we report results after complete steroid avoidance in renal transplantation in the period 1994-2009. We evaluate...... in the youngest (renal transplantation is safe and protects against steroid-induced obesity and short stature....... the effects of complete steroid avoidance on allograft function, BMI, and linear growth. The majority of transplanted children were induced with antithymocyte globulin and immunosuppressed with a calcineurin inhibitor and mycophenolate mofetil. Steroids were given only when rejection occurred or due...

  19. Effect of ultraviolet irradiation on free radical scavenging activity of immunosuppressants used in lung transplantation and comparative electron paramagnetic resonance study of kinetics of their interactions with model free radicals.

    Science.gov (United States)

    Stanjek-Cichoracka, A; Żegleń, S; Ramos, P; Pilawa, B; Wojarski, J

    2018-06-01

    The immunosuppressive drugs used in solid organ transplantation or autoimmunological processes were studied by electron paramagnetic resonance (EPR) spectroscopy to estimate their free radical scavenging activity. The interactions of immunosuppressants with free radicals were examined by an X-band (9.3 GHz) EPR spectroscopy and a model of DPPH free radicals. The EPR spectra of DPPH and DPPH interacting with individual drugs were compared. Kinetic studies were performed, and the effect of ultraviolet (UV) irradiation on the free radical scavenging activity of the tested drugs was determined. The free radical scavenging activity of non-irradiated drugs decreased in the order: rapamycin > mycophenolate mofetil > ciclosporin > tacrolimus. UV irradiation increased the free radical scavenging activity of all the tested immunosuppressive drugs, and the effect was highest for tacrolimus. For the non-irradiated samples, the speed of free radical interactions decreased in the order: ciclosporin > tacrolimus > mycophenolate mofetil > rapamycin. UV irradiation only slightly affected the speed of interactions of the immunosuppressive drugs with the model DPPH free radicals. Electron paramagnetic resonance spectroscopy is useful for obtaining information on interactions of immunosuppressive drugs with free radicals. We hypothesized that the long-term immunosuppressive effects of these drugs after transplantation or during autoimmune disorders may be mediated by anti-inflammatory action in addition to the known receptor/cell cycle inhibition. © 2018 John Wiley & Sons Ltd.

  20. Idiopathic Nephrotic Syndrome in Childhood: A Retrospective Analysis of Two Hundred and Eighty Nine Patients

    Directory of Open Access Journals (Sweden)

    Kenan Yılmaz

    2017-12-01

    Full Text Available Aim: In this study, we aimed to evaluate the demographic and histopathological characteristics and response to medications in children with idiopathic nephrotic syndrome in Turkey. Methods: We reviewed medical records of patients older than one year, who were newly diagnosed with nephrotic syndrome and had been followed for at least one year in our department between November 1994 and March, 2013. Results: A total of 289 children (169 boys were included in the study. Fifty theree patients (18.4% were with steroid-resistant nephrotic syndrome, 33 (11.4% with frequently relapsing nephrotic syndrome and 53 (18.4% were with steroid-dependent nephrotic syndrome. Cyclosporine A (CsA, cyclophosphamide, mycophenolate mofetil, levamisole, azathioprine, and rituximab were used as steroid-sparing agents in some patients. The number of patients who were responder to steroid and to CsA was similar. Majority of patients with steroid-resistant nephrotic syndrome were also resistant to mycophenolate mofetil and CsA. Conclusion: There was a high prevalence of minimal change disease based on kidney biopsy especially in boys younger than six years of age and response to steroid and CsA was almost similar.

  1. Perspective on future therapy of vasculitis.

    Science.gov (United States)

    Boumpas, D T; Kritikos, H D; Daskalakis, N G

    2000-10-01

    This article summarizes recent advances in the management of various vasculitic syndromes and discusses potential new therapies based on a better understanding of their pathogenesis and natural history. Current efforts for optimization of testing for antineutrophil cytoplasmic antibodies and improvement of diagnostic criteria will certainly have a significant impact on future therapy. Biologic agents such as interferon-alpha are already in use in various vasculitides, whereas others, such as inhibitors of tumor necrosis factor-alpha, are in phase I clinical trials. Agents that selectively inhibit distinct steps in the pathogenesis of vasculitis are in preclinical or early clinical stages of development. Newer (mycophenolate mofetil, leflunamide) or older (methotrexate, azathioprine) immunosuppresive agents are finding new roles in the management of vasculitides. For patients with severe vasculitis, short-term use of cytotoxic agents, such as cyclophosphamide, alone or in combination with biologic agents, may expedite remission, which could then be better maintained with other, less toxic (and less expensive) immunosuppressive agents, such as methotrexate, azathioprine, mycophenolate mofetil, and leflunamide. For patients with mild or moderately severe vasculitis, these latter agents alone may be adequate. New therapeutic studies in vasculitis should better address the impact of therapy on health-related quality of life and its long-term toxicity.

  2. The influence of intrauterine exposure to immunosuppressive treatment on changes in the immune system in juvenile Wistar rats.

    Science.gov (United States)

    Kabat-Koperska, Joanna; Kolasa-Wołosiuk, Agnieszka; Wojciuk, Bartosz; Wojciechowska-Koszko, Iwona; Roszkowska, Paulina; Krasnodębska-Szponder, Barbara; Paczkowska, Edyta; Safranow, Krzysztof; Gołembiewska, Edyta; Machaliński, Bogusław; Ciechanowski, Kazimierz

    2016-01-01

    In our study, we assessed the impact of immunosuppressive drug combinations on changes in the immune system of juvenile Wistar rats exposed to these drugs during pregnancy. We primarily concentrated on changes in two organs of the immune system - the thymus and the spleen. The study was conducted on 40 (32+8) female Wistar rats administered full and half dose of drugs, respectively, subjected to regimens commonly used in therapy of human kidney transplant recipients ([1] cyclosporine A, mycophenolate mofetil, and prednisone; [2] tacrolimus, mycophenolate mofetil, and prednisone; [3] cyclosporine A, everolimus, and prednisone). The animals received drugs by oral gavage 2 weeks before pregnancy and during 3 weeks of pregnancy. There were no statistically significant differences in the weight of the thymus and spleen, but changes were found in the results of blood hematology, cytometry from the spleen, and a histologic examination of the examined immune organs of juvenile Wistar rats. In the cytokine assay, changes in the level of interleukine 17 (IL-17) after increasing amounts of concanavaline A were dose-dependent; the increase of IL-17 was blocked after administration of higher doses of immunosuppressive drugs. However, after a reduction of doses, its increase resumed. Qualitative, quantitative, and morphological changes in the immune system of infant rats born to pharmacologically immunosuppressed females were observed. Thymus structure, spleen composition, and splenocyte IL-17 production were mostly affected in a drug regimen-dependent manner.

  3. New and emerging trends in the treatment of atopic dermatitis

    Directory of Open Access Journals (Sweden)

    Christina M Gelbard

    2009-01-01

    Full Text Available Christina M Gelbard1, Adelaide A Hebert1,21Departments of Dermatology; 2Pediatrics, University of Texas-Houston, Houston, TX, USAAbstract: Atopic dermatitis is a chronic, inflammatory skin condition that affects 10% to 20% of children and 1% to 3% of adults in the US. Symptoms often result in sleeplessness, psychological stress, poor self-esteem, anxiety, and poor school or work performance. The cost of atopic dermatitis is estimated to be US$0.9 to 3.8 billion every year. Topical steroids are first-line treatment for atopic dermatitis, and recent advances in vehicle technologies have resulted in improved patient tolerability and compliance. Topical calcineurin inhibitors are also safe and effective topical treatments for atopic dermatitis, and provide an additional therapeutic option for patients with this disease. Systemic immunomodulators are used in the treatment of severe refractory disease. Cyclosporine, methotrexate, azathioprine, mycophenolate mofetil, and interferon gamma have been used in the management of severe atopic dermatitis. This review highlights the current and emerging trends in the treatment of atopic dermatitis.Keywords: atopic dermatitis, topical corticosteroids, calcineurin inhibitors, methotrexate, cyclosporine, mycophenolate mofetil, IFN-γ

  4. 免疫抑制剂对移植术后血脂异常的研究%Research of immunosuppressant on dyslipidemia after organ transplantation

    Institute of Scientific and Technical Information of China (English)

    应亮; 邱丰

    2012-01-01

    Cardiovascular and cerebrovascular complications is one of the major causes of transplanted organ death for the long-term survival patients with organ transplantation. In many factors of the resulting cardiac cerebral arteriosclerosis, hy-perlipidemia is one of the most important reasons. The immunosuppressive effects on serum lipids were reviewed in detail in this paper, including Corticosteroids, Cyclosporine, Tacrolimus, Sirolimus, Mycophenolate Mofetil, Azathioprine, and ultimately Mycophenolate Mofetil is one of the drugs which has minimal impact on blood lipids.%心脑血管合并症是导致长期存活器官移植患者移植器官功能死亡的主要原因之一.在导致心脑动脉硬化的诸多因素中,高脂血症是其中最重要的原因.文章详细地论述了不同免疫抑制剂对血脂的影响,包括皮质类固醇激素、环孢霉素、他克莫司、西罗莫司、吗替麦考酚酯、硫唑嘌呤等,最终发现吗替麦考酚酯是对血脂影响最小的药物之一.

  5. COMPARATIVE ANALYSIS OF SOLUBLE OF CD40 LIGAND LEVELS IN HEART RECIPIENTS TREATED WITH CYCLOSPORINE A AND TACROLIMUS

    Directory of Open Access Journals (Sweden)

    O. P. Shevchenko

    2012-01-01

    Full Text Available Soluble form of CD40L is platelet activating factor, which is a marker of inflammation and thrombosis. Elevated levels of sCD40L before the heart transplantation are associated with the risk of early development of cardiova- scular complications. The study included 54 patients who had received heart transplants. All recipients received a triple heart immu- nosuppressive therapy, including methylprednisolone, mycophenolate mofetil and cyclosporine A (20 recipients or methylprednisolone, mycophenolate mofetil and tacrolimus (34 recipients. Patients were not differed by age, gender, etiology of heart failure before heart transplantation (p > 0,05. In the first group of transplant recipients, the relative risk of cardiovascular events with high sCD40L levels before transplantation was 3 2 (95% CI 1,4; 12,0. In the second group of recipients, respectively, 2.69 (95% CI 1,1; 8,5. SCD40L level after heart transplan- tation was significantly higher for patients receiving cyclosporine (P < 0.05. Increasing concentrations of sCD40L are associated with a higher incidence of cardiovascular complications. 

  6. Results of a multicenter prospective clinical study in Japan for evaluating efficacy and safety of desensitization protocol based on rituximab in ABO-incompatible kidney transplantation.

    Science.gov (United States)

    Takahashi, Kota; Saito, Kazuhide; Takahara, Shiro; Fuchinoue, Shohei; Yagisawa, Takashi; Aikawa, Atsushi; Watarai, Yoshihiko; Yoshimura, Norio; Tanabe, Kazunari; Morozumi, Kunio; Shimazu, Motohide

    2017-08-01

    Deceased organ donations are rare in Japan, with most kidney transplants performed from a limited number of living donors. Researchers have thus developed highly successful ABO-incompatible transplantation procedures, emphasizing preoperative desensitization and postoperative immunosuppression. A recent open-label, single-arm, multicenter clinical study prospectively examined the efficacy and safety of rituximab/mycophenolate mofetil desensitization in ABO-incompatible kidney transplantation without splenectomy. Mycophenolate mofetil and low dose steroid were started 28 days pretransplant, followed by two doses of rituximab 375 mg/m 2 at day -14 and day -1, and postoperative immunosuppression with tacrolimus or ciclosporin and basiliximab. The primary endpoint was the non-occurrence rate of acute antibody-mediated rejection. Patient survival and graft survival were monitored for 1 year posttransplant. Eighteen patients received rituximab and underwent ABO-incompatible kidney transplantation. CD19-positive peripheral B cell count decreased rapidly after the first rituximab infusion and recovered gradually after week 36. The desensitization protocol was tolerable, and most rituximab-related infusion reactions were mild. No anti-A/B antibody-mediated rejection occurred with this series. One patient developed anti-HLA antibody-mediated rejection (Banff 07 type II) on day 2, which was successfully managed. Patient and graft survival were both 100 % after 1 year. Our desensitization protocol was confirmed to be clinically effective and with acceptable toxicities for ABO-I-KTx (University Hospital Medical Information Network Registration Number: UMIN000006635).

  7. Assessing the clinical effectiveness of an algorithmic approach for mucosal lichen planus (MLP): A retrospective review.

    Science.gov (United States)

    Ashack, Kurt A; Haley, Laura L; Luther, Chelsea A; Riemer, Christie A; Ashack, Richard J

    2016-06-01

    Mucosal lichen planus (MLP) is a therapeutic challenge in need of a new treatment approach because of its debilitating effect on patient's quality of life. We sought to evaluate a standardized treatment plan for patients with MLP. A second objective was to describe the effect of mycophenolate mofetil in this patient population. The study retrospectively analyzed 53 patients with MLP treated using a standardized algorithm. The number of MLP lesions, disease activity, and pain at the last visit were compared with baseline scores determined at the initial visit. Results were analyzed using the paired samples t test and confirmed with the Wilcoxon matched pairs signed rank test. The average number of lesions was reduced from 3.77 to 1.67 (P < .001). The average disease activity was reduced from 2.73 to 0.90 (P < .001). Average pain reported decreased from 2.03 to 1.03 (P < .001). This study was a retrospective analysis of a small patient population. There was no universal symptom severity scale used at the time of treatment for some patients. The standardized treatment plan reduced symptoms for patients with MLP. Mycophenolate mofetil appears to be a reasonable treatment option for these patients. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  8. Conversion from calcineurin inhibitors to sirolimus of recipients with chronic kidney graft disease grade iii for a period 2003-2011

    Directory of Open Access Journals (Sweden)

    Ignjatović Ljiljana

    2013-01-01

    Full Text Available Background/Aim. Tremendous breakthrough in solid organ transplantation was made with the introduction of calcineurin inhibitors (CNI. At the same time, they are potentially nephrotoxic drugs with influence on onset and progression of renal graft failure. The aim of this study was to evaluate the outcome of a conversion from CNIbased immunosuppressive protocol to sirolimus (SRL in recipients with graft in chronic kidney disease (CKD grade III and proteinuria below 500 mg/day. Methods. In the period 2003-2011 24 patients (6 famale and 18 male, mean age 41 ± 12.2 years, on triple immunosuppressive therapy: steroids, antiproliferative drug [mycophenolate mofetil (MMF or azathiopirine (AZA] and CNI were switched from CNI to SRL and followe-up for 76 ± 13 months. Nine patients (the group I had early postransplant conversion after 4 ± 3 months and 15 patients (the group II late conversion after 46 ± 29 months. During the regular outpatient controls we followed graft function through the serum creatinine and glomerular filtration rate (GFR, proteinuria, lipidemia and side effects. Results. Thirty days after conversion, in all the patients GFR, proteinuria and lipidemia were insignificantly increased. In the first two post-conversion months all the patients had at least one urinary or respiratory infection, and 10 patients reactivated cytomegalovirus (CMV infection or disease, and they were successfully treated with standard therapy. After 21 ± 11 months 15 patients from both groups discontinued SRL therapy due to reconversion to CNI (10 patients and double immunosuppressive therapy (3 patients, return to hemodialysis (1 patient and death (1 patient. Nine patients were still on SRL therapy. By the end of the follow-up they significantly improved GFR (from 53.2 ± 12.7 to 69 ± 15 mL/min, while the increase in proteinuria (from 265 ± 239 to 530.6 ± 416.7 mg/day and lipidemia (cholesterol from 4.71 ± 0.98 to 5.61 ± 1.6 mmol/L and triglycerides

  9. Mycophenolate plus methylprednisolone versus methylprednisolone alone in active, moderate-to-severe Graves' orbitopathy (MINGO)

    DEFF Research Database (Denmark)

    Kahaly, George J; Riedl, Michaela; König, Jochem

    2018-01-01

    BACKGROUND: European guidelines recommend intravenous methylprednisolone as first-line treatment for active and severe Graves' orbitopathy; however, it is common for patients to have no response or have relapse after discontinuation of treatment. We aimed to compare the efficacy and safety of add...

  10. Brevianamides and Mycophenolic Acid Derivatives from the Deep-Sea-Derived Fungus Penicillium brevicompactum DFFSCS025

    Directory of Open Access Journals (Sweden)

    Xinya Xu

    2017-02-01

    Full Text Available Four new compounds (1–4, including two brevianamides and two mycochromenic acid derivatives along with six known compounds were isolated from the deep-sea-derived fungus Penicillium brevicompactum DFFSCS025. Their structures were elucidated by spectroscopic analysis. Moreover, the absolute configurations of 1 and 2 were determined by quantum chemical calculations of the electronic circular dichroism (ECD spectra. Compound 9 showed moderate cytotoxicity against human colon cancer HCT116 cell line with IC50 value of 15.6 μM. In addition, 3 and 5 had significant antifouling activity against Bugula neritina larval settlement with EC50 values of 13.7 and 22.6 μM, respectively. The NMR data of 6, 8, and 9 were assigned for the first time.

  11. Photoletter to the editor: Oral ulceration in pyoderma gangrenosum.

    LENUS (Irish Health Repository)

    Verma, Saroj

    2012-02-01

    A 65-year-old woman presented with widespread necrotising cutaneous ulceration and oral involvement. Past history included rheumatoid arthritis, and a left nephrectomy.Examination revealed multiple violaceous undermined ulcers. Blood investigations showed an acute inflammatory response. Skin histopathology showed epidermal ulceration with acute and chronic inflammation. Direct immunofluorescence was negative. A diagnosis of pyoderma gangrenosum with oral involvement was made. Mycophenolate mofetil therapy resulted in complete resolution of her pyoderma gangrenosum. Her treatment was complicated by a left proteus mirabilis psoas abscess. This resolved following four weeks of antibiotics.Pyoderma gangrenosum with oral involvement is rare but has been linked with inflammatory bowel disease and hematological disorders. Oral pyoderma gangrenosum has not previously been described in rheumatoid arthritis. Primary psoas abscess is rare but can develop in immunocompromised patients. Proteus mirabilis has been reported in patients years after nephrectomy. This is a rare case of pyoderma gangrenosum with oral involvement.

  12. Current topics in autoimmune hepatitis.

    Science.gov (United States)

    Muratori, Luigi; Muratori, Paolo; Granito, Alessandro; Pappas, Giorgios; Cassani, Fabio; Lenzi, Marco

    2010-11-01

    Autoimmune hepatitis is a chronic liver disease of unknown aetiology characterized by interface hepatitis, hypergammaglobulinaemia and circulating autoantibodies. In the last decade a number of advancements have been made in the field of clinical and basic research: the simplified diagnostic criteria, the complete response defined as normalization of transaminase levels, the molecular identification of the antigenic targets of anti-liver cytosol antibody type 1 and anti-soluble liver antigen, the detection of anti-actin antibodies, the description of de novo autoimmune hepatitis after liver transplantation for non-autoimmune liver diseases, the characterization of autoimmune hepatitis with overlapping features of primary biliary cirrhosis or primary sclerosing cholangitis, the preliminary experience with novel treatment strategies based on cyclosporine, mycophenolate mofetil and budesonide, the role played by "impaired" regulatory T cells and the development of novel animal models of autoimmune hepatitis. Copyright © 2010 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  13. [Clinical views from the forefront of immunosuppressive drugs].

    Science.gov (United States)

    Kobayashi, Eiji

    2005-11-01

    Recently, many immunosuppressants have been developed and some of them have already been introduced in clinical organ transplantation. With a new concept of immunoregulation, which focuses on prevention of rejection and over-immunosuppression, the latest protocol has been conducted. Chimeric or humanized antibodies targeting the lymphocyte surface molecule such as CD19, 20, 25, 40, and 52 are administrated in the induction phase, and calcineurin inhibitors (cyclosporin and tacrolimus) are used as key drugs. For tapering the doses of them, the combined application of anti-metabolic agents of azathioprine, mizoribine, or mycophenolate mofetil (MMF) has been proved effective. Lymphocyte forming drugs induce unique immunoregulation, targeting at sphingosine 1-phosphate (SlP) receptors. FTY720 is now in the procedure of clinical trial to compare with MMF. KRP203 is also a candidate for more specific SIP receptor agonist. In this issue, I reviewed the recent immunosuppressive strategy and focused on the advance of novel immunosuppressive drugs.

  14. General principles for the treatment of non-infectious uveitis.

    Science.gov (United States)

    Díaz-Llopis, Manuel; Gallego-Pinazo, Roberto; García-Delpech, Salvador; Salom-Alonso, David

    2009-09-01

    Ocular inflammatory disorders constitute a sight-threatening group of diseases that might be managed according to their severity. Their treatment guidelines experience constant changes with new agents that improve the results obtained with former drugs. Nowadays we can make use of a five step protocol in which topical, periocular and systemic corticosteroids remain as the main therapy for non infectious uveitis. In addition, immunosuppresive drugs can be added in order to enhance the anti-inflammatory effects and to develop the role of corticosteroid-saving agents. These can be organized in four other steps: Cyclosporine and Methotrexate in a second one; Azathioprine, Mycophenolate Mofetil and Tacrolimus in a third step; biological anti-TNF drugs in fourth position; and a theoretical last one with Cyclophosphamide and Chlorambucil. In the present review we go through the main characteristics and complications of all these treatments and make a rational of this five-step treatment protocol for non infectious posterior uveitis.

  15. Generalized subcutaneous edema as a rare manifestation of dermatomyositis: clinical lesson from a rare feature.

    LENUS (Irish Health Repository)

    Haroon, Muhammad

    2011-04-01

    Generalized subcutaneous edema is a very rare manifestation of inflammatory myopathies. A 61-year-old woman presented with classic signs and symptoms of dermatomyositis. She was also noted to have generalized edema that was so florid that an alternative diagnosis was considered. Her disease was resistant to corticosteroids, azathioprine, and mycophenolate mofetil. Intravenous administration of immunoglobulins was started because of marked worsening of her disease-muscle weakness, generalized anasarca, and involvement of her bulbar muscles. This led to dramatic resolution of her subcutaneous edema and significant improvement of her skin and muscle disease. As the initial screen for malignancy was negative, a positron emission tomography-computed tomography scan was requested, which interestingly showed a metabolically active cervical tumor. Anasarca is an unusual manifestation of dermatomyositis. In treatment-refractory cases, it seems reasonable to consider positron emission tomography scan in excluding underlying malignant disease.

  16. Multifocal Choroiditis with Retinal Vasculitis, Optic Neuropathy, and Keratoconus in a Young Saudi Male.

    Science.gov (United States)

    Dhafiri, Yousef; Al Rubaie, Khalid; Kirat, Omar; May, William N; Nguyen, Quan D; Kozak, Igor

    2017-01-01

    The purpose of this study is to describe an association of unilateral multifocal choroiditis (MFC), retinal vasculitis, optic neuropathy, and bilateral keratoconus in a young Saudi male. A 27-year-old male patient with stable bilateral keratoconus presented with a painless vision loss in his left eye. Ophthalmic examinations revealed multiple foci of idiopathic chorioretinitis, retinal vasculitis, and mild optic disc leakage on fluorescein angiography, all of which resolved on systemic therapy with mycophenolate mofetil and prednisone after 3 months. Systemic medication was stopped after 8 months. One year after presentation, patient's visual acuity has improved and remained stable. Systemic immunomodulatory therapy can be effective in managing and leading to resolution of MFC, retinal vasculitis, and optic disc leak in young patients.

  17. Morphea in Childhood: An Update.

    Science.gov (United States)

    Aranegui, B; Jiménez-Reyes, J

    2018-05-01

    Morphea is an inflammatory, fibrosing skin disorder. When it occurs in childhood, it is also known as localized juvenile scleroderma. It is more common in girls and typically appears around the age of 5 to 7 years. According to a recent classification system, morphea is divided into 5 types: circumscribed (plaque), linear, generalized, pansclerotic, and mixed. Approximately 40% of patients present extracutaneous manifestations. Childhood morphea is treated with phototherapy, oral or topical calcitriol, topical tacrolimus 0.1%, methotrexate, topical or systemic corticosteroids, mycophenolate mofetil, bosentán, and topical imiquimod 5%. A variety of measuring tools are used to monitor response to treatment. Few prognostic studies have been conducted, but findings to date suggest that the disease tends to run a chronic or intermittent-recurrent course and frequently causes sequelae. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Aquaporin-4 serostatus does not predict response to immunotherapy in neuromyelitis optica spectrum disorders.

    Science.gov (United States)

    Mealy, Maureen A; Kim, Su-Hyun; Schmidt, Felix; López, Reydmar; Jimenez Arango, Jorge A; Paul, Friedemann; Wingerchuk, Dean M; Greenberg, Benjamin M; Kim, Ho Jin; Levy, Michael

    2017-08-01

    Debate exists about whether neuromyelitis optica spectrum disorder seronegative disease represents the same immune-mediated attack on astrocytic aquaporin-4 as in seropositive disease. We investigated whether response to common treatments for neuromyelitis optica spectrum disorder differed by serostatus, as assessed by change in annualized relapse rate. We performed a multicenter retrospective analysis of 245 patients with neuromyelitis optica spectrum disorder who were treated with either rituximab or mycophenolate mofetil as their first-line immunosuppressive treatment for disease prevention. Patients were followed for a minimum of 6 months following treatment initiation. In those started on rituximab, the pre-treatment annualized relapse rates for seropositive and seronegative patients were 1.81 and 1.93, respectively. On-treatment annualized relapse rates significantly declined to 0.32 (seropositive; p optica spectrum disorder patients, treatment was effective regardless of serostatus. This suggests that treatment should not differ when considering these treatments.

  19. Standard and biological treatment in large vessel vasculitis: guidelines and current approaches.

    Science.gov (United States)

    Muratore, Francesco; Pipitone, Nicolò; Salvarani, Carlo

    2017-04-01

    Giant cell arteritis and Takayasu arteritis are the two major forms of idiopathic large vessel vasculitis. High doses of glucocorticoids are effective in inducing remission in both conditions, but relapses and recurrences are common, requiring prolonged glucocorticoid treatment with the risk of the related adverse events. Areas covered: In this article, we will review the standard and biological treatment strategies in large vessel vasculitis, and we will focus on the current approaches to these diseases. Expert commentary: The results of treatment trials with conventional immunosuppressive agents such as methotrexate, azathioprine, mycophenolate mofetil, and cyclophosphamide have overall been disappointing. TNF-α blockers are ineffective in giant cell arteritis, while observational evidence and a phase 2 randomized trial support the use of tocilizumab in relapsing giant cell arteritis. Observational evidence strongly supports the use of anti-TNF-α agents and tocilizumab in Takayasu patients with relapsing disease. However biological agents are not curative, and relapses remain common.

  20. Neuropsychiatric Systemic Lupus Erythematosus

    Science.gov (United States)

    Popescu, Alexandra; Kao, Amy H

    2011-01-01

    Neuropsychiatric systemic lupus erythematosus (NPSLE) is the least understood, yet perhaps the most prevalent manifestation of lupus. The pathogenesis of NPSLE is multifactorial and involves various inflammatory cytokines, autoantibodies, and immune complexes resulting in vasculopathic, cytotoxic and autoantibody-mediated neuronal injury. The management of NPSLE is multimodal and has not been subjected to rigorous study. Different treatment regimens include nonsteroidal anti-inflammatory drugs, anticoagulation, and immunosuppressives such as cyclophosphamide, azathioprine, mycophenolate mofetil, and methotrexate. For refractory NPSLE, intravenous immunoglobulin (IVIG), plasmapheresis, and rituximab have been used. Adjunctive symptomatic treatment complements these therapies by targeting mood disorders, psychosis, cognitive impairment, seizures or headaches. Several new biological agents are being tested including Belimumab, a human monoclonal antibody that targets B lymphocyte stimulator. This review focuses on the pathophysiology, treatment, and new potential therapies for neuropsychiatric manifestations of systemic lupus erythematosus. PMID:22379459

  1. Therapeutic Plasmapheresis in Kidney Transplantation

    Directory of Open Access Journals (Sweden)

    Zeynep Kendi Celebi

    2013-02-01

    Full Text Available In 1960's, with succesfully renal transplantations, acute rejection became to be a serious problem for graft survival. From 1965 to 2010, with the introduction of new immunosuppressant agents such as cyclosporine, mycophenolate mofetile and tacrolimus, the acute rejection rates declined from 80% to 10% . There is an ongoing gradual improvement in allograft survival. Use of Therapeutic plasma exchange (TPE is not evidence based treatment, but TPE is necessary for pre- and also post transplantation in patients with DSA. TPE is also a main treatment for antibody mediated rejection (AMR , but in clinical practice the duration and frequency of TPE and individual difference of antibody production is unclear. There is a requirement for more specific antibody elimination. Further randomised controlled studies are needed to elucidate TPE use before and after kidney transplantation. [Dis Mol Med 2013; 1(1.000: 8-10

  2. Treatment of pediatric chronic inflammatory demyelinating polyneuropathy: Challenges, controversies, and questions

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    Jay Desai

    2015-01-01

    Full Text Available Pediatric chronic inflammatory demyelinating polyneuropathy (CIDP is an uncommon acquired disorder of unknown cause, presumed to have an immunological basis. We report 20 patients seen at Children′s Hospital Los Angeles over a period of 10 years. The outcome of our patients was favorable in a vast majority with good response to various treatments instituted. However, residual neurologic deficit was common. The choice of treatment modality was empirical and selected by the treating neurologist. Intravenous immunoglobulin (IVIG and corticosteroids were most commonly utilized for treatment. Plasmapheresis, mycophenolate mofetil, rituximab, cyclophosphamide, azathioprine, and abatacept were added if the patients were refractory to IVIG or became corticosteroid dependent. The spectrum of disease severity ranged from a single monophasic episode, to multiphasic with infrequent relapses with good response to IVIG, to progressive disease refractory to multiple therapies.

  3. Pediatric renal transplantation in a highly sensitised child-8 years on.

    LENUS (Irish Health Repository)

    Quinlan, Catherine

    2012-01-26

    Highly sensitised children have markedly reduced chances of receiving a successful deceased donor renal transplant, increased risk of rejection, and decreased graft survival. There is limited experience with the long-term followup of children who have undergone desensitization. Following 2 failed transplants, our patient was highly sensitised. She had some immunological response to intravenous immunoglobulin (IVIg) but this was not sustained. We developed a protocol involving sequential therapies with rituximab, IVIg, and plasma exchange. Immunosuppressant therapy at transplantation consisted of basiliximab, tacrolimus, mycophenolate mofetil, and steroids. At the time of transplantation, historical crossmatch was ignored. Current CDC crossmatch was negative, but T and B cell flow crossmatch was positive, due to donor-specific HLA Class I antibodies. Further plasma exchange and immunoglobulin therapy were given pre- and postoperatively. Our patient received a deceased donor-kidney-bearing HLA antigens to which she originally had antibodies, which would have precluded transplant. The graft kidney continues to function well 8 years posttransplant.

  4. Methods, strengths, weaknesses, and limitations of bioequivalence tests with special regard to immunosuppressive drugs.

    Science.gov (United States)

    van Gelder, Teun; Gabardi, Steven

    2013-08-01

    Within the field of solid organ transplantation, the patents for a number of immunosuppressive drugs have expired in the last few years. Tacrolimus, cyclosporine, and mycophenolate mofetil are now available as generic drugs. In some countries, the market penetration of these generic formulations is as high as 70%, whereas in some other countries, this figure is below 10%. Several professional societies have published position papers on the risks and benefits of generic substitution of immunosuppressive drugs. It often appears that transplant professionals are not fully aware of the requirements for registration of generic drugs. This article describes the registration requirements with a focus on bioequivalence testing, the strengths and weaknesses in this process, and the differences between Europe and the US. © 2013 The Authors Transplant International © 2013 European Society for Organ Transplantation. Published by Blackwell Publishing Ltd.

  5. Simultaneous Hodgkin′s disease and kaposi sarcoma in a renal transplant recipient

    Directory of Open Access Journals (Sweden)

    Yaich S

    2010-01-01

    Full Text Available A 38-year-old women underwent first cadaver kidney transplantation. Her panel re-active antibody was 0%, and she had never previously been transfused nor pregnant. She received induction therapy with antithymoglobulin (ATG as standard protocol and maintained on immuno-suppressive treatment of cyclosporine A, mycophenolate mofetil (MMF, and prednisone. Nine months after transplantation, she presented with anorexia, asthenia and weight loss. Cutaneous Ka-posi′s sarcoma and a Hodgkin disease were diagnosed. MMF was discontinued and cyclosporin A was switched to sirolimus. She also received a poly-chemotherapy associated with 4 courses of rituximab. Twelve months later, the patient had normal graft function and both malignancies were in complete remission.

  6. Hemorrhagic Tamponade as Initial Manifestation of Systemic Lupus with Subsequent Refractory and Progressive Lupus Myocarditis Resulting in Cardiomyopathy and Mitral Regurgitation

    Directory of Open Access Journals (Sweden)

    Nicole Marijanovich

    2018-01-01

    Full Text Available Systemic lupus erythematosus (SLE is a heterogeneous autoimmune disease with a wide range of clinical and serological manifestations. Cardiac disease among patients with SLE is common and can involve the pericardium, myocardium, valves, conduction system, and coronary arteries. We are reporting a case of SLE in a young woman that is unique is unique in that initial symptoms consisted of pericarditis and hemorrhagic tamponade which remained progressive and resistant to aggressive immunosuppressive treatment and led to severe cardiomyopathy (ejection fraction of 25% and severe (+4 mitral regurgitation. Her immunosuppressive treatment included hydroxychloroquine, high-dose steroids, intravenous immunoglobulins, azathioprine, and mycophenolate mofetil. Her disease progression was felt to be due to underlying uncontrolled SLE because the complement levels remained persistently low throughout the entire course and PET Myocardial Perfusion and Viability study showed stable persistent active inflammation. Eventually, she was treated with cyclophosphamide which led to improvement in ejection fraction to 55% with only mild mitral regurgitation.

  7. Renal disease masquerading as pyrexia of unknown origin

    Directory of Open Access Journals (Sweden)

    D Korivi

    2013-01-01

    Full Text Available Pyrexia of unknown origin is a challenging clinical problem. Infections, malignancies, and connective tissue diseases form the major etiologies for this condition. We report a case of a 57-year-old diabetic male who presented with fever of unknown origin for several months. The course of investigations led to a kidney biopsy which clinched the cause of his fever as well as the underlying diagnosis. The light microscopy findings of expansile storiform fibrosis with a dense inflammatory infiltrate suggested the diagnosis which was confirmed by positive staining of Immunoglobulin G4, the dense lympho-plasmacytic infiltrate and elevated serum IgG4 concentrations. A course of steroids followed by mycophenolate mofetil as maintenance immunosuppression rendered the patient afebrile with improvement of renal function.

  8. Toxic Epidermal Necrolysis-Like Lesions and Systemic Lupus Erythematosus Possibly Triggered by Sulfasalazine

    Directory of Open Access Journals (Sweden)

    Simon Krabbe

    2016-01-01

    Full Text Available This case report describes a patient with arthritis of the large joints, bilateral sacroiliitis, and positive anti-SSA and anti-dsDNA antibody, who received sulfasalazine and shortly thereafter became critically ill. He developed toxic epidermal necrolysis, hemolytic anemia, lymphopenia, markedly elevated ferritin, and muscle wasting. A diagnosis of systemic lupus erythematosus was made, and mycophenolate mofetil and systemic glucocorticoids brought this severe disease under control. Toxic epidermal necrolysis-like lesions and hemophagocytic syndrome have been reported as manifestations of systemic lupus erythematosus. This patient possibly had spondyloarthritis or an undifferentiated connective tissue disease at presentation, and we suggest, based on the timing of events, that sulfasalazine may have acted as a trigger of the severe disease manifestations.

  9. Anti-Ma2-associated encephalitis with normal FDG-PET: a case of pseudo-Whipple's disease.

    Science.gov (United States)

    Castle, James; Sakonju, Ai; Dalmau, Josep; Newman-Toker, David E

    2006-10-01

    A 39-year-old man presented with a history of several months of progressive personality changes, social withdrawal, bradykinesia, mutism, dysphagia, worsening gait, and difficulty with daily living activities. Examination revealed an atypical parkinsonian appearance with incomplete supranuclear ophthalmoplegia and an unusual oculomotor disorder characterized by both low-amplitude, intermittent opsoclonus, and slow, nystagmoid intrusions. Routine laboratory testing, autoimmune and infectious serologies, brain MRI, lumbar puncture, electroencephalogram, whole-body CT scan, paraneoplastic serologies, small bowel biopsy, 18F-fluorodeoxyglucose positron emission tomography CT scan, brain biopsy, and testicular ultrasound. Anti-Ma2 paraneoplastic encephalitis in association with metastatic testicular cancer; initially misdiagnosed as CNS Whipple's disease. Corticosteroids, intravenous immunoglobulins, orchiectomy, muscle relaxants, mycophenolate mofetil, plasmapheresis, and bleomycin, etoposide and platinum chemotherapy.

  10. Parvovirus B19 induced lupus-like syndrome with nephritis.

    Science.gov (United States)

    Georges, Elodie; Rihova, Zuzana; Cmejla, Radek; Decleire, Pierre-Yves; Langen, Corinne

    2016-12-01

    We report a case of a 65-year-old man who developed an acute illness with fever, arthralgia and nephritic syndrome. Antinuclear antibodies were slightly positive and complement levels were low. Renal biopsy showed exudative diffuse proliferative endocapillary glomerulonephritis with diffuse immunoglobulin (IgG, IgA, IgM) and complement deposition (C3d, C4d, C1q) on immunofluorescence. The patient was first treated with corticosteroids and mycophenolate mofetil for suspected lupus with WHO class IV glomerulonephritis. The diagnosis was questioned and a diagnosis of parvovirus B19-associated nephritis was made based on elevation of serum IgM antibodies for parvovirus B19 and detection of parvovirus B19 DNA on renal biopsy. The immunosuppressive treatment was stopped and progressive spontaneous regression of clinical and laboratory abnormalities was observed. We conclude that human parvovirus B19 infection should be considered as a cause of lupus-like symptomatology and acute glomerulonephritis.

  11. Anaemia and fever in kidney transplant. The role of human parvovirus B19

    Directory of Open Access Journals (Sweden)

    Yanet Parodis López

    2017-03-01

    We report the case of a 65 year-old man with a history of deceased donor renal transplant in September 2014. At 38 days after the transplant, the patient presented progressive anaemia that was resistant to erythropoiesis-stimulating agents. At 64 days after transplant, hyperthermia occurred with progressive deterioration of the patient's general condition. The viral serology and the first blood PCR for human parvovirus B19 were both negative. At 4 months and 19 days after, a bone marrow biopsy was conducted, showing giant erythroblasts with nuclear viral inclusions that were compatible with parvovirus; a PCR in the tissue confirmed the diagnosis. A second blood PCR was positive for parvovirus. After treatment with intravenous immunoglobulin and the temporary discontinuation of mycophenolate mofetil, a complete remission of the disease occurred, although the blood PCR for parvovirus B19 remained positive, so monitoring is necessary for future likely recurrence.

  12. Incidence of Posttransplantation Diabetes Mellitus in De Novo Kidney Transplant Recipients Receiving Prolonged-Release Tacrolimus-Based Immunosuppression With 2 Different Corticosteroid Minimization Strategies: ADVANCE, A Randomized Controlled Trial.

    Science.gov (United States)

    Mourad, Georges; Glyda, Maciej; Albano, Laetitia; Viklický, Ondrej; Merville, Pierre; Tydén, Gunnar; Mourad, Michel; Lõhmus, Aleksander; Witzke, Oliver; Christiaans, Maarten H L; Brown, Malcolm W; Undre, Nasrullah; Kazeem, Gbenga; Kuypers, Dirk R J

    2017-08-01

    ADVANCE (NCT01304836) was a phase 4, multicenter, prospectively randomized, open-label, 24-week study comparing the incidence of posttransplantation diabetes mellitus (PTDM) with 2 prolonged-release tacrolimus corticosteroid minimization regimens. All patients received prolonged-release tacrolimus, basiliximab, mycophenolate mofetil and 1 bolus of intraoperative corticosteroids (0-1000 mg) as per center policy. Patients in arm 1 received tapered corticosteroids, stopped after day 10, whereas patients in arm 2 received no steroids after the intraoperative bolus. The primary efficacy variable was the diagnosis of PTDM as per American Diabetes Association criteria (2010) at any point up to 24 weeks postkidney transplantation. Secondary efficacy variables included incidence of composite efficacy failure (graft loss, biopsy-proven acute rejection or severe graft dysfunction: estimated glomerular filtration rate (Modification of Diet in Renal Disease-4) <30 mL/min per 1.73 m), acute rejection and graft and patient survival. The full-analysis set included 1081 patients (arm 1: n = 528, arm 2: n = 553). Baseline characteristics and mean tacrolimus trough levels were comparable between arms. Week 24 Kaplan-Meier estimates of PTDM were similar for arm 1 versus arm 2 (17.4% vs 16.6%; P = 0.579). Incidence of composite efficacy failure, graft and patient survival, and mean estimated glomerular filtration rate were also comparable between arms. Biopsy-proven acute rejection and acute rejection were significantly higher in arm 2 versus arm 1 (13.6% vs 8.7%, P = 0.006 and 25.9% vs 18.2%, P = 0.001, respectively). Tolerability profiles were comparable between arms. A prolonged-release tacrolimus, basiliximab, and mycophenolate mofetil immunosuppressive regimen is efficacious, with a low incidence of PTDM and a manageable tolerability profile over 24 weeks of treatment. A lower incidence of biopsy-proven acute rejection was seen in patients receiving corticosteroids tapered over 10

  13. Liver transplantation in Greek children: 15 years experience

    Directory of Open Access Journals (Sweden)

    Dimitrios Takoudas

    2010-09-01

    Full Text Available Liver transplantation (LT is the only available live-saving procedure for children with irreversible liver failure. This paper reports our experience from the follow-up of 16 Greek children with end-stage liver failure who underwent a LT. Over a period of 15 years, 16 pediatric liver recipients received follow up after being subjected to OLT (orthotopic liver transplantation due to end-stage liver failure. Nine children initially presented with extrahepatic biliary atresia, 2 with acute liver failure after toxic mushroom ingestion, 2 with intrahepatic cholestasis, 2 with metabolic diseases and one with hepatoblastoma. Ten children received a liver transplant in the Organ Transplantation Unit of Aristotle University of Thessaloniki and the rest in other transplant centers. Three transplants came from a living-related donor and 13 from a deceased donor. Six children underwent immunosuppressive treatment with cyclo­sporine, mycophenolate mofetil and corticosteroids, and 7 with tacrolimus, mycophenolate mofetil and corticosteroids. Three out of 16 children died within the first month after the transplantation due to post-transplant complications. Three children presented with acute rejection and one with chronic organ rejection which was successfully managed. Five children presented with cytomegalovirus infection, 5 with Epstein-Barr virus, 2 with HSV1,2, 2 with ParvoB19 virus, 2 with varicella-zoster virus and one with C. Albicans infection. One child presented with upper gastrointestinal hemorrhage and one with small biliary paucity. A satisfying outcome was achieved in most cases, with good graft function, except for the patient with small biliary paucity who required re-transplantation. The long-term clinical course of liver transplanted children is good under the condition that they are attended in specialized centers.

  14. One year results of preoperative single bolus ATG-Fresenius induction therapy in sensitized renal transplant recipients.

    Science.gov (United States)

    Wang, D; Chen, J H; Wu, W Z; Yang, S L; Wu, G J; Wang, H; Tan, J M

    2007-01-01

    Sensitization in kidney transplantation is associated with more acute rejections, inferior graft survival, and an increase in delayed graft function. This study was designed to evaluate the efficacy and safety of preoperative single bolus antithymocyte globulin (ATG) induction therapy in sensitized renal transplant recipients. Fifty-six cadaveric donor kidney transplant recipients were divided into two groups: Group I (nonsensitized group, n = 30) and group II (sensitized group, PRA>10%, n = 26). ATG was given as a single preoperative bolus induction therapy to group II (ATG IV; 9 mg/kg). The group I patients were treated with mycophenolate mofetil preoperatively as induction therapy. The basic immunosuppressive regimen included tacrolimus (FK-506) or cyclosporine, mycophenolate mofetil, and prednisolone. After hospital discharge, patients were followed on a routine outpatient basis for 12 months. Acute rejection episodes (ARE) occurred in 20% (6/30) of group I and 15.38% (4/26) of group II patients (P = NS). Infections occurred in eight patients (26.7%) as 11 episodes (36.7%), averaging 1.4 episodes per infected patient in group 1, and 6 patients (23.1%) for a total of 10 episodes (38.5%), averaging 1.7 episodes per infected patient, in group II (P = NS). Occurrence of side effects and hospital stay were almost comparable in the two groups. No delayed graft function was observed in either group. The 12-month actuarial patient and graft survival were 100% in Group I and II. A preoperative single bolus ATG induction therapy was an effective and safe therapeutic measure, yielding an acceptable acute rejection rate in presensitized renal transplant recipients.

  15. Impact of maintenance immunosuppressive therapy on the fecal microbiome of renal transplant recipients: Comparison between an everolimus- and a standard tacrolimus-based regimen.

    Directory of Open Access Journals (Sweden)

    Gianluigi Zaza

    Full Text Available The gut microbiome is the full set of microbes living in the gastrointestinal tract and is emerging as an important dynamic/fluid system that, if altered by environmental, dietetic or pharmacological factors, could considerably influence drug response. However, the immunosuppressive drug-induced modifications of this system are still poorly defined.We employed an innovative bioinformatics approach to assess differences in the whole-gut microbial metagenomic profile of 20 renal transplant recipients undergoing maintenance treatment with two different immunosuppressive protocols. Nine patients were treated with everolimus plus mycophenolate mofetil (EVE+MMF group, and 11 patients were treated with a standard therapy with tacrolimus plus mycophenolate mofetil (TAC+MMF group.A statistical analysis of comparative high-throughput data demonstrated that although similar according to the degree of Shannon diversity (alpha diversity at the taxonomic level, three functional genes clearly discriminated EVE+MMF versus TAC+MMF (cutoff: log2 fold change≥1, FDR≤0.05. Flagellar motor switch protein (fliNY and type IV pilus assembly protein pilM (pilM were significantly enriched in TAC+MMF-treated patients, while macrolide transport system mrsA (msrA was more abundant in patients treated with EVE+MMF. Finally, PERMANOVA revealed that among the variables analyzed and included in our model, only the consumption of sugar significantly influenced beta diversity.Our study, although performed on a relatively small number of patients, showed, for the first time, specific immunosuppressive-related effects on fecal microbiome of renal transplant recipients and it suggested that the analysis of the gut microbes community could represent a new tool to better understand the effects of drugs currently employed in organ transplantations. However, multicenter studies including healthy controls should be undertaken to better address this objective.

  16. Impact of maintenance immunosuppressive therapy on the fecal microbiome of renal transplant recipients: Comparison between an everolimus- and a standard tacrolimus-based regimen.

    Science.gov (United States)

    Zaza, Gianluigi; Dalla Gassa, Alessandra; Felis, Giovanna; Granata, Simona; Torriani, Sandra; Lupo, Antonio

    2017-01-01

    The gut microbiome is the full set of microbes living in the gastrointestinal tract and is emerging as an important dynamic/fluid system that, if altered by environmental, dietetic or pharmacological factors, could considerably influence drug response. However, the immunosuppressive drug-induced modifications of this system are still poorly defined. We employed an innovative bioinformatics approach to assess differences in the whole-gut microbial metagenomic profile of 20 renal transplant recipients undergoing maintenance treatment with two different immunosuppressive protocols. Nine patients were treated with everolimus plus mycophenolate mofetil (EVE+MMF group), and 11 patients were treated with a standard therapy with tacrolimus plus mycophenolate mofetil (TAC+MMF group). A statistical analysis of comparative high-throughput data demonstrated that although similar according to the degree of Shannon diversity (alpha diversity) at the taxonomic level, three functional genes clearly discriminated EVE+MMF versus TAC+MMF (cutoff: log2 fold change≥1, FDR≤0.05). Flagellar motor switch protein (fliNY) and type IV pilus assembly protein pilM (pilM) were significantly enriched in TAC+MMF-treated patients, while macrolide transport system mrsA (msrA) was more abundant in patients treated with EVE+MMF. Finally, PERMANOVA revealed that among the variables analyzed and included in our model, only the consumption of sugar significantly influenced beta diversity. Our study, although performed on a relatively small number of patients, showed, for the first time, specific immunosuppressive-related effects on fecal microbiome of renal transplant recipients and it suggested that the analysis of the gut microbes community could represent a new tool to better understand the effects of drugs currently employed in organ transplantations. However, multicenter studies including healthy controls should be undertaken to better address this objective.

  17. Impact of maintenance immunosuppressive therapy on the fecal microbiome of renal transplant recipients: Comparison between an everolimus- and a standard tacrolimus-based regimen

    Science.gov (United States)

    Dalla Gassa, Alessandra; Felis, Giovanna; Granata, Simona; Torriani, Sandra; Lupo, Antonio

    2017-01-01

    Background The gut microbiome is the full set of microbes living in the gastrointestinal tract and is emerging as an important dynamic/fluid system that, if altered by environmental, dietetic or pharmacological factors, could considerably influence drug response. However, the immunosuppressive drug-induced modifications of this system are still poorly defined. Methods We employed an innovative bioinformatics approach to assess differences in the whole-gut microbial metagenomic profile of 20 renal transplant recipients undergoing maintenance treatment with two different immunosuppressive protocols. Nine patients were treated with everolimus plus mycophenolate mofetil (EVE+MMF group), and 11 patients were treated with a standard therapy with tacrolimus plus mycophenolate mofetil (TAC+MMF group). Results A statistical analysis of comparative high-throughput data demonstrated that although similar according to the degree of Shannon diversity (alpha diversity) at the taxonomic level, three functional genes clearly discriminated EVE+MMF versus TAC+MMF (cutoff: log2 fold change≥1, FDR≤0.05). Flagellar motor switch protein (fliNY) and type IV pilus assembly protein pilM (pilM) were significantly enriched in TAC+MMF-treated patients, while macrolide transport system mrsA (msrA) was more abundant in patients treated with EVE+MMF. Finally, PERMANOVA revealed that among the variables analyzed and included in our model, only the consumption of sugar significantly influenced beta diversity. Conclusions Our study, although performed on a relatively small number of patients, showed, for the first time, specific immunosuppressive-related effects on fecal microbiome of renal transplant recipients and it suggested that the analysis of the gut microbes community could represent a new tool to better understand the effects of drugs currently employed in organ transplantations. However, multicenter studies including healthy controls should be undertaken to better address this

  18. Assessment of tissue fibrosis in skin biopsies from patients with systemic sclerosis employing confocal laser scanning microscopy: an objective outcome measure for clinical trials?

    Science.gov (United States)

    Busquets, Joanna; Del Galdo, Francesco; Kissin, Eugene Y.

    2010-01-01

    Objectives. To obtain an objective, unbiased assessment of skin fibrosis in patients with SSc for use in clinical trials of SSc disease-modifying therapeutics. Methods. Skin biopsies from the dorsal forearm of six patients with diffuse SSc and six healthy controls, and skin biopsies from the forearm of one patient with diffuse SSc before and following 1 year treatment with mycophenolate mofetil were analysed by confocal laser scanning microscopy (CLSM) with specific antibodies against collagen types I and III or fibronectin. The integrated density of fluorescence (IDF) was calculated employing National Institutes of Health-ImageJ software in at least four different fields per biopsy spanning the full dermal thickness. Results. The intensities of collagen types I and III and fibronectin IDF were 174, 147 and 139% higher in SSc skin than in normal skin, respectively. All differences were statistically significant. The sum of the IDF values obtained for the three proteins yielded a comprehensive fibrosis score. The average fibrosis score for the six SSc samples was 28.3 × 106 compared with 18.6 × 106 for the six normal skin samples (P < 0.0001). Comparison of skin biopsies obtained from the same SSc patient before treatment and after 12 months of treatment with mycophenolate mofetil showed a reduction of 39% in total fibrosis score after treatment. Conclusions. CLSM followed by quantitative image analysis provides an objective and unbiased assessment of skin fibrosis in SSc and could be a useful end-point for clinical trials with disease-modifying agents to monitor the response or progression of the disease. PMID:20202926

  19. Treatment outcomes for patients with Middle Eastern Respiratory Syndrome Coronavirus (MERS CoV) infection at a coronavirus referral center in the Kingdom of Saudi Arabia.

    Science.gov (United States)

    Al Ghamdi, Mohammed; Alghamdi, Khalid M; Ghandoora, Yasmeen; Alzahrani, Ameera; Salah, Fatmah; Alsulami, Abdulmoatani; Bawayan, Mayada F; Vaidya, Dhananjay; Perl, Trish M; Sood, Geeta

    2016-04-21

    Middle Eastern Respiratory Syndrome coronavirus (MERS-CoV) is a poorly understood disease with no known treatments. We describe the clinical features and treatment outcomes of patients with laboratory confirmed MERS-CoV at a regional referral center in the Kingdom of Saudi Arabia. In 2014, a retrospective chart review was performed on patients with a laboratory confirmed diagnosis of MERS-CoV to determine clinical and treatment characteristics associated with death. Confounding was evaluated and a multivariate logistic regression was performed to assess the independent effect of treatments administered. Fifty-one patients had an overall mortality of 37 %. Most patients were male (78 %) with a mean age of 54 years. Almost a quarter of the patients were healthcare workers (23.5 %) and 41 % had a known exposure to another person with MERS-CoV. Survival was associated with male gender, working as a healthcare worker, history of hypertension, vomiting on admission, elevated respiratory rate, abnormal lung exam, elevated alanine transaminase (ALT), clearance of MERS-CoV on repeat PCR polymerase chain reaction (PCR) testing, and mycophenolate mofetil treatment. Survival was reduced in the presence of coronary artery disease, hypotension, hypoxemia, CXR (chest X-ray) abnormalities, leukocytosis, creatinine >1 · 5 mg/dL, thrombocytopenia, anemia, and renal failure. In a multivariate analysis of treatments administered, severity of illness was the greatest predictor of reduced survival. Care for patients with MERS-CoV remains a challenge. In this retrospective cohort, interferon beta and mycophenolate mofetil treatment were predictors of increased survival in the univariate analysis. Severity of illness was the greatest predictor of reduced survival in the multivariate analysis. Larger randomized trials are needed to better evaluate the efficacy of these treatment regimens for MERS-CoV.

  20. The importance of assessing medication exposure to the definition of refractory disease in systemic lupus erythematosus.

    Science.gov (United States)

    Arnaud, Laurent; Zahr, Noël; Costedoat-Chalumeau, Nathalie; Amoura, Zahir

    2011-09-01

    Treatment of patients with Systemic Lupus Erythematosus (SLE) who have active disease refractory to current therapeutic strategies continues to be a real challenge. Here, we propose that the classic definition of refractory SLE patients - failure to achieve adequate response to the standard of care - should be further refined to incorporate the dimension of adequate drug exposure. Inter-individual pharmacokinetic variability may induce insufficient exposure to many drugs used in SLE, leading to both apparent inefficacy of treatments and inappropriate therapeutic escalation. Among others, we have shown that individual assessment of exposure to mycophenolic acid, the active metabolite of mycophenolate mofetil (MMF) could be used to determine whether a given patient received adequate doses of MMF. We have also shown that measuring blood concentrations of hydroxychloroquine could be used as an efficient way to assess observance, which is a critical issue since a significant proportion of refractory SLE patients is likely to have poor observance as the primary source of treatment failure. Finally, we have underlined the importance of assessing drug interactions as SLE patients often require, in addition to immunosuppressants, several other drugs to prevent or treat associated conditions, which may result in decreased exposure to immunosuppressants. Considering these data, we believe that refractory SLE patients should not only be defined as the failure to achieve adequate therapeutic response to the standard of care, but should also incorporate the dimension of inadequate pharmacokinetic exposure and include drug blood level, interaction and observance monitoring. Copyright © 2011. Published by Elsevier B.V.

  1. Generic maintenance immunosuppression in solid organ transplant recipients.

    Science.gov (United States)

    Ensor, Christopher R; Trofe-Clark, Jennifer; Gabardi, Steven; McDevitt-Potter, Lisa M; Shullo, Michael A

    2011-11-01

    Survival after solid organ transplantation has increased in the era of tacrolimus and mycophenolate. This increased survival could be due in part to the broad clinical use of these potent and specific agents for maintenance immunosuppression. These drugs have enhanced specificity and potency for T and B lymphocytes compared with their predecessors, cyclosporine and azathioprine. Between 2008 and 2010, the United States Food and Drug Administration approved several generic formulations of both tacrolimus and mycophenolate mofetil. Deciding whether generic products can be safely substituted for the innovator product is a clinical dilemma similar to that which occurred when generic formulations of cyclosporine became available. We describe the concerns regarding generic immunosuppression use, summarize expert opinion and consensus statements in transplantation, analyze the potential impact of generic substitution, and provide estimates of populations affected based on generic drug market penetration. Formulary considerations such as cost, availability, and potential drug ordering and drug selection errors are described, and transplant coordinator and patient perspectives are reviewed. Finally, general recommendations about the use of generic maintenance immunosuppression in solid organ transplant recipients are provided. Although more research is needed to confirm clinical and therapeutic equivalence and pharmacoeconomic benefit, generic immunosuppressants can be safely substituted for innovator products as long as patients consistently receive the same product, patients and clinicians are aware of when substitutions occur, and enhanced therapeutic drug monitoring is provided during the transition.

  2. Anticancer drugs in Portuguese surface waters - Estimation of concentrations and identification of potentially priority drugs.

    Science.gov (United States)

    Santos, Mónica S F; Franquet-Griell, Helena; Lacorte, Silvia; Madeira, Luis M; Alves, Arminda

    2017-10-01

    Anticancer drugs, used in chemotherapy, have emerged as new water contaminants due to their increasing consumption trends and poor elimination efficiency in conventional water treatment processes. As a result, anticancer drugs have been reported in surface and even drinking waters, posing the environment and human health at risk. However, the occurrence and distribution of anticancer drugs depend on the area studied and the hydrological dynamics, which determine the risk towards the environment. The main objective of the present study was to evaluate the risk of anticancer drugs in Portugal. This work includes an extensive analysis of the consumption trends of 171 anticancer drugs, sold or dispensed in Portugal between 2007 and 2015. The consumption data was processed aiming at the estimation of predicted environmental loads of anticancer drugs and 11 compounds were identified as potentially priority drugs based on an exposure-based approach (PEC b > 10 ng L -1 and/or PEC c > 1 ng L -1 ). In a national perspective, mycophenolic acid and mycophenolate mofetil are suspected to pose high risk to aquatic biota. Moderate and low risk was also associated to cyclophosphamide and bicalutamide exposition, respectively. Although no evidences of risk exist yet for the other anticancer drugs, concerns may be associated with long term effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. August 2015 critical care case of the month: a diagnostic branch of medicine

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    Love WT

    2015-08-01

    Full Text Available No abstract available. Article truncated after 150 words. History of Present Illness: A 66-year-old man had undergone an orthotopic heart transplantation on March 28th, 2015 due to end-stage cardiomyopathy. During a recent hospitalization from 6/26-7/2 a transbronchial lung biopsy was suggestive of subacute rejection. He was treated with: Plasmapheresis x 3; Intravenous immunoglobulin (IVIG; 500 mg Solu-Medrol daily; Tacrolimus held as supra-therapeutic level of 16.2; Mycophenolate decreased to 500mg BID; Prednisone at 10mg BID on discharge. On July 3rd he began having cough productive of clear sputum, nausea, vomiting, and headache. Subsequently he had body aches, subjective fever, chills, night sweats, and a poor appetite with a 4 kg weight loss over the last week. There was also a history of several falls after “losing his balance". Past Medical History: There was also a history of type 2 diabetes mellitus, chronic kidney disease, coronary artery disease with coronary artery bypass grafting in 2000. Physical Examination: Vital signs: T-37.1 ...

  4. Clinical Risk Scoring Models for Prediction of Acute Kidney Injury after Living Donor Liver Transplantation: A Retrospective Observational Study.

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    Mi Hye Park

    Full Text Available Acute kidney injury (AKI is a frequent complication of liver transplantation and is associated with increased mortality. We identified the incidence and modifiable risk factors for AKI after living-donor liver transplantation (LDLT and constructed risk scoring models for AKI prediction. We retrospectively reviewed 538 cases of LDLT. Multivariate logistic regression analysis was used to evaluate risk factors for the prediction of AKI as defined by the RIFLE criteria (RIFLE = risk, injury, failure, loss, end stage. Three risk scoring models were developed in the retrospective cohort by including all variables that were significant in univariate analysis, or variables that were significant in multivariate analysis by backward or forward stepwise variable selection. The risk models were validated by way of cross-validation. The incidence of AKI was 27.3% (147/538 and 6.3% (34/538 required postoperative renal replacement therapy. Independent risk factors for AKI by multivariate analysis of forward stepwise variable selection included: body-mass index >27.5 kg/m2 [odds ratio (OR 2.46, 95% confidence interval (CI 1.32-4.55], serum albumin 20 (OR 2.01, 95%CI 1.17-3.44, operation time >600 min (OR 1.81, 95%CI 1.07-3.06, warm ischemic time >40 min (OR 2.61, 95%CI 1.55-4.38, postreperfusion syndrome (OR 2.96, 95%CI 1.55-4.38, mean blood glucose during the day of surgery >150 mg/dl (OR 1.66, 95%CI 1.01-2.70, cryoprecipitate > 6 units (OR 4.96, 95%CI 2.84-8.64, blood loss/body weight >60 ml/kg (OR 4.05, 95%CI 2.28-7.21, and calcineurin inhibitor use without combined mycophenolate mofetil (OR 1.87, 95%CI 1.14-3.06. Our risk models performed better than did a previously reported score by Utsumi et al. in our study cohort. Doses of calcineurin inhibitor should be reduced by combined use of mycophenolate mofetil to decrease postoperative AKI. Prospective randomized trials are required to address whether artificial modification of hypoalbuminemia, hyperglycemia

  5. Effects of immunosuppressive treatment on protein expression in rat kidney

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    Kędzierska K

    2014-09-01

    were observed between the group receiving cyclosporine, mycophenolate mofetil, and glucocorticoids (CMG and the control group. In contrast, compared to the control group, animals receiving tacrolimus, mycophenolate mofetil, and glucocorticoids (TMG exhibited higher expression of proteins responsible for renal drug metabolism and lower expression levels of cytoplasmic actin and the major urinary protein. In the TMG group, we observed higher expression of proteins responsible for drug metabolism and a decrease in the expression of respiratory chain enzymes (thioredoxin-2 and markers of distal renal tubular damage (heart fatty acid-binding protein compared to expression in the CMG group. The consequences of the reported changes in protein expression require further study. Keywords: Proteomics, drug effects, immunosuppression, rats

  6. How large are the differences between originator and generic prices? Analysis of five molecules in 16 European countries

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    Sabine Vogler

    2012-12-01

    Full Text Available OBJECTIVE: To survey the price differences between originators and generics for a selected basket of molecules and to analyze similarities and differences with regard to the countries included and their generic policies. METHODS: Ex-factory prices as of November 2011 of five molecules provided from the Pharma Price Information (PPI service of the Austrian Health Institute were analyzed for 16 European countries (Austria, Belgium, Denmark, Finland, France, Germany, Greece, Ireland, Italy, the Netherlands, Norway, Portugal, Spain, Switzerland, Sweden, UK. The selected molecules were gemcitabine, mycophenolate mofetil, olanzapine, risperidone and sumatriptan. For a specific presentation (same pack size, dosage and pharmaceutical form of each molecule, the prices of the original product and the “most common generic” as defined by PPI were compared. RESULTS: Considerable variations among the extent of price differences between originator and generic were identified (gemicitabine: lowest price difference of 1.4% between originator and generic in Belgium and highest difference of 73.4% in Portugal; mycophenolate mofetil: 3.4% Norway – 71.7% Netherlands; olanzapine: 0.1% Spain – 97.1% Sweden; risperidone: 0.9% Netherlands – 97.3% UK; sumatriptan: 5.8% Greece – 95.0% Denmark. Further, no difference at all between originator and generic prices was found for some molecules in a few countries (Norway: for 4 of the 5 molecules analyzed; Spain: 3; Belgium: 2; in Austria, France and Greece for one molecule respectively. For the five molecules of the sample, Greece, Spain, Ireland and Norway consistently displayed lower price differences whereas Denmark, Finland and Sweden tended to show higher differences between originator and generic prices. CONCLUSION: Even if this research is illustrative and not representative due to the small sample size, results suggest confirming large differences across Europe. It appears that countries (e.g. Denmark

  7. Immunosupressive therapy in children with steroid-resistant nephrotic syndrome: single center experience.

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    Echeverri, Catalina Velez; Valencia, Gustavo Adolfo Zuluaga; Higuita, Lina Maria Serna; Gayubo, Ana Katherina Serrano; Ochoa, Carolina Lucia; Rosas, Luisa Fernanda Rojas; Muñoz, Laura Carolina; Sierra, Javier; Zuleta, Jhon Jairo; Ruiz, Juan José Vanegas

    2013-01-01

    [corrected] Nephrotic syndrome is one of the most frequent glomerular diseases among children, and steroid therapy remains as the treatment choice. In spite of this, 10 to 15% of the patients are steroidresistant, and the best therapy for such cases has never been defined. Mycophenolate acid (MA) is one of the treatments used in such situations. To describe the clinical behavior of children diagnosed with steroid-resistant nephrotic syndrome (SRNS) and to assess the therapeutic response to MA. This was a retrospective and descriptive study. 26 clinical records of patients with SRNS; 70% male and 30% female. All patients underwent kidney biopsies, which showed a predominance of focal segmental glomerulosclerosis (FSGS). The immunosuppresive drugs used were: Mycophenolate mofetil (MMF) 100%, Cyclosporine 69.2%, Cyclophosphamide 23.1%, and Rituximab 23%. One month after treatment initiation with MMF 61.5% achieved remission. The median of relapses per year for the patients was 3 (p25: 2.75 - p75: 4). This median became 1 (p25: 1 - p75: 3.25) after using this medication (p = 0.08). Furthermore, prior to the start of the MMF treatment, the median of the steroid dose was 1 (p25: 0.5- p75: 1.62) mg/k/day. After using MMF, this median became 0.07 (p25: 0 - p75: 0.55) mg/k/day (p < 0.001), in 8 patients prednisolone was stopped. In our experience, treatment with MMF showed positive results such as decrease in the frequency of relapses, less proteinuria, and reduction in the dose of steroids administered without deterioration of glomerular filtration rates. However, more studies are needed to assess efficacy, safety, and optimal dosage.

  8. Immunosupressive therapy in children with steroid-resistant nephrotic syndrome: single center experience

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    Catalina Velez Echeverri

    2013-09-01

    Full Text Available INTODUCTION: Nephrotic syndrome is one of the most frequent glomerular diseases among children, and steroid therapy remains as the treatment choice. In spite of this, 10 to 15% of the patients are steroidresistant, and the best therapy for such cases has never been defined. Mycophenolate acid (MA is one of the treatments used in such situations. OBJECTIVE: To describe the clinical behavior of children diagnosed with steroid-resistant nephrotic syndrome (SRNS and to assess the therapeutic response to MA. METHODS: This was a retrospective and descriptive study. RESULTS: 26 clinical records of patients with SRNS; 70% male and 30% female. All patients underwent kidney biopsies, which showed a predominance of focal segmental glomerulosclerosis (FSGS. The immunosuppresive drugs used were: Mycophenolate mofetil (MMF 100%, Cyclosporine 69.2%, Cyclophosphamide 23.1%, and Rituximab 23%. One month after treatment initiation with MMF 61.5% achieved remission. The median of relapses per year for the patients was 3 (p25: 2.75 - p75: 4. This median became 1 (p25: 1 - p75: 3.25 after using this medication (p = 0.08. Furthermore, prior to the start of the MMF treatment, the median of the steroid dose was 1 (p25: 0.5- p75: 1.62 mg/k/day. After using MMF, this median became 0.07 (p25: 0 - p75: 0.55 mg/k/day (p < 0.001, in 8 patients prednisolone was stopped. CONCLUSION: In our experience, treatment with MMF showed positive results such as decrease in the frequency of relapses, less proteinuria, and reduction in the dose of steroids administered without deterioration of glomerular filtration rates. However, more studies are needed to assess efficacy, safety, and optimal dosage.

  9. Adverse Event Burden, Resource Use, and Costs Associated with Immunosuppressant Medications for the Treatment of Systemic Lupus Erythematosus: A Systematic Literature Review

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    A. Oglesby

    2013-01-01

    Full Text Available This paper assessed the burden of adverse events (AEs associated with azathioprine (AZA, cyclophosphamide (CYC, mycophenolate mofetil (MMF, methotrexate (MTX, and cyclosporine (CsA in patients with systemic lupus erythematosus (SLE. Thirty-eight publications were included. Incidence of AEs ranged from 42.8% to 97.3%. Common AEs included infections (2.4–77%, gastrointestinal AEs (3.2–66.7%, and amenorrhea and/or ovarian complications (0–71%. More hematological cytopenias were associated with AZA (14 episodes than MMF (2 episodes. CYC was associated with more infections than MMF (40–77% versus 12.5–32%, resp. or AZA (17–77% versus 11–29%, resp.. Rates of hospitalized infections were similar between MMF and AZA patients, but higher for those taking CYC. There were more gynecological toxicities with CYC than MMF (32–36% versus 3.6–6%, resp. or AZA (32–71% versus 8–18%, resp.. Discontinuation rates due to AEs were 0–44.4% across these medications. In summary, the incidence of AEs associated with SLE immunosuppressants was consistently high as reported in the literature; discontinuations due to these AEs were similar across treatments. Studies on the economic impact of these AEs were sparse and warrant further study. This paper highlights the need for more treatment options with better safety profiles.

  10. Defecation of a colon cast as a rare presentation of acute graft-versus-host disease

    International Nuclear Information System (INIS)

    Al Ashgar, Hamad; Peedikayil, Musthafa; Chaudhri, Naeem; AlGhamdi, Abdulmonem

    2009-01-01

    Diffuse involvement of the gastrointestinal tract by graft versus host disease (GVHD) is a common complication of allogeneic hematopoietic stem cell transplant (HSCT). Gastrointestinal GVHD usually presents 3 or more weeks after HSCT and is characterized by profuse diarrhea, anorexia, nausea, vomiting, abdominal pain and gastrointestinal bleeding. We report a case of a 23 year old male who had undergone allogeneic HSCT and presented with bloody diarrhea on the 90th day post-HSCT. On the fourth day of admission, the patient passed per rectum a 27-cm long pinkish colored fleshy material recognized as a colon cast. Sigmoidoscopy showed a congested and erythematous rectum with the remaining portion of the colon cast attached to the proximal part of the sigmoid colon. A biopsy from the rectal wall was suggestive of grade 4 GVHD. The patient was treated with methylprednisolone, cyclosporine and mycophenolate mofetil, with a partial response (diarrhea and abdominal pain improved), but then he developed multiple other medical complications and died after 3 months. (author)

  11. Late acute antibody mediated rejection after nine years of renal transplantation

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    Halim Medhat

    2010-01-01

    Full Text Available Acute Antibody Mediated Rejection (AMR is rarely reported as a long-term com-plication of renal transplantation, and it can present on top of another chronic pathology affecting the graft. A 45-year-old gentleman with chronic kidney disease due to unknown etiology received renal transplantation from his sister with 4 HLA mismatches. He received antithymocte globulin induction therapy and was maintained on steroids, azathioprine (AZA and cyclosporine A (CsA. Up to eight years post-transplantation he was clinically and biochemically stable. He lost follow-up for about one year, and then presented with nephritic nephrotic syndrome and rise of serum creatinine (SCr. to 210 μmol/L. Graft biopsy revealed picture suggestive of acute AMR on top of de novo membranoprolipherative glomerulonephritis (MPGN with focal crescent formation, diffuse immune complex deposition and peri-tubular capillaries C4d positivity. Anti-HLA donor specific antibodies were highly positive for B and T cells class I and class II. The patient was treated with intravenous immunoglobulin, plasma exchange and anti-CD20 (rituximab. AZA was changed to mycophenolate mofetil and CsA to tacrolimus. He had partial response, but SCr. continued at 220 μmol/L.

  12. Treatment Strategies of Adult Primary Focal Segmental Glomerulosclerosis: A Systematic Review Focusing on the Last Two Decades

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    Arno Beer

    2016-01-01

    Full Text Available Adult primary focal segmental glomerulosclerosis (FSGS remains a therapeutic challenge for the treating physician. With the advent of novel immunosuppressive measures, our arsenal of therapeutic options increased considerably. The aim of this review was to summarize reports published over the last two decades which reported on treatment outcome. Most reports included patients with a steroid-resistant (SR disease course, yet the cohort with the highest unmet need, since persistent nephrotic range proteinuria is associated with a poor renal prognosis and portends a high risk of developing end-stage renal disease. While in first-line treatment, steroid treatment remains the recommended standard with an overall remission rate of 50% and higher, optimal treatment strategies for steroid-dependent/multirelapsing (SD/MR and SR patients have to be defined. In both entities, calcineurin inhibitors showed good efficacy, while mycophenolate mofetil was less effective in SR cases compared to those with SD/MR. The same was true for rituximab, a monoclonal antibody targeting B-cells. In resistant cases, addition of extracorporeal treatment options or treatment with alkylating agents may be considered. To shape the future for treatment of FSGS, international collaborations to conduct larger clinical trials are needed to identify potential novel efficacious immunosuppressive or immunomodulatory therapies.

  13. Pharmacologic strategies in the prevention and treatment of corneal transplant rejection.

    Science.gov (United States)

    Tabbara, Khalid F

    2008-06-01

    Corneal transplantation remains one of the most successful organ transplantation procedures in humans. The unique structure of the cornea, with its absence of blood vessels and corneal lymphatic, allows the survival of corneal allograft. Recent advances in sutures, storage media, microsurgical instrumentation, and new pharmacological strategies have greatly improved the success of corneal transplantation and the prevention of corneal allograft rejection. Our strategies in the management and prevention of corneal graft rejection can modify and improve the survival of corneal allografts. Preoperative evaluation, understanding the risk factors, and management of ocular surface disorders may greatly improve the survival of the corneal transplant. Early recognition of corneal allograft rejection and aggressive treatment may improve the survival of the corneal graft. Furthermore, patients who undergo corneal transplantation should be maintained under close ophthalmic surveillance and patients should be informed to report immediately whenever symptoms of corneal graft rejection occur. The mainstay of therapy is topical corticosteroids. In severe cases, periocular, intravenous, and oral corticosteroids therapy can be rendered. New therapeutic modalities such as cyclosporine, tacrolimus, daclizumab, mycophenolate mofetil, leflunomide, rapamycin, and others may prove to be of help in the prevention and treatment of corneal graft rejection. Early recognition of corneal graft rejection and prompt treatment are mandatory for the successful survival of the corneal allograft.

  14. Hypocomplementemic Urticarial Vasculitis Syndrome With Crescentic Glomerulonephritis.

    Science.gov (United States)

    Salim, Sohail Abdul; Yousuf, Tauqeer; Patel, Asha; Fülöp, Tibor; Agarwal, Mohit

    2018-02-01

    Hypocomplementemic urticarial vasculitis syndrome (HUVS) is a rare autoimmune disease characterized by multiple organ system involvement, including renal disease, with low complement levels. We report the case of a 31-year-old woman who presented with nonspecific symptoms including fatigue, diarrhea, macular rash and abdominal pain with acute renal failure leading to end-stage kidney disease. Laboratory results showed hematuria, nephrotic range proteinuria, worsening creatinine and low C1q levels. Left kidney biopsy showed proliferative glomerulonephritis with crescent formation. She was treated with 6 months of intravenous cyclophosphamide, followed by 2 doses of intravenous rituximab (1g each), thereafter maintained on mycophenolate mofetil and glucocorticoid-based therapy. She experienced a full recovery of renal function after 12 months of dialysis dependence. Hypocomplementemic urticarial vasculitis syndrome with crescentic glomerulonephritis is a rare disease with only 5 other reported cases in literature. In our case, we document a delayed but excellent renal recovery during a 2-year follow-up. Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  15. Long-Term Impact of Cyclosporin Reduction with MMF Treatment in Chronic Allograft Dysfunction: REFERENECE Study 3-Year Follow Up

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    L. Frimat

    2010-01-01

    Full Text Available Calcineurin inhibitor (CNI toxicity contributes to chronic allograft nephropathy (CAN. In the 2-year, randomized, study, we showed that 50% cyclosporin (CsA reduction in combination with mycophenolate mofetil (MMF treatment improves kidney function without increasing the risk for graft rejection/loss. To investigate the long-term effect of this regimen, we conducted a follow up study in 70 kidney transplant patients until 5 years after REFERENCE initiation. The improvement of kidney function was confirmed in the MMF group but not in the control group (CsA group. Four graft losses occurred, 2 in each group (graft survival in the MMF group 95.8% and 90.9% in control group. One death occurred in the control group. There was no statistically significant difference in the occurrence of serious adverse events or acute graft rejections. A limitation is the weak proportion of patient still remaining within the control group. On the other hand, REFERENCE focuses on the CsA regimen while opinions about the tacrolimus ones are still debated. In conclusion, CsA reduction in the presence of MMF treatment seems to maintain kidney function and is well tolerated in the long term.

  16. Diagnosis and therapy of autoimmune hepatitis.

    Science.gov (United States)

    Granito, Alessandro; Muratori, Paolo; Ferri, Silvia; Pappas, Georgios; Quarneti, Chiara; Lenzi, Marco; Bianchi, Francesco B; Muratori, Luigi

    2009-06-01

    Autoimmune hepatitis (AIH) is a chronic progressive hepatitis, characterized by interface hepatitis with lymphoplasmacellular infiltrates on liver biopsy, high serum globulin level and circulating autoantibodies. It is classified into two types, according to autoantibody profile: type 1 is characterized by anti-nuclear (ANA) and/or anti-smooth muscle (SMA) antibodies; type 2 by anti-liver kidney microsomal type 1 (anti-LKM-1) antibodies. AIH affects all ages, may be asymptomatic, frequently has an acute onset, and can present as fulminant hepatitis. The diagnosis of AIH is based on a scoring system codified by an international consensus. Corticosteroids alone or in conjunction with azathioprine is the treatment of choice in patients with AIH and results in remission induction in over 80% of patients. Alternative proposed strategies in patients who have failed to achieve remission on standard therapy or patients with drug toxicity include the use of cyclosporine, tacrolimus, budesonide or mycophenolate mofetil. Liver transplantation is the treatment of choice in managing decompensated disease, however AIH can recur or develop de novo after liver transplantation.

  17. Acute tubulointerstitial nephritis with severe renal impairment associated with multisystem IgG4-related disease

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    Rafael Coimbra Ferreira Beltrame

    Full Text Available Abstract The IgG4-related disease has a wide clinical spectrum where multiple organs can be affected, and the diagnosis depends on typical histopathological findings and an elevated IgG4 expression in plasma cells in the affected tissue. We describe the clinical presentation and evolution of a patient with acute tubulointerstitial nephritis, severe kidney failure and systemic manifestations such as lymphadenomegaly and chronic pancreatitis. The diagnosis was confirmed by the clinical picture and kidney and lymph node histopathology, in which immunohistochemistry of the lymphoid tissue showed policlonality and increased expression of IgG4, with a IgG4/total IgG ratio > 80%. The patient was treated with prednisone at a dose of 60 mg/day, followed by mycophenolate mofetil, and showed clinical and renal function improvement at 6 months of follow-up. The high index of suspicion of IgG4-related disease with multisystem involvement and the early treatment of this condition are essential to improve the prognosis of affected patients.

  18. Managing hypertriglyceridemia in children with systemic lupus erythematosus: Two sides of the same coin.

    Science.gov (United States)

    Basu, Biswanath; Babu, Binu George; Bhattacharyya, Suman

    Hypertriglyceridemia is common in children with systemic lupus erythematosus (SLE). A retrospective analysis of the baseline clinical-pathological presentation and treatment outcome (status of lipid profiles) was performed in two children with SLE, who presented with extreme hypertriglyceridemia over a follow-up period of four weeks. The children were treated with prednisolone, mycophenolate mofetil (MMF), hydroxychloroquine and hypolipidemic agents, depending on their disease status. On serial follow-up, the first child showed a significantly raised serum triglyceride level after receiving one week of oral prednisolone therapy. Anti-lipoprotein-lipase (LPL) autoantibody was absent. Lipid profile levels of this child gradually improved after replacing oral prednisolone with another immunosuppressant, namely MMF. The second child presented with extreme hypertriglyceridemia with positive anti-LPL autoantibody. She responded to plasmapheresis followed by increasing the dose of immunosuppressant. So, extreme hypertriglyceridemia in children with SLE may be steroid induced or due to presence of anti-LPL auto antibody. Management should be individualized depending on the etiology. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  19. Children with Steroid-resistant Nephrotic Syndrome: a Single-Center Study

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    Rahime Renda

    2016-01-01

    Full Text Available Background and Aim: Steroid-resistant nephrotic syndrome (SRNS accounts for 10%-20% of all cases of idiopathic nephrotic syndrome. These patients are at risk of developing end-stage renal disease. The aim of this study was to determine the demographic characteristics, renal biopsy findings, response to immunosuppressive treatment, and prognosis in pediatric patients with SRNS.Materials and Methods: This retrospective study included 31 patients diagnosed as primary SRNS. Age at first episode, gender, parental consanguinity, and familial history of nephrotic syndrome were recorded. Demographic characteristics, renal biopsy findings, response to immunosuppressive treatment, and prognosis were analyzed, as were the number of and treatment of relapses, extra-renal manifestations, and complications of disease and treatment.Results: Mean age at first episode of nephrotic syndrome was 4,1±2,9 years. At the end of the first immunosuppressive treatment cycle, 14 (51.8% patients achieved complete remission, 4 (14.8% patients achieved partial remission, and 9 patients (33.3% did not achieve remission. Analysis of the final status of the patients showed that 16 patients (51.6% developed remission, 5 patients (16% continued to have nephrotic range proteinuria and 10 patients (32% developed chronic renal failure (CRF.Conclusion: The treatment of SRNS remains controversial. Early genetic testing can help the inevitable immunosuppressive treatments which may not be effective and have several side effects. Calcineurin inhibitors and mycophenolate mofetil are known to be effective immunosuppressive drugs for treating steroid resistant nephrotic syndrome .

  20. Patient recruitment into a multicenter randomized clinical trial for kidney disease: report of the focal segmental glomerulosclerosis clinical trial (FSGS CT).

    Science.gov (United States)

    Ferris, Maria; Norwood, Victoria; Radeva, Milena; Gassman, Jennifer J; Al-Uzri, Amira; Askenazi, David; Matoo, Tej; Pinsk, Maury; Sharma, Amita; Smoyer, William; Stults, Jenna; Vyas, Shefali; Weiss, Robert; Gipson, Debbie; Kaskel, Frederick; Friedman, Aaron; Moxey-Mims, Marva; Trachtman, Howard

    2013-02-01

    We describe the experience of the focal segmental glomerulosclerosis clinical trial (FSGS CT) in the identification and recruitment of participants into the study. This National Institutes of Health funded study, a multicenter, open-label, randomized comparison of cyclosporine versus oral dexamethasone pulses plus mycophenolate mofetil, experienced difficulty and delays meeting enrollment goals. These problems occurred despite the support of patient advocacy groups and aggressive recruitment strategies. Multiple barriers were identified including: (1) inaccurate estimates of the number of potential incident FSGS patients at participating centers; (2) delays in securing one of the test agents; (3) prolonged time between IRB approval and execution of a subcontract (mean 7.5 ± 0.8 months); (4) prolonged time between IRB approval and enrollment of the first patient at participating sites (mean 19.6 ± 1.4 months); and (5) reorganization of clinical coordinating core infrastructure to align resources with enrollment. A Web-based anonymous survey of site investigators revealed site-related barriers to patient recruitment. The value of a variety of recruitment tools was of marginal utility in facilitating patient enrollment. We conclude that improvements in the logistics of study approval and regulatory start-up and testing of promising novel agents are important factors in promoting enrollment into randomized clinical trials in nephrology. © 2013 Wiley Periodicals, Inc.

  1. From Leflunomide to Teriflunomide: Drug Development and Immunosuppressive Oral Drugs in the Treatment of Multiple Sclerosis.

    Science.gov (United States)

    Aly, Lilian; Hemmer, Bernhard; Korn, Thomas

    2017-01-01

    Immunosuppressive drugs have been used in the treatment of multiple sclerosis (MS) for a long time. Today, orally available second generation immunosuppressive agents have been approved or are filed for licensing as MS therapeutics. Due to semi-selective targeting of cellular processes, these second-generation immunosuppressive compounds might rather be immunomodulatory. For example, Teriflunomide inhibits the de novo pyrimidine synthesis and thus only targets rapidly proliferating cells, including lymphocytes. It is used as first line disease modifying therapy (DMT) in relapsing-remitting MS (RRMS). Review of online content related to oral immunosuppressants in MS with an emphasis on Teriflunomide. Teriflunomide and Cladribine are second-generation immunosuppressants that are efficient in the treatment of MS patients. For Teriflunomide, a daily dose of 14 mg reduces the annualized relapse rate (ARR) by more than 30% and disability progression by 30% compared to placebo. Cladribine reduces the ARR by about 50% compared to placebo but has not yet been licensed due to unresolved safety concerns. We also discuss the significance of older immunosuppressive compounds including Azathioprine, Mycophenolate mofetile, and Cyclophosphamide in current MS therapy. Teriflunomide has shown a favorable safety and efficacy profile in RRMS and is a therapeutic option for a distinct group of adult patients with RRMS. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Sarcoidosis and uveitis.

    Science.gov (United States)

    Jamilloux, Yvan; Kodjikian, Laurent; Broussolle, Christiane; Sève, Pascal

    2014-08-01

    Uveitis is a frequent (20-50%) and early feature of sarcoidosis. Typical sarcoid uveitis presents with mutton-fat keratic precipitates, iris nodules, and anterior and posterior synechiae. Posterior involvement includes vitreitis, vasculitis, and choroidal lesions. Cystoid macular edema is the most important and sight-threatening consequence. Histologic proof from a biopsy is the gold standard for the diagnosis of ocular sarcoidosis. An international workshop has recently established diagnostic criteria for sarcoidosis uveitis when biopsy is unavailable or negative: these are based on a combination of ophthalmological findings and laboratory tests. The value of recent techniques, such as PET-scan and endoscopic ultrasound-guided, fine-needle aspiration of intrathoracic nodes needs to be assessed in future studies. Corticosteroids are the mainstay treatment for sarcoidosis. Systemic corticosteroids are indicated when uveitis does not respond to topical corticosteroids or when there is bilateral posterior involvement, especially macular edema and occlusive vasculitis. In up to 15% of cases, additional immunosuppression is used, including methotrexate, azathioprine, and mycophenolate mofetil. Infliximab and adalimumab have been recently proposed for the treatment of refractory or sight-threatening systemic sarcoidosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Research priorities in pediatric rheumatology: The Childhood Arthritis and Rheumatology Research Alliance (CARRA consensus

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    Mellins Elizabeth D

    2008-04-01

    Full Text Available Abstract Background North American pediatric rheumatologists have created an investigator-initiated research network (the Childhood Arthritis and Rheumatology Research Alliance – CARRA to facilitate multi-centre studies. One of the first projects undertaken by this network was to define, by consensus, research priorities for the group, and if possible a first group-sponsored clinical trial in which all members could participate. Methods We determined consensus using the Delphi approach. This approach has been used extensively in health research to reach consensus in large groups. It uses several successive iterations of surveys eliciting ideas and opinions from specialists in the field. Three surveys were designed based on this method and were distributed to members of CARRA to elicit and rank-order research priorities. Results A response rate of 87.6% was achieved in the final survey. The most highly ranked research suggestion was to study infliximab treatment of uveitis unresponsive to methotrexate. Other highly ranked suggestions were to study i the treatment of systemic arthritis with anakinra and ii the treatment of pediatric systemic lupus erythematosus with mycophenolate mofetil. Conclusion The Delphi approach was an effective and practical method to define research priorities in this group. Ongoing discussion and cooperation among pediatric rheumatologists in CARRA and others world-wide will help in developing further research priorities and to facilitate the execution of clinical trials in the future.

  4. Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis

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    İlknur Tuğal-Tutkun

    2016-04-01

    Full Text Available Pediatric uveitis may be a serious health problem because of the lifetime burden of vision loss due to severe complications if the problem is not adequately treated. Juvenile idiopathic arthritis (JIA-associated uveitis is characterized by insidious onset and potentially blinding chronic anterior uveitis. Periodic ophthalmologic screening is of utmost importance for early diagnosis of uveitis. Early diagnosis and proper immunomodulatory treatment are essential for good visual prognosis. The goal of treatment is to achieve enduring drug-free remission. The choice of therapeutic regimen needs to be tailored to each individual case. One must keep in mind that patients under immunomodulatory treatment should be monitored closely due to possible side effects. Local and systemic corticosteroids have long been the mainstay of therapy; however, long-term corticosteroid therapy should be avoided due to serious side effects. Steroid-sparing agents in the treatment of JIA-associated uveitis include antimetabolites and biologic agents in refractory cases. Among the various immunomodulatory agents, methotrexate is generally the first choice, as it has a well-established safety and efficacy profile in pediatric cases and does not appear to increase the risk of cancer. Other classic immunomodulators that may also be used in combination with methotrexate include azathioprine, mycophenolate mofetil, and cyclosporin A. Biologic agents, primarily tumor necrosis factor alpha inhibitors including infliximab or adalimumab, should be considered in cases of treatment failure with classic immunomodulatory agents.

  5. Emerging Drugs for Uveitis

    Science.gov (United States)

    Larson, Theresa; Nussenblatt, Robert B.; Sen, H. Nida

    2010-01-01

    Importance of the Field Uveitis is a challenging disease covering both infectious and noninfectious conditions. The current treatment strategies are hampered by the paucity of randomized controlled trials (RCTs) and few trials comparing efficacy of different agents. Areas Covered in this Review This review describes the current and future treatments of uveitis. A literature search was performed in PUBMED from 1965 to 2010 on drugs treating ocular inflammation with emphasis placed on more recent, larger studies. What the Reader Will Gain Readers should gain a basic understanding of current treatment strategies beginning with corticosteroids and transitioning to steroid sparing agents. Steroid sparing agents include the antimetabolites which include methotrexate, azathioprine, and mycophenolate mofetil; the calcineurin inhibitors which include cyclosporine, tacrolimus; alkylating agents which include cyclophosphamide and chlorambucil; and biologics which include the TNF-α inhibitors infliximab, adalimumab, and etanercept; daclizumab, interferon α2a, and rituximab. Take Home Message Newer agents are typically formulated from existing drugs or developed based on new advances in immunology. Future treatment will require a better understanding of the mechanisms involved in autoimmune diseases and better delivery systems in order to provide targeted treatment with minimal side effects. PMID:21210752

  6. TREATMENT APPROACH FOR JUVENILE IDIOPATHIC ARTHRITIS-RELATED UVEITIS: 2012 UPDATE

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    Francesco Zulian

    2012-01-01

    Full Text Available Chronic anterior uveitis is the most common extra-articular complication of juvenile idiopathic arthritis. It is more frequent in the early onset forms with a higher prevalence in the oligoarticular (40% than in other juvenile idiopathic arthritis subtypes (5–14%. The risk for severe visual impairment is still high due to the development of sight-threatening complications (synechiae, band keratopathy, cataract, glaucoma, cystoid macular oedema. Treatment is not standardized and requires a complex decision-making process, involving a close collaboration between paediatric ophthalmologist and rheumatologist. Topical therapy alone is often inadequate to control ocular inflammation and bulbar injections are too invasive to perform in children therefore immunosuppressive treatment is often advocated. Low dose methotrexate is the second-line agent mostly used although no controlled studies comparing effects of early to late methotrexate treatment have been reported. Mycophenolate mofetil is effective in controlling inflammation in methotrexate -refractory patients. Its efficacy, however, seems to be more relevant in intermediate or posterior uveitis, than in juvenile idiopathic arthritis uveitis and scleritis. Anti-TNFα agents, namely infliximab and adalimimab showed effectiveness in open-label studies but no wide controlled trials have been reported so far. Adalimimab is as effective as infliximab but has an easier way of administration and a better drug tolerance. Abatacept should be used in anti-TNF refractory patients with juvenile idiopathic arthritis uveitis.

  7. Intraocular inflammation in autoimmune diseases.

    Science.gov (United States)

    Pras, Eran; Neumann, Ron; Zandman-Goddard, Gisele; Levy, Yair; Assia, Ehud I; Shoenfeld, Yehuda; Langevitz, Pnina

    2004-12-01

    The uveal tract represents the vascular organ of the eye. In addition to providing most of the blood supply to the intraocular structures, it acts as a conduit for immune cells, particularly lymphocytes, to enter the eye. Consequently, the uveal tract is represented in many intraocular inflammatory processes. Uveitis is probably a misnomer unless antigens within the uvea are the direct targets of the inflammatory process. A better term of the condition is "intraocular inflammation" (IOI). To review the presence of IOI in autoimmune diseases, the immunopathogenic mechanisms leading to disease, and treatment. We reviewed the English medical literature by using MEDLINE (1984-2003) employing the terms "uveitis," "intraocular inflammation," and "autoimmune diseases." An underlying autoimmune disease was identified in up to 40% of patients with IOI, and included spondyloarthropathies, Behcets disease, sarcoidosis, juvenile chronic arthritis, Vogt-Koyanagi-Harada syndrome (an inflammatory syndrome including uveitis with dermatologic and neurologic manifestations), immune recovery syndrome, and uveitis with tubulointerstitial disease. The immunopathogenesis of IOI involves enhanced T-cell response. Recently, guidelines for the use of immunosuppressive drugs for inflammatory eye disease were established and include: corticosteroids, azathioprine, methotrexate, mycophenolate mofetil, cyclosporine, tacrolimus, cyclophosphamide, and chlorambucil. New therapies with limited experience include the tumor necrosis factor alpha inhibitors, interferon alfa, monoclonal antibodies against lymphocyte surface antigens, intravenous immunoglobulin (IVIG), and the intraocular delivery of immunosuppressive agents. An underlying autoimmune disease was identified in up to 40% of patients with IOI. Immunosuppressive drugs, biologic agents, and IVIG are employed for the treatment of IOI in autoimmune diseases.

  8. Anesthetic keratopathy presenting as bilateral Mooren-like ulcers

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    Khakshoor H

    2012-10-01

    Full Text Available Hamid Khakshoor,1 Majid Moshirfar,2 Rachel G Simpson,3 Hamid Gharaee,1 Amir H Vejdani,1 Steven M Christiansen,2 Jason N Edmonds,2 Nicholas L Behunin21Mashhad University of Medical Sciences, Department of Ophthalmology, Mashad, Iran; 2John A Moran Eye Center, University of Utah, Salt Lake City, UT, 3The University of Arizona College of Medicine, Phoenix, AZ, USAAbstract: This observational case report describes the development of bilateral Mooren-like ulcers in a patient with anesthetic keratopathy. A 42-year-old man with a recent history of minor eye trauma and pain self-treated with tetracaine eye drops presented with complaints of acutely worsening vision and severe pain bilaterally. His visual acuity at presentation was limited to hand motion. Slit-lamp examination revealed bilateral epithelial defects at the center of the cornea, and an area of stromal infiltration and thinning with an undermining leading edge resembling a Mooren's ulcer in both eyes. Corneal haze and hypopyon were visible. Anesthetic use was halted immediately and the patient was started on prednisolone and mycophenolate mofetil (Cellcept®, after which visual acuity gradually improved and pain decreased. Despite improvement of symptoms, residual epithelial defects remained, and the patient was ultimately treated with keratoplasty for recovery of vision. We suggest that anesthetic keratopathy should be included in the differential diagnosis for any patient presenting with ring-shaped stromal infiltrates or nonhealing epithelial defects.Keywords: anesthetic abuse, corneal damage, corneal ulceration

  9. Pediatric lupus nephritis presenting with terminal renal failure.

    Science.gov (United States)

    Besouw, Martine T P; Vande Walle, Johan G; Ilias, Mohamad I; Raes, Ann M; Prytula, Agnieszka A; Claeys, Lieve; Dehoorne, Jo L

    2016-12-01

    A 12-year-old Congolese girl presented with acute renal failure, edema, hypertension, hemoptysis, hematuria, and proteinuria after a history of throat infection. Renal ultrasound showed kidneys of normal size, with increased echogenicity of the cortical parenchyma and decreased corticomedullary differentiation. Other additional investigations showed pancytopenia with decreased complement (low C3 and C4). Antinuclear antibodies were strongly positive, including anti-double stranded DNA. Renal biopsy confirmed severe grade IV lupus nephritis. She was treated with high-dose steroids, mycophenolate mofetil and hydroxychloroquine, in addition to hemodialysis. After one week of intensive treatment, diuresis recovered and dialysis could be stopped after six sessions. We describe an uncommon case of severe lupus nephritis, presenting with terminal renal failure. Since the rarity of this disease presentation, other more common diagnoses have to be considered. Once the diagnosis of lupus nephritis is established, a choice has to be made between the different induction treatment protocols. The patient's ethnic background and other supportive therapies, such as the need for dialysis, can help to make this choice.

  10. ANCA-negative Churg-Strauss Syndrome

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    Syed Jamil Abdal

    2016-08-01

    Full Text Available A rare and a disease of unknown etiology, Churg-Strauss syndrome (CSS is a granulomatous necrotizing small vessel vasculitis characterized by the presence of asthma, sinusitis, and hypereosinophilia, which is initially described by Churg and Strauss in 1951. Because of its clinical and pathological features that overlap with those of the other anti-neutrophil antibody (ANCA-associated systemic vasculitides (AASVs and now the disease is classified as AASVs. The ANCA status may dictate the clinical phenotype. ANCA-positive patients are significantly more likely to have disease manifesta­tions associated with small-vessel vasculitis, including oecrotising glomemlonephritis, mononeuritis and purpura, whereas ANCA-negative cases predominantly likely to have cardiac and lung involvement. The objective of this case report is to point out the possibility of vasculitic rash in ANCA-negative CSS in a 35-year-old man and the disease rarely occurs in Bangladeshi population. We analyze the history, clinical examinations and relevant investigations related to the patient to establish the diagnosis in our department. The clinical scenario and biopsy help us to attain the diagnosis. But due to unavailability of patients' cohort we have limitations of comparison of ANCA status in Bangladeshi populations. Though ANCA-positive and ANCA-negative CSS differ phenotypically, primary therapy for both the conditions is systemic glucocorticoids. Additional immunosuppressive agents like cyclophosphamide, mycophenolate mofetil, azathioprine, rituxin1ab are occasionally added in patients with more advanced or refractory disease.

  11. Successful Pregnancies in Two Orthotopic Liver Transplant (OLT) Recipients in Iran; Two Case Reports.

    Science.gov (United States)

    Zahra, Tayebi; Seyyed Alireza, Taqhavi; Shirin, Shahbazi

    2009-10-01

    Pregnancy and parenting have been part of human life throughout history and liver transplant recipients are not any exception. This paper reports successful pregnancies in two liver transplant recipients in Iran. The first case was a 34-year old woman who had undergone orthotopic liver transplantation (OLT) at Shiraz Namazi Educational Hospital in 2002. She decided to get pregnant seven years after the operation. During pregnancy, immunosuppressive therapy continued, except Mycophenolate Mofetil which has an absolute contra-indication in pregnancy. The patient was followed up during pregnancy by the transplant team as well as a gynecologist. She faced no significant complications and the liver function was stable during pregnancy. She later underwent a Cesarean section in the 38(th) week of gestation and the newborn was a healthy girl weighing 2480g with an Apgar score of 8 at the time of birth. There were no evidences of prematurity or structural abnormalities in the newborn. The second case was a 31-year old primipara who had received an orthotopic liver transplant (OLT) in Shiraz in 2002. She had a smooth pregnancy without any complications and the newborn was a boy weighing 3100g with Apgar scores of 8 and 10 at the time of birth and 5 minutes thereafter, respectively. As the number of transplant recipients is growing along with the number of recipients who are in their fertility years, it is vital to ensure a proper medical care by a coordinated multidisciplinary team during pregnancy.

  12. Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis.

    Science.gov (United States)

    Oray, Merih; Tuğal-Tutkun, İlknur

    2016-04-01

    Pediatric uveitis may be a serious health problem because of the lifetime burden of vision loss due to severe complications if the problem is not adequately treated. Juvenile idiopathic arthritis (JIA)-associated uveitis is characterized by insidious onset and potentially blinding chronic anterior uveitis. Periodic ophthalmologic screening is of utmost importance for early diagnosis of uveitis. Early diagnosis and proper immunomodulatory treatment are essential for good visual prognosis. The goal of treatment is to achieve enduring drug-free remission. The choice of therapeutic regimen needs to be tailored to each individual case. One must keep in mind that patients under immunomodulatory treatment should be monitored closely due to possible side effects. Local and systemic corticosteroids have long been the mainstay of therapy; however, long-term corticosteroid therapy should be avoided due to serious side effects. Steroid-sparing agents in the treatment of JIA-associated uveitis include antimetabolites and biologic agents in refractory cases. Among the various immunomodulatory agents, methotrexate is generally the first choice, as it has a well-established safety and efficacy profile in pediatric cases and does not appear to increase the risk of cancer. Other classic immunomodulators that may also be used in combination with methotrexate include azathioprine, mycophenolate mofetil, and cyclosporin A. Biologic agents, primarily tumor necrosis factor alpha inhibitors including infliximab or adalimumab, should be considered in cases of treatment failure with classic immunomodulatory agents.

  13. Management of patients with ocular manifestations in vesiculobullous disorders affecting the mouth.

    Science.gov (United States)

    Hansen, M S; Klefter, O N; Julian, H O; Lynge Pedersen, A M; Heegaard, S

    2017-10-01

    Pemphigoid and pemphigus diseases as well as Stevens-Johnson syndrome present as vesiculobullous disorders of the skin and may additionally involve both the oral cavity and the ocular surface. Ocular involvement ranges from mild irritation and dry eye disease to chronic conjunctivitis, symblepharon, eyelid malposition, ocular surface scarring and severe visual loss. In addition to diagnostic assessments, ophthalmologists must treat the dry eye and meibomian gland dysfunction components of these diseases using a stepladder approach, including eyelid hygiene and lubricants. Topical anti-inflammatory therapy is used to treat acute inflammatory exacerbations of the ocular surface, but it cannot prevent scarring alone. Intralesional antimetabolite therapy can cause regression of conjunctival pathology in selected cases. Hence, patients with vesiculobullous disorders should be managed by a multidisciplinary team representing ophthalmology, dermatology, otolaryngology, oral medicine and pathology, internal medicine and intensive care. Systemic treatments including corticosteroids, azathioprine, cyclophosphamide, cyclosporine and mycophenolate mofetil help control inflammation. Intravenous immunoglobulins, plasmapheresis and targeted antibody therapy can be used in selected, severe and treatment-resistant cases. Local surgical management may include debridement of pseudomembranes, lysis of symblepharon, amniotic and mucous membrane grafting as well as reconstructive procedures. Prospective, multicentre, international studies are recommended to further support evidence-based practice. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Combination immunotherapy in the treatment of chronic bilateral panuveitis and uveitic glaucoma during acute dengue fever infection in the Caribbean.

    Science.gov (United States)

    Stewart, Kevin P; Tawakol, Jan B; Khan, Tasnim; Capriotti, Joseph A

    2015-01-01

    Ocular manifestations of the dengue fever virus include bilateral panuveitis that can occur after the acute systemic infection has resolved. In most reported cases, the inflammation resolves with topical or systemic steroid therapy. We report a case of chronic, refractory bilateral panuveitis and uveitic glaucoma that began during the acute phase of the systemic infection and required treatment with oral steroids, multiple steroid-sparing agents, and surgical therapy for glaucoma. A 22-year-old male with acute systemic dengue fever presented with bilateral pain and decreased vision. Clinical examination revealed bilateral panuveitis with elevated intraocular pressures. Management required oral steroids, mycophenolate mofetil, cyclosporine, and bilateral glaucoma valve implantation. This case highlights the fact that dengue-associated panuveitis can begin in the acute stage of systemic infection and persist long after convalescence with progression to chronic bilateral panuveitis and uveitic glaucoma. Dengue-associated chronic panuveitis with uveitic glaucoma may be effectively managed with a combination of steroid-sparing oral immunosuppression and glaucoma surgery. This is, to our knowledge, the first case of bilateral refractory dengue-associated panuveitis from the Caribbean treated with combination steroid-sparing oral immunosuppression and bilateral glaucoma valve implantation.

  15. Autoimmune retinopathy associated with systemic lupus erythematosus: A diagnostic dilemma

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    Wadakarn Wuthisiri

    2017-01-01

    Full Text Available Visual loss in systemic lupus erythematosus (SLE due to autoimmune retinopathy (AIR is rare and easily misdiagnosed as hydroxychloroquine retinopathy. We report the rare clinical presentation of severe visual loss in a patient with SLE due to nonparaneoplastic AIR as differentiated from hydroxychloroquine toxicity. A 70-year-old female diagnosed and treated for lupus for 17 years and had been taking hydroxychloroquine for 15 years. Over the past 2 years, she developed progressive peripheral visual loss oculus uterque which rapidly advanced in the latter 6 months. Hydroxychloroquine toxicity was initially suspected, but diagnostic testing revealed a retinal degeneration. Antiretinal autoantibody testing using Western blot analysis revealed autoantibodies against 44-kDa, 46-kDa (anti-enolase, and 68-kDa proteins. Visual acuity improved in the first 6 months of treatment with mycophenolate mofetil. Our case suggests that AIR should be considered in the differential diagnosis of rapid, severe visual loss in patients with hydroxychloroquine treatment.

  16. Systemic lupus erythematosus associated with type 4 renal tubular acidosis: a case report and review of the literature

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    Young Larry

    2011-03-01

    Full Text Available Abstract Introduction Type 4 renal tubular acidosis is an uncommon clinical manifestation of systemic lupus erythematosus and has been reported to portend a poor prognosis. To the best of our knowledge, this is the first case report which highlights the successful management of a patient with systemic lupus erythematosus complicated by type 4 renal tubular acidosis who did not do poorly. Case presentation A 44-year-old Hispanic woman developed a non-anion gap hyperkalemic metabolic acidosis consistent with type 4 renal tubular acidosis while being treated in the hospital for recently diagnosed systemic lupus erythematosus with multi-organ involvement. She responded well to treatment with corticosteroids, hydroxychloroquine and mycophenolate mofetil. Normal renal function was achieved prior to discharge and remained normal at the patient's one-month follow-up examination. Conclusion This case increases awareness of an uncommon association between systemic lupus erythematosus and type 4 renal tubular acidosis and suggests a positive impact of early diagnosis and appropriate immunosuppressive treatment on the patient's outcome.

  17. Initial Experience with ABO-incompatible Live Donor Renal Transplantation

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    Meng-Kun Tsai

    2006-01-01

    Full Text Available The serious shortage of cadaveric organs has prompted the development of ABO-incompatible live donor renal transplantation. We report our experience of the initial two live donor ABO incompatible renal transplants at our hospital. The first patient was a 55-year-old type A female who received a kidney from her AB type husband. The second patient was a 27-year-old type O male who received renal transplantation from his type A father. Preconditioning immunosuppressive therapy in the two patients with tacrolimus, mycophenolate mofetil and methylprednisolone was started 7 days before transplantation. During the period of preconditioning, double filtration plasmapheresis (DFPP was employed to remove anti-A and -B antibodies. Laparoscopic splenectomy and renal transplantation were performed after the anti-donor ABO antibodies were reduced to a titer of 1:4. Rituximab, a humanized monoclonal anti-CD20 antibody, was administered to the second patient due to a rebound in the anti-A antibody titer during the preconditioning period. Under a tacrolimus-based immunosuppressive regimen, both patients recovered very well without any evidence of rejection. Serum creatinine levels were 1.0 and 1.4 mg/dL at 6 and 3 months after transplantation, respectively. These cases illustrate that with new immunosuppressive agents, DFPP and splenectomy, ABO-incompatible renal transplantation can be successfully conducted in end-stage renal disease patients whose only available live donors are blood group incompatible.

  18. March 2016 imaging case of the month

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    Gotway MB

    2016-03-01

    Full Text Available No abstract available. Article truncated at 150 words. Clinical History: A 66 year-old man with orthotopic heart transplantation 1 year previously presented with complaints of recent-onset small volume (<1 teaspoon hemoptysis, post-nasal drip, and night sweats. The patient indicated he had recent contact with several young grandchildren who had upper respiratory tract symptoms. The patient’s past medical history was remarkable for recurrent constrictive pericarditis (surgically treated, hypertension, type II diabetes mellitus (treated with insulin, psoriasis, sleep-disordered breathing, and grade 2 cardiac transplant rejection diagnosed 6 months earlier. The patient’s medication list included insulin, Cellcept (mycophenolate mofetil, Prograf (tacrolimus, prednisone, among others. On physical examination, the patient was mildly tachycardic (heart rate = 104 beats/minute with an oxygen saturation on room air of 92%. The white blood cell count was within the normal range, but C-reactive protein and B-type natriuretic peptide levels were reportedly elevated. Frontal chest radiography (Figure 1 was performed, with a radiograph from one month other ...

  19. Fertility, pregnancy planning, and pharmacotherapy during the pregnancy, postpartum and breastfeeding period in patients with rheumatoid arthritis and other inflammatory arthropathies

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    Marzena Olesińska

    2014-03-01

    Full Text Available The peak in incidence of the majority of inflammatory arthropathies (IAs is observed in the 2 nd –4 th decades of life. Thus the diseases affect patients at reproductive age. The results of population studies have demonstrated that these diseases can exert effects on the fertility of the patients, family planning, course of pregnancy and further development of the baby. It has also been shown that female patients with IAs, compared with healthy women, less frequently decide to have the first and other babies and the interval between successive pregnancies is longer. The aim of pharmacotherapy in a patient with IA who plans to become pregnant is to effectively inhibit the inflammatory activity and to maintain remission/low activity of the disease during pregnancy and after its termination. Disease-modifying drugs suitable for administration in the preconception period and pregnancy include: chloroquine, hydroxychloroquine, sulfasalazine, azathioprine, ciclosporin A, glucocorticosteroids and non-steroidal anti-inflammatory drugs. The following should not be administered: out of the synthetic disease-modifying drugs – methotrexate, leflunomide, cyclophosphamide and mycophenolate mofetil; and out of biological drugs – abatacept, tocilizumab and rituximab.

  20. The impact of drugs on male fertility: a review.

    Science.gov (United States)

    Semet, M; Paci, M; Saïas-Magnan, J; Metzler-Guillemain, C; Boissier, R; Lejeune, H; Perrin, J

    2017-07-01

    Beside cytotoxic drugs, other drugs can impact men's fertility through various mechanisms. Via the modification of the hypothalamic-pituitary-gonadal axis hormones or by non-hormonal mechanisms, drugs may directly and indirectly induce sexual dysfunction and spermatogenesis impairment and alteration of epididymal maturation. This systematic literature review summarizes existing data about the negative impact and associations of pharmacological treatments on male fertility (excluding cytotoxic drugs), with a view to making these data more readily available for medical staff. In most cases, these effects on spermatogenesis/sperm maturation/sexual function are reversible after the discontinuation of the drug. When a reprotoxic treatment cannot be stopped and/or when the impact on semen parameters/sperm DNA is potentially irreversible (Sulfasalazine Azathioprine, Mycophenolate mofetil and Methotrexate), the cryopreservation of spermatozoa before treatment must be proposed. Deleterious impacts on fertility of drugs with very good or good level of evidence (Testosterone, Sulfasalazine, Anabolic steroids, Cyproterone acetate, Opioids, Tramadol, GhRH analogues and Sartan) are developed. © 2017 American Society of Andrology and European Academy of Andrology.

  1. Ferrets as a Novel Animal Model for Studying Human Respiratory Syncytial Virus Infections in Immunocompetent and Immunocompromised Hosts

    Science.gov (United States)

    Stittelaar, Koert J.; de Waal, Leon; van Amerongen, Geert; Veldhuis Kroeze, Edwin J.B.; Fraaij, Pieter L.A.; van Baalen, Carel A.; van Kampen, Jeroen J.A.; van der Vries, Erhard; Osterhaus, Albert D.M.E.; de Swart, Rik L.

    2016-01-01

    Human respiratory syncytial virus (HRSV) is an important cause of severe respiratory tract disease in immunocompromised patients. Animal models are indispensable for evaluating novel intervention strategies in this complex patient population. To complement existing models in rodents and non-human primates, we have evaluated the potential benefits of an HRSV infection model in ferrets (Mustela putorius furo). Nine- to 12-month-old HRSV-seronegative immunocompetent or immunocompromised ferrets were infected with a low-passage wild-type strain of HRSV subgroup A (105 TCID50) administered by intra-tracheal or intra-nasal inoculation. Immune suppression was achieved by bi-daily oral administration of tacrolimus, mycophenolate mofetil, and prednisolone. Throat and nose swabs were collected daily and animals were euthanized four, seven, or 21 days post-infection (DPI). Virus loads were determined by quantitative virus culture and qPCR. We observed efficient HRSV replication in both the upper and lower respiratory tract. In immunocompromised ferrets, virus loads reached higher levels and showed delayed clearance as compared to those in immunocompetent animals. Histopathological evaluation of animals euthanized 4 DPI demonstrated that the virus replicated in the respiratory epithelial cells of the trachea, bronchi, and bronchioles. These animal models can contribute to an assessment of the efficacy and safety of novel HRSV intervention strategies. PMID:27314379

  2. Ferrets as a Novel Animal Model for Studying Human Respiratory Syncytial Virus Infections in Immunocompetent and Immunocompromised Hosts

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    Koert J. Stittelaar

    2016-06-01

    Full Text Available Human respiratory syncytial virus (HRSV is an important cause of severe respiratory tract disease in immunocompromised patients. Animal models are indispensable for evaluating novel intervention strategies in this complex patient population. To complement existing models in rodents and non-human primates, we have evaluated the potential benefits of an HRSV infection model in ferrets (Mustela putorius furo. Nine- to 12-month-old HRSV-seronegative immunocompetent or immunocompromised ferrets were infected with a low-passage wild-type strain of HRSV subgroup A (105 TCID50 administered by intra-tracheal or intra-nasal inoculation. Immune suppression was achieved by bi-daily oral administration of tacrolimus, mycophenolate mofetil, and prednisolone. Throat and nose swabs were collected daily and animals were euthanized four, seven, or 21 days post-infection (DPI. Virus loads were determined by quantitative virus culture and qPCR. We observed efficient HRSV replication in both the upper and lower respiratory tract. In immunocompromised ferrets, virus loads reached higher levels and showed delayed clearance as compared to those in immunocompetent animals. Histopathological evaluation of animals euthanized 4 DPI demonstrated that the virus replicated in the respiratory epithelial cells of the trachea, bronchi, and bronchioles. These animal models can contribute to an assessment of the efficacy and safety of novel HRSV intervention strategies.

  3. Pre-transplant immune state defined by serum markers and alloreactivity predicts acute rejection after living donor kidney transplantation.

    Science.gov (United States)

    Vondran, Florian W R; Timrott, Kai; Kollrich, Sonja; Steinhoff, Ann-Kristin; Kaltenborn, Alexander; Schrem, Harald; Klempnauer, Juergen; Lehner, Frank; Schwinzer, Reinhard

    2014-09-01

    Acute rejection (AR) remains a major cause for long-term kidney allograft failure. Reliable immunological parameters suitable to define the pre-transplant immune state and hence the individual risk of graft rejection are highly desired to preferably adapt the immunosuppressive regimen in advance. Donor and third party alloreactivities were determined by mixed lymphocyte cultures. Soluble forms of CD25, CD30, and CD44 were detected in patients' serum by ELISA. Various lymphocyte subpopulations were measured using flow cytometry. All patients received triple immunosuppression (tacrolimus/mycophenolate mofetil/steroids) and were grouped according to biopsy results within the first year: rejection-free (RF, n = 13), borderline (BL, n = 5), or acute rejection (AR, n = 7). Patients with AR showed the highest pre-transplant alloreactivities and serum levels (sCD25/sCD30/sCD44) according to the pattern RF transplant frequencies of CD4(+) /CD8(+) T cells lacking CD28, but lower numbers of CD8(+) CD161(bright) T cells and NK cells than RF individuals. Pre-transplant immune state defined by alloreactivity, serum markers, and particular lymphocyte subsets seems to correlate with occurrence of graft rejection after kidney transplantation. A prognostic score based on pre-transplant serum levels has shown great potential for prediction of rejection episodes and should be further evaluated. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Challenges in renal transplantation in Yemen.

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    El-Nono, Ibrahiem H; Telha, Khaled A; Al-Alimy, Gamil M; Ghilan, Abdulilah M; Abu Asba, Nagieb W; Al-Zkri, Abdo M; Al-Adimi, Abdulilah M; Al-Ba'adani, Tawfiq H

    2015-02-16

    Background Renal replacement therapy was first introduced in Yemen in 1978 in the form of hemodialysis. Twenty years later, the first renal transplantation was performed. Kidney transplantations were started in socially and financially challenging circumstances in Yemen in 1998. A structured program was established and has been functioning regularly since 2005. A pediatric transplantation program was started in 2011. Material and Methods This was a prospective study of 181 transplants performed at the Urology and Nephrology Center between May 1998 and 2012. All transplants were from living related donors. The immunosuppressive protocol consisted initially of double therapy with steroid and mycophenolate mofetil (MMF). Subsequently, triple therapy with addition of a calcineurin inhibitor was introduced. Primary graft function was achieved in 176 (97.2%) recipients. Results Cold ischemia time was 48-68 min. Episodes of acute rejection in 12 patients were treated with high-dose steroids. Anti-thymocyte globulin (ATG) was used in cases of vascular or steroid-resistant rejection in 2 patients. The post-transplant complications, either surgical or medical, were comparable to those recorded in the literature. Conclusions Renal transplantation is a good achievement in our country. The patients and graft survival rates are comparable to other reports.

  5. Characterization of Novel PI3Kδ Inhibitors as Potential Therapeutics for SLE and Lupus Nephritis in Pre-Clinical Studies.

    Science.gov (United States)

    Haselmayer, Philipp; Camps, Montserrat; Muzerelle, Mathilde; El Bawab, Samer; Waltzinger, Caroline; Bruns, Lisa; Abla, Nada; Polokoff, Mark A; Jond-Necand, Carole; Gaudet, Marilène; Benoit, Audrey; Bertschy Meier, Dominique; Martin, Catherine; Gretener, Denise; Lombardi, Maria Stella; Grenningloh, Roland; Ladel, Christoph; Petersen, Jørgen Søberg; Gaillard, Pascale; Ji, Hong

    2014-01-01

    SLE is a complex autoimmune inflammatory disease characterized by pathogenic autoantibody production as a consequence of uncontrolled T-B cell activity and immune-complex deposition in various organs, including kidney, leading to tissue damage and function loss. There is a high unmet need for better treatment options other than corticosteroids and immunosuppressants. Phosphoinositol-3 kinase δ (PI3Kδ) is a promising target in this respect as it is essential in mediating B- and T-cell function in mouse and human. We report the identification of selective PI3Kδ inhibitors that blocked B-, T-, and plasmacytoid dendritic cell activities in human peripheral blood and in primary cell co-cultures (BioMAP(®)) without detecting signs of undesired toxicity. In an IFNα-accelerated mouse SLE model, our PI3Kδ inhibitors blocked nephritis development, whether administered at the onset of autoantibody appearance or the onset of proteinuria. Disease amelioration correlated with normalized immune cell numbers in the spleen, reduced immune-complex deposition as well as reduced inflammation, fibrosis, and tissue damage in the kidney. Improvements were similar to those achieved with a frequently prescribed drug for lupus nephritis, the potent immunosuppressant mycophenolate mofetil. Finally, we established a pharmacodynamics/pharmacokinetic/efficacy model that revealed that a sustained PI3Kδ inhibition of 50% is sufficient to achieve full efficacy in our disease model. These data demonstrate the therapeutic potential of PI3Kδ inhibitors in SLE and lupus nephritis.

  6. Developing standardised treatment for adults with myositis and different phenotypes: an international survey of current prescribing preferences.

    Science.gov (United States)

    Tansley, Sarah; Shaddick, Gavin; Christopher-Stine, Lisa; Sharp, Charlotte; Dourmishev, Lyubomir; Maurer, Britta; Chinoy, Hector; McHugh, Neil

    2016-01-01

    The evidence base for treatment of the idiopathic inflammatory myopathies is extremely limited. The rarity and heterogeneity of these diseases has hampered the development of good quality clinical trials and while a range of immunomodulatory treatments are commonly used in clinical practice, as yet there are no clear guidelines directing their use. We aimed to establish current prescribing regimens used to treat adults with myositis internationally. An electronic survey based on different clinical scenarios was distributed internationally to clinicians involved in the treatment of patients with myositis. Participants were asked to select their first-line treatment preferences in each situation. A multinomial regression analysis was used to assess the influence of clinical scenario, respondent expertise and country of origin on first-line treatment choice. 107 survey responses were received. 57% of respondents considered themselves an expert in myositis and the majority of respondents were rheumatologists although responses from other specialities were also received. Pharmacological treatment with steroids and additional immunotherapy was the preference in most scenarios. First-line immunosuppressant choice was significantly influenced by the clinical scenario, the expertise of the treating physician and country of practice. Azathioprine, methotrexate and mycophenolate mofetil were the most commonly chosen agents. In the absence of available evidence, clinical experience and expert consensus often forms the basis of treatment guidelines. These results suggest that an international consensus approach would be possible in myositis and would overcome an urgent, yet unmet need for patients suffering with this difficult disease.

  7. Update on the pharmacological treatment of adult myositis.

    Science.gov (United States)

    Oddis, C V

    2016-07-01

    The management of patients with idiopathic inflammatory myopathy (IIM) remains a challenge given the systemic features beyond active myositis. That is, recognizing the inflammatory arthropathy, varying dermatomyositis rashes, and overt and occult features of interstitial lung disease in addition to myositis adds to the complexity of diagnosis and treatment of IIM. However, clinicians now have available many more immunosuppressive drugs as well as biologic agents for use in patients with myositis and other autoimmune diseases. Here, the use of these agents is reviewed and support based on available published literature is provided even though many studies have been small and results somewhat anecdotal. Glucocorticoids remain the initial treatment of choice in most instances and methotrexate and azathioprine are often used early in the treatment course. These agents are followed by other immunosuppressive drugs, for example mycophenolate mofetil, tacrolimus, cyclosporine and cyclophosphamide, some of which are used alone while combinations of these agents also provide an effective option. There is more rationale for the use of biologic agents such as rituximab from a mechanistic perspective and, given the incorporation of validated core set measures in assessing myositis patients, we can look forward to better designed clinical trials in the future. © 2016 The Association for the Publication of the Journal of Internal Medicine.

  8. Prevalence and association of post-renal transplant anemia

    Directory of Open Access Journals (Sweden)

    Hesham Elsayed

    2012-01-01

    Full Text Available In some renal allograft recipients, anemia persists or develops following transplantation. Anemia is associated with pre-operative blood loss and allograft dysfunction, including delayed graft function, acute rejection and chronic allograft dysfunction. To study the prevalence and association of post-renal transplant anemia, we studied 200 renal transplant recipients; 131 (65.5% patients were males and 69 (34.5% patients were females, and age ranged from 17 to 67 years, with a mean of 37.7 ± 10.8 years. All patients were receiving cyclosporine, prednisolone and mycophenolate mofetil (MMF. Complete blood count was done at two times: three and six months post-renal transplant. There were 74% anemic patients three months after renal transplantation and 45% anemic patients six months after renal transplantation. High creatinine value, female gender, delayed graft function, episodes of acute rejection, perioperative blood loss and infections were the only significant independent risk factors for prevalence of anemia post-renal transplant. In our study, we did not find an association between MMF and cyclosporine nor angiotensin-converting enzyme inhibitors (ACEIs or angiotensin receptors blocker (ARBs with anemia. This study demonstrates that anemia is a common complication during the first six months after kidney transplantation, with several risk factors precipitating this complication.

  9. The International Registry on Hand and Composite Tissue Transplantation.

    Science.gov (United States)

    Petruzzo, Palmina; Lanzetta, Marco; Dubernard, Jean-Michel; Landin, Luis; Cavadas, Pedro; Margreiter, Raimund; Schneeberger, Stephan; Breidenbach, Warren; Kaufman, Christina; Jablecki, Jerzy; Schuind, Frédéric; Dumontier, Christian

    2010-12-27

    The International Registry on Hand and Composite Tissue Transplantation was founded in May 2002, and the analysis of all cases with follow-up information up to July 2010 is presented here. From September 1998 to July 2010, 49 hands (17 unilateral and 16 bilateral hand transplantations, including 1 case of bilateral arm transplantation) have been reported, for a total of 33 patients. They were 31 men and 2 women (median age 32 years). Time since hand loss ranged from 2 months to 34 years, and in 46% of cases, the level of amputation was at wrist. Immunosuppressive therapy included tacrolimus, mycophenolate mofetil, sirolimus, and steroids; polyclonal or monoclonal antibodies were used for induction. Topical immunosuppression was also used in several cases. Follow-up ranges from 1 month to 11 years. One patient died on day 65. Three patients transplanted in the Western countries have lost their graft, whereas until September 2009, seven hand grafts were removed for noncompliance to the immunosuppressive therapy in China. Eighty-five percent of recipients experienced at least one episode of acute rejection within the first year, and they were reversible when promptly treated. Side effects included opportunistic infections, metabolic complications, and malignancies. All patients developed protective sensibility, 90% of them developed tactile sensibility, and 82.3% also developed a discriminative sensibility. Motor recovery enabled patients to perform most daily activities. Hand transplantation is a complex procedure, and its success is based on patient's compliance and his or her careful evaluation before and after transplantation.

  10. Treatment of Intraepidermal Autoimmune Bullous Diseases Sürekli Eğitim

    Directory of Open Access Journals (Sweden)

    Tamer İrfan Kaya

    2011-06-01

    Full Text Available Pemfigus is an autoimmune bullous skin disease, characterized by intraepidermal blisters. It is a severe and potentially life-threatening chronic disease with blisters and erosions on the mucosae and the skin. Treatment options do not differ for two most common types of pemphigus, pemphigus vulgaris and pemphigus foliaceus, except that the latter is usually less resistant to treatment and corticosteroids can often be started at lower doses. Systemic corticosteroids are still the most widely used drugs in the treatment of pemphigus and continue to be the mainstay of therapy for this disease. Adjuvant drugs are commonly used in combination with the aims of increasing efficacy and of having a steroid-sparing action, thereby allowing reduced corticosteroid side-effects. Mortality and complete remission rates have improved since the introduction of adjuvant drugs to pemphigus. Adjuvant drugs include immunoadsorbtion, corticosteroid pulse therapy, intravenous immunoglobulin (IVIG, immunosuppressive agents such as azathioprine, cyclophosphamide, mycophenolate mofetil and and anti-CD20 monoclonal antibody (rituximab. The lack of consensus in the published literature about the treatment of this disorder is responsible for different treatment strategies. Treatments need to be chosen after careful consideration of the potential benefits and side effects according to the patients’ medical condition. Here, both conventional therapies and novel treatment regimens for pemphigus are discussed. (Turkderm 2011; 45 Suppl 1: 44-53

  11. Type III Mixed Cryoglobulinemia and Antiphospholipid Syndrome in a Patient With Partial DiGeorge Syndrome

    Directory of Open Access Journals (Sweden)

    Alice D. Chang

    2006-01-01

    Full Text Available We studied a 14 year-old boy with partial DiGeorge syndrome (DGS, status post complete repair of Tetralogy of Fallot, who developed antiphospholipid syndrome (APS and type III mixed cryoglobulinemia. He presented with recurrent fever and dyspnea upon exertion secondary to right pulmonary embolus on chest computed tomography (CT. Coagulation studies revealed homozygous methylene tetrahydrofolate reductase 677TT mutations, elevated cardiolipin IgM antibodies, and elevated β2-glycoprotein I IgM antibodies. Infectious work-up revealed only positive anti-streptolysin O (ASO and anti-DNAse B titers. Autoimmune studies showed strongly positive anti-platelet IgM, elevated rheumatoid factor (RF, and positive cryocrit. Renal biopsy for evaluation of proteinuria and hematuria showed diffuse proliferative glomerulonephritis (DPGN with membranoproliferative features consistent with cryoglobulinemia. Immunofixation showed polyclonal bands. Our patient was treated successfully with antibiotics, prednisone, and mycophenolate mofetil (MMF. This is the first report of a patient with partial DGS presenting with APS and type III mixed cryoglobulinemia possibly due to Streptococcal infection.

  12. Incidence and Pattern of Graft-versus-Host Disease in Patients Undergoing Allogeneic Transplantation after Nonmyeloablative Conditioning with Total Lymphoid Irradiation and Antithymocyte Globulin

    Directory of Open Access Journals (Sweden)

    Lauren Veltri

    2013-01-01

    Full Text Available Nonmyeloablative (NMA conditioning with total lymphoid irradiation and antithymocyte globulin (TLI/ATG has been shown to protect against acute graft-versus-host disease (GVHD. We report here our institutional experience with allogeneic transplantation following NMA conditioning with TLI/ATG (. GVHD prophylaxis consisted of a combination of a calcineurin inhibitor and mycophenolate mofetil. Median patient age was 59 years. The median followup of surviving patients is 545 days. One patient experienced primary graft rejection. The median time to neutrophil engraftment was 18 days and platelet engraftment was 9.5 days. The cumulative incidence (CI of grade II–IV acute GVHD at day +100 was 28.6% and 38.1% at day +180. The CI for grade III-IV acute GVHD was 28.6% at day +180. CI of chronic GVHD was 45.2% at 1 year. The CI of disease relapse was 9.5% at 1 year. The rate of nonrelapse mortality (NRM was 0% at day +100 and only 9.5% at 1 year. The overall and progression free survival at 1 year was 81% and 80.4%, respectively. Our limited, retrospective data show encouraging relapse and NRM rates with TLI/ATG-based NMA conditioning, but with higher than previously reported rates of acute and chronic GVHD, underscoring the need for novel strategies designed to effectively prevent GVHD.

  13. Gastrointestinal Bleeding and Diffuse Skin Thickening as Kaposi Sarcoma Clinical Presentation

    Directory of Open Access Journals (Sweden)

    Sara Querido

    2015-01-01

    Full Text Available A 56-year-old African patient received a kidney from a deceased donor with 4 HLA mismatches in April 2013. He received immunosuppression with basiliximab, tacrolimus, mycophenolate mofetil, and prednisone. Immediate diuresis and a good allograft function were soon observed. Six months later, the serum creatinine level increased to 2.6 mg/dL. A renal allograft biopsy revealed interstitial fibrosis and tubular atrophy grade II. Toxicity of calcineurin inhibitor was assumed and, after a switch for everolimus, renal function improved. However, since March 2014, renal function progressively deteriorated. A second allograft biopsy showed no new lesions. Two months later, the patient was admitted due to anuria, haematochezia with anaemia, requiring 5 units of packed red blood cells, and diffuse skin thickening. Colonoscopy showed haemorrhagic patches in the colon and the rectum; histology diagnosis was Kaposi sarcoma (KS. A skin biopsy revealed cutaneous involvement of KS. Rapid clinical deterioration culminated in death in June 2014. This case is unusual as less than 20 cases of KS with gross gastrointestinal bleeding have been reported and only 6 cases had the referred bleeding originating in the lower gastrointestinal tract. So, KS should be considered in differential diagnosis of gastrointestinal bleeding in some kidney transplant patients.

  14. Contemporary issues and future directions in autoimmune hepatitis.

    Science.gov (United States)

    Liberal, Rodrigo; Mieli-Vergani, Giorgina; Vergani, Diego

    2016-06-03

    Autoimmune hepatitis (AIH) is a severe life-threatening hepatopathy of unknown etiology, affecting both pediatric and adult populations, and characterised by inflammatory liver histology, circulating non-organ-specific autoantibodies, and hypergammaglobulinaemia. AIH is a very heterogeneous disease with a variety of clinical presentations, ranging from asymptomatic liver test abnormalities to acute severe hepatitis or even acute liver failure. It responds very well to immunosuppressive treatment with prednisolone with or without azathioprine. Patients who are intolerant or fail to respond to standard therapy are candidates for alternative immunosuppressive regimens, the combination of steroids with mycophenolate mofetil or calcineurin inhibitors being the most frequently reported. The pathogenesis of AIH remains not completely understood, although there is evidence that genetic predisposition, molecular mimicry and defective immunoregulatory mechanisms contribute to the autoimmune liver damage. A literature search was conducted using the key-words 'autoimmune hepatitis', 'immunogenetics', 'regulatory T-cells' and 'immunosuppression'. The aim of this review is to discuss recent breakthroughs in the understanding AIH pathogenesis, diagnosis and treatment. Expert commentary: Progress in the understanding of AIH pathogenesis is likely to contribute to the development of novel therapeutic strategies, such as the adoptive transfer of autologous expanded antigen-specific regulatory T-cells.

  15. Current methods of the analysis of immunosuppressive agents in clinical materials: A review.

    Science.gov (United States)

    Mika, Adriana; Stepnowski, Piotr

    2016-08-05

    More than 100000 solid organ transplantations are performed every year worldwide. Calcineurin (cyclosporine A, tacrolimus), serine/threonine kinase (sirolimus, everolimus) and inosine monophosphate dehydrogenase inhibitor (mycophenolate mofetil), are the most common drugs used as immunosuppressive agents after solid organ transplantation. Immunosuppressive therapy, although necessary after transplantation, is associated with many adverse consequences, including the formation of secondary metabolites of drugs and the induction of their side effects. Calcineurin inhibitors are associated with nephrotoxicity, cardiotoxicity and neurotoxicity; moreover, they increase the risk of many diseases after transplantation. The review presents a study of the movement of drugs in the body, including the processes of absorption, distribution, localisation in tissues, biotransformation and excretion, and also their accompanying side effects. Therefore, there is a necessity to monitor immunosuppressants, especially because these drugs are characterised by narrow therapeutic ranges. Their incorrect concentrations in a patient's blood could result in transplant rejection or in the accumulation of toxic effects. Immunosuppressive pharmaceuticals are macrolide lactones, peptides, and high molecular weight molecules that can be metabolised to several metabolites. Therefore the two main analytical methods used for their determination are high performance liquid chromatography with various detection methods and immunoassay methods. Despite the rapid development of new analytical methods of analysing immunosuppressive agents, the application of the latest generation of detectors and increasing sensitivity of such methods, there is still a great demand for the development of highly selective, sensitive, specific, rapid and relatively simple methods of immunosuppressive drugs analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Pregnancy in renal transplant recipients.

    Science.gov (United States)

    Bouattar, T; Hakim, H; Rhou, H; Benamar, L; Bayahia, R; Ouzeddoun, N

    2009-06-01

    Renal transplantation with a well-functioning graft leads to a rapid restoration of endocrine and sexual functions. The aim of this study was to examine our experience with pregnancies among renal transplant patients, particularly with regard to their impact on graft function. We analyzed 10 pregnancies in 7 renal transplant recipients for long-term graft outcomes in terms of clinical and biological data. The mean patient age was 28.5 +/- 4 years. They all received a living donor kidney. The time between transplantation and the onset of pregnancy was 33.4 +/- 23.2 months. Regarding the immunosuppressive therapy, all patients received steroids and cyclosporine; 4 patients received in addition azathioprine and 2 received mycophenolate mofetil that was changed at 1 month before conception to azathioprine. There was no significant difference between the serum creatinine before and during pregnancy. We did not observe any acute rejection episode. Pregnancy complications were preclampsia in 1 case, hypertension in 1 case, urinary tract infection in 2 cases, and anemia in 80% of patients during the third trimester. Premature rupture of membranes occurred in 1 case and preterm delivery in 2 cases. Two cases of neonatal death were registered. Cesarean section was performed in 50% of cases. The follow-up revealed 2 cases of chronic rejection. A multidisciplinary approach is necessary for pregnancy which generally occurs at 2 years after kidney transplantation.

  17. Treatment of neuromyelitis optica: an evidence based review

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    Douglas Sato

    2012-01-01

    Full Text Available Neuromyelitis optica (NMO is an inflammatory disease of the central nervous system characterized by severe optic neuritis and transverse myelitis, usually with a relapsing course. Aquaporin-4 antibody is positive in a high percentage of NMO patients and it is directed against this water channel richly expressed on foot processes of astrocytes. Due to the severity of NMO attacks and the high risk for disability, treatment should be instituted as soon as the diagnosis is confirmed. There is increasing evidence that NMO patients respond differently from patients with multiple sclerosis (MS, and, therefore, treatments for MS may not be suitable for NMO. Acute NMO attacks usually are treated with high dose intravenous corticosteroid pulse and plasmapheresis. Maintenance therapy is also required to avoid further attacks and it is based on low-dose oral corticosteroids and non-specific immunosuppressant drugs, like azathioprine and mycophenolate mofetil. New therapy strategies using monoclonal antibodies like rituximab have been tested in NMO, with positive results in open label studies. However, there is no controlled randomized trial to confirm the safety and efficacy for the drugs currently used in NMO.

  18. Enzymatic Activity of Candida spp. from Oral Cavity and Urine in Children with Nephrotic Syndrome.

    Science.gov (United States)

    Olczak-Kowalczyk, Dorota; Roszkowska-Blaim, Maria; Dąbkowska, Maria; Swoboda-Kopeć, Ewa; Gozdowski, Dariusz; Mizerska-Wasiak, Małgorzata; Demkow, Urszula; Pańczyk-Tomaszewska, Małgorzata

    2017-01-01

    Oral colonization with Candida spp. is not synonymous with a systemic active infection. The aim of the study was to evaluate enzymatic activity of Candida strains isolated from the oral cavity in patients with nephrotic syndrome (NS) and to compare it with the activity determined in urine. We studied 32 children with NS and 26 control healthy children. Children with NS were treated with glucocorticosteroids, cyclosporin A, mycophenolate mofetil or azathioprine. In all children, API-ZYM enzymatic tests were performed to evaluate hydrolytic enzymes of Candida isolated from the oral cavity and in urine. Candida spp. were isolated from the oral cavity in 11 patients with NS (34.4%), all receiving immunosuppressive treatment. All strains produced valine arylamidase, 9 alpha-glucosidase (E16), and 9 N-acetyl-beta-glucosaminidase (E18). A positive correlation between the presence of Candida in the oral cavity and E16 and E18 enzymatic activity in both oral cavity and urine was found. A dose of cyclosporin A had an effect on the enzymatic activity (p Candida invasion. The results of this study suggest that oral candida infection should be monitored in children with nephrotic syndrome, particularly those treated with immunosuppressive agents.

  19. Successful management of Churg-Strauss syndrome using omalizumab as adjuvant immunomodulatory therapy: first documented pediatric case.

    Science.gov (United States)

    Iglesias, E; Camacho Lovillo, M; Delgado Pecellín, I; Lirola Cruz, M J; Falcón Neyra, M D; Salazar Quero, J C; Bernabeu-Wittel, J; González Valencia, J P; Neth, O

    2014-03-01

    Churg-Strauss syndrome (CSS) is an anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis; it is extremely rare in childhood and defined according to the Chapel-Hill Consensus as an eosinophil-rich and granulomatous inflammation involving the respiratory tract and necrotizing vasculitis affecting small to medium-sized vessels. Children commonly have a history of asthma and sinusitis whilst clinical presentation typically involves pulmonary tract and less frequently skin, heart, gastrointestinal tract, and peripheral nerves. Cardiopulmonary disease is higher in children and prognosis is worse. It is associated with significant eosinophilia and raised serum IgE-levels. ANCA are only found in 25% of childhood cases. Here we report the case of a 10-year-old girl who presented to us with vomiting, abdominal pain, and weight loss, paresthesias of lower extremities and breathlessness as well as a history of asthma, sinusitis and allergic rhinitis. She was treated with corticosteroids, cyclophosphamide, intravenous immunoglobulin, mycophenolate mofetil (MMF), and rituximab. However, remission was only achieved after initiation of omalizumab therapy, a recombinant humanized anti-IgE antibody. To the best of our knowledge this is the first pediatric patient suffering from CSS successfully managed with adjuvant anti-IgE therapy resulting in the control of respiratory as well as gastrointestinal symptoms. © 2013 Wiley Periodicals, Inc.

  20. Higher tacrolimus trough levels on days 2-5 post-renal transplant are associated with reduced rates of acute rejection.

    LENUS (Irish Health Repository)

    O'Seaghdha, C M

    2011-04-06

    We analyzed the association between whole-blood trough tacrolimus (TAC) levels in the first days post-kidney transplant and acute cellular rejection (ACR) rates. Four hundred and sixty-four consecutive, deceased-donor kidney transplant recipients were included. All were treated with a combination of TAC, mycophenolate mofetil and prednisolone. Patients were analyzed in four groups based on quartiles of the mean TAC on days 2 and 5 post-transplant: Group 1: median TAC 11 ng\\/mL (n = 122, range 2-13.5 ng\\/mL), Group 2: median 17 ng\\/mL (n = 123, range 14-20 ng\\/mL), Group 3: median 24 ng\\/mL (n = 108, range 20.5-27 ng\\/mL) and Group 4: median 33.5 ng\\/mL (n = 116, range 27.5-77.5 ng\\/mL). A graded reduction in the rates of ACR was observed for each incremental days 2-5 TAC. The one-yr ACR rate was 24.03% (95% CI 17.26-32.88), 22.20% (95% CI 15.78-30.70), 13.41% (95% CI 8.15-21.63) and 8.69% (95% CI 4.77-15.55) for Groups 1-4, respectively (p = 0.003). This study suggests that higher early TACs are associated with reduced rates of ACR at one yr.

  1. Effects of different anti-rejection drugs and projects on dyslipidemia after organ transplantation%抗器官排斥药物和方案对器官移植术后血脂变化的影响

    Institute of Scientific and Technical Information of China (English)

    薛孟娟; 吕朝阳; 张尧; 何顺梅; 于明香

    2015-01-01

    [Summary] Dyslipidemia after organ transplantation is one of the important risk factors of postoperative cardiovascular disease and graft dysfunction. There are many factors that result in postoperative dyslipidemia. However, the factors influencing serum lipid levels are changing with the development of organ transplantation. In this article the effects of different anti-rejection drugs such as cyclosporine, azathioprine, mycophenolate mofetil, tacrolimus, rapamycin ( sirolimus ) , corticosteroids, and monoclonal antibody on dyslipidemia after organ transplantation were summarized in different eras.%器官移植术后血脂异常是器官移植术后心血管疾病及移植物失功的重要危险因素之一。影响器官移植术后血脂变化的因素很多,然而随着器官移植的发展,不同年代影响术后血脂变化的因素也有所改变。本文综述了不同年代抗器官排斥药物包括环孢素、硫唑嘌呤、霉酚酸酯、他克莫司、雷帕霉素(西罗莫司)、激素以及单抗等免疫抑制剂应用的不同对术后受者血脂的影响。

  2. Pyoderma gangrenosum: A commonly overlooked ulcerative condition

    Directory of Open Access Journals (Sweden)

    Daniel Zunsheng Tay

    2014-01-01

    Full Text Available Background: Pyoderma ga ngrenosum (PG is a rare, inflammatory, destructive neutrophilic dermatosis, which mimics other ulcerative conditions. Materials and Methods: In a retrospective study based on patients diagnosed with PG over a 3-year period (2010-2013, we evaluated demographics, anatomical sites, number of lesions, subtypes, histopathology, associated conditions, treatment regimens, healing time, and recurrence. Results: Of our five patients, there were three males and two females, age ranging between 19 and 58 years (mean age 38 years. Four had single lesions localized to the lower limbs while one had multiple lesions (more than five over bilateral hands and legs. Ulcerative subtype was observed in all the patients. One exhibited pathergy. Skin biopsies were done in four patients, revealing dense neutrophilic infiltrates in three cases and leukocytoclastic vasculitis in one. Associated systemic diseases were observed in all patients, four having inflammatory bowel disease and one having both systemic lupus erythematosus and anti-phospholipid syndrome. The patients were all treated with systemic corticosteroids either alone or in combination with immunosuppressants (e.g., azathioprine, mycophenolate mofetil, tacrolimus, and wound dressing. Split-thickness skin graft was done in one patient. Complete healing was achieved in all patients, ranging from one to 3 months after diagnosis. No recurrence was reported. Conclusions: Systemic corticosteroids, either alone or in combination with steroid-sparing agents are the mainstay of treatment. Should family physicians encounter a rapidly progressing ulcer that has poor response to usual wound management, timely referral to dermatology should be made.

  3. Myasthenia gravis: an update for the clinician

    Science.gov (United States)

    Sieb, J P

    2014-01-01

    This paper provides a thorough overview of the current advances in diagnosis and therapy of myasthenia gravis (MG). Nowadays the term ‘myasthenia gravis’ includes heterogeneous autoimmune diseases, with a postsynaptic defect of neuromuscular transmission as the common feature. Myasthenia gravis should be classified according to the antibody specificity [acetylcholine, muscle-specific receptor tyrosine kinase (MuSK), low-density lipoprotein receptor-related protein 4 (LRP4), seronegative], thymus histology (thymitis, thymoma, atrophy), age at onset (in children; aged less than or more than 50 years) and type of course (ocular or generalized). With optimal treatment, the prognosis is good in terms of daily functions, quality of life and survival. Symptomatic treatment with acetylcholine esterase inhibition is usually combined with immunosuppression. Azathioprine still remains the first choice for long-term immunosuppressive therapy. Alternative immunosuppressive options to azathioprine include cyclosporin, cyclophosphamide, methotrexate, mycophenolate mofetil and tacrolimus. Rituximab is a promising new drug for severe generalized MG. Emerging therapy options include belimumab, eculizumab and the granulocyte– macrophage colony-stimulating factor. One pilot study on etanercept has given disappointing results. For decades, thymectomy has been performed in younger adults to improve non-paraneoplastic MG. However, controlled prospective studies on the suspected benefit of this surgical procedure are still lacking. In acute exacerbations, including myasthenic crisis, intravenous immunoglobulin, plasmapheresis and immunoadsorption are similarly effective. PMID:24117026

  4. Understanding lupus nephritis: diagnosis, management, and treatment options

    Directory of Open Access Journals (Sweden)

    Mok CC

    2012-05-01

    Full Text Available Chi Chiu MokDepartment of Medicine, Tuen Mun Hospital and Center for Assessment and Treatment of Rheumatic Diseases, Pok Oi Hospital, Hong Kong, ChinaAbstract: Systemic lupus erythematosus (SLE predominantly affects women in their reproductive years. Renal disease (glomerulonephritis is one of the most frequent and serious manifestations of SLE. Of the various histological types of lupus glomerulonephritis, diffuse proliferative nephritis carries the worst prognosis. Combined with high-dose prednisone, mycophenolate mofetil (MMF has emerged as a first-line immunosuppressive treatment, although data regarding the efficacy of MMF on the long-term preservation of renal function are forthcoming. Cyclophosphamide is reserved for more severe forms of lupus nephritis, such as crescentic glomerulonephritis with rapidly deteriorating renal function, patients with significant renal function impairment at presentation, and refractory renal disease. Evidence for the calcineurin inhibitors in the treatment of lupus nephritis is weaker, and it concerns patients who are intolerant or recalcitrant to other agents. While further controlled trials are mandatory, B cell modulation therapies, such as rituximab, belimumab and epratuzumab are confined to refractory disease. Non-immunosuppressive measures, such as angiotensin-converting enzyme inhibitors, vigorous blood pressure control, prevention and treatment of hyperlipidemia and osteoporosis, are equally important.Keywords: lupus, nephritis, nephropathy, glomerulonephritis, treatment, therapy, women

  5. Current and emerging treatment options in the management of lupus

    Science.gov (United States)

    Jordan, Natasha; D’Cruz, David

    2016-01-01

    Systemic lupus erythematosus (SLE) is a complex autoimmune disease with variable clinical manifestations. While the clearest guidelines for the treatment of SLE exist in the context of lupus nephritis, patients with other lupus manifestations such as neuropsychiatric, hematologic, musculoskeletal, and severe cutaneous lupus frequently require immunosuppression and/or biologic therapy. Conventional immunosuppressive agents such as mycophenolate mofetil, azathioprine, and cyclophosphamide are widely used in the management of SLE with current more rationalized treatment regimens optimizing the use of these agents while minimizing potential toxicity. The advent of biologic therapies has advanced the treatment of SLE particularly in patients with refractory disease. The CD20 monoclonal antibody rituximab and the anti-BLyS agent belimumab are now widely in use in clinical practice. Several other biologic agents are in ongoing clinical trials. While immunosuppressive and biologic agents are the foundation of inflammatory disease control in SLE, the importance of managing comorbidities such as cardiovascular risk factors, bone health, and minimizing susceptibility to infection should not be neglected. PMID:27529058

  6. PML and rheumatology: the contribution of disease and drugs.

    LENUS (Irish Health Repository)

    Molloy, Eamonn S

    2011-11-01

    Progressive multifocal leukoencephalopathy (PML), a rare, typically fatal, opportunistic infection caused by the JC virus, is becoming relevant to physicians in multiple specialties, including those who prescribe biologic agents for the treatment of autoimmune disorders. Reports of PML have led to US Food and Drug Administration alerts and warning letters regarding four immunosuppressive agents in recent years (natalizumab, rituximab, efalizumab, and mycophenolate mofetil). Consequently, informed clinical decision-making requires understanding the risk of PML associated with these therapies. An estimate of the relative frequency of PML associated with specific rheumatic conditions has been generated. Systemic lupus erythematosus appears to be associated with susceptibility to PML that cannot be fully explained by the intensity of immunosuppressive therapy. Further, the use of rituximab in patients with rheumatic disease has raised concerns. However, definitive attribution of cause is precluded by the limitations of the currently available data. All patients with rheumatic disease, regardless of the intensity of their current immunosuppressive therapy, should be considered potentially at risk of PML. With an evolving understanding of a greater clinical heterogeneity of PML, advances in diagnostic methods, and significant implications for therapy, PML should be considered in the differential diagnosis of neurologic manifestations of rheumatic diseases.

  7. Changes in Composition of the Gut Bacterial Microbiome after Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection in a Pediatric Heart Transplant Patient.

    Science.gov (United States)

    Flannigan, Kyle L; Rajbar, Taylor; Moffat, Andrew; McKenzie, Leanna S; Dicke, Frank; Rioux, Kevin; Workentine, Matthew L; Louie, Thomas J; Hirota, Simon A; Greenway, Steven C

    2017-01-01

    The microbiome is increasingly recognized as an important influence on human health and many of the comorbidities that affect patients after solid organ transplantation (SOT) have been shown to involve changes in gut bacterial populations. Thus, microbiome changes in an individual patient may have important health implications after SOT but this area remains understudied. We describe changes in the composition of the fecal microbiome from a pediatric heart transplant recipient before and >2.5 years after he underwent repeated fecal microbiota transplantation (FMT) for recurrent Clostridium difficile infection (CDI). With both documented episodes of CDI, there was marked loss of bacterial diversity with overgrowth of Proteobacteria (>98.9% of phyla identified) associated with symptomatic colitis that was corrected after FMT. We hypothesize that a second CDI occurring after FMT was related to incomplete restoration of normal bowel flora post-FMT with relative deficiencies of the phyla Firmicutes and Bacteroidetes and the families Lachnospiraceae and Ruminococcaceae . Following the second FMT, there was a gradual shift in gut bacterial composition coincident with the recipient developing lymphonodular hyperplasia of the colon and painless hematochezia that resolved with discontinuation of mycophenolate mofetil (MMF). This case documents dynamic changes in the bacterial microbiome after FMT and suggests that MMF may influence the gut microbiome with consequences for the patient.

  8. Impact of the National Institutes of Health Focal Segmental Glomerulosclerosis (NIH FSGS) clinical trial on the treatment of steroid-resistant FSGS.

    Science.gov (United States)

    Canetta, Pietro A; Radhakrishnan, Jai

    2013-03-01

    Idiopathic focal segmental glomerulosclerosis (FSGS) is among the most common, morbid and treatment-resistant conditions faced by nephrologists. While glucocorticoids have traditionally been the mainstay of initial treatment, they induce remission in only a minority of patients. A variety of other immunosuppressants have been utilized against steroid-resistant FSGS, but few have been rigorously examined in well-controlled trials. Recently, the results were published from a National Institutes of Health (NIH)-sponsored multicenter randomized trial comparing cyclosporine (CSA) with a combination of mycophenolate mofetil (MMF) and pulse dexamethasone (DEX) for the treatment of steroid-resistant FSGS. No difference in treatment effectiveness was shown between the two groups, and adverse effects were comparable. This was the largest randomized trial ever undertaken in FSGS, but it was unfortunately underpowered to show clinically relevant differences in response rates. This shortcoming, along with particularities of the study population and outcome measures, makes it challenging to draw definitive conclusions from the trial results. Despite these limitations, the trial does provide valuable insights into treatment strategies for FSGS and offers important lessons for planning future research.

  9. Impact of the ALMS and MAINTAIN trials on the management of lupus nephritis.

    Science.gov (United States)

    Morris, Heather K; Canetta, Pietro A; Appel, Gerald B

    2013-06-01

    Current treatment of lupus nephritis consists of both induction and maintenance therapy, with the latter being designed to consolidate remissions and prevent relapses. Long-term maintenance treatment with intravenous cyclophosphamide was effective but associated with considerable toxicity. A small but well-designed controlled trial found that for post-induction maintenance therapy, both oral mycophenolate mofetil (MMF) and oral azathioprine were superior in efficacy and had reduced toxicity than a regimen of continued every third month intravenous cyclophosphamide. Although these oral agents were rapidly accepted and utilized as maintenance medications, their usage was based on scant evidence and there were no comparisons between the two. Recently, two relatively large, randomized, well-controlled, multicenter trials dealing with maintenance therapy for severe lupus nephritis have been completed. The Aspreva Lupus Management Study (ALMS) maintenance and MAINTAIN nephritis trials provide important information regarding the comparative efficacy and safety of MMF and azathioprine as maintenance therapies, as well as information on the effect of dosage and duration of treatment with these agents.

  10. New-Onset Diabetes Mellitus After Transplantation in a Cynomolgus Macaque (Macaca fasicularis).

    Science.gov (United States)

    Matthews, Kristin A; Tonsho, Makoto; Madsen, Joren C

    2015-08-01

    A 5.5-y-old intact male cynomolgus macaque (Macaca fasicularis) presented with inappetence and weight loss 57 d after heterotopic heart and thymus transplantation while receiving an immunosuppressant regimen consisting of tacrolimus, mycophenolate mofetil, and methylprednisolone to prevent graft rejection. A serum chemistry panel, a glycated hemoglobin test, and urinalysis performed at presentation revealed elevated blood glucose and glycated hemoglobin (HbA1c) levels (727 mg/dL and 10.1%, respectively), glucosuria, and ketonuria. Diabetes mellitus was diagnosed, and insulin therapy was initiated immediately. The macaque was weaned off the immunosuppressive therapy as his clinical condition improved and stabilized. Approximately 74 d after discontinuation of the immunosuppressants, the blood glucose normalized, and the insulin therapy was stopped. The animal's blood glucose and HbA1c values have remained within normal limits since this time. We suspect that our macaque experienced new-onset diabetes mellitus after transplantation, a condition that is commonly observed in human transplant patients but not well described in NHP. To our knowledge, this report represents the first documented case of new-onset diabetes mellitus after transplantation in a cynomolgus macaque.

  11. Pediatric Renal Transplantation in a Highly Sensitised Child—8 Years On

    Directory of Open Access Journals (Sweden)

    Catherine Quinlan

    2011-01-01

    Full Text Available Highly sensitised children have markedly reduced chances of receiving a successful deceased donor renal transplant, increased risk of rejection, and decreased graft survival. There is limited experience with the long-term followup of children who have undergone desensitization. Following 2 failed transplants, our patient was highly sensitised. She had some immunological response to intravenous immunoglobulin (IVIg but this was not sustained. We developed a protocol involving sequential therapies with rituximab, IVIg, and plasma exchange. Immunosuppressant therapy at transplantation consisted of basiliximab, tacrolimus, mycophenolate mofetil, and steroids. At the time of transplantation, historical crossmatch was ignored. Current CDC crossmatch was negative, but T and B cell flow crossmatch was positive, due to donor-specific HLA Class I antibodies. Further plasma exchange and immunoglobulin therapy were given pre- and postoperatively. Our patient received a deceased donor-kidney-bearing HLA antigens to which she originally had antibodies, which would have precluded transplant. The graft kidney continues to function well 8 years posttransplant.

  12. HLA antibody-incompatible kidney transplantation between jehovah's witnesses--a case report.

    Science.gov (United States)

    Greenberg, A; Macphee, I; Popoola, J; Sage, D; Iqbal, R; Fossati, N; Heap, S; Morsy, M; Kessaris, N

    2013-06-01

    Desensitization before HLA antibody-incompatible (HLAi) transplantation involves nonspecific apheresis of HLA antibodies. Clotting factors and albumin are also removed and have to be replaced. This makes transplantation difficult because it increases the risk of bleeding. Such risk is further compounded when certain blood products are refused on religious grounds. We present a case of successful HLAi transplantation in a Jehovah's Witness across a positive-flow cytometric HLA crossmatch from a live donor who was also a Jehovah's Witness. This was achieved by giving rituximab 1 month before transplantation and starting prednisolone, tacrolimus, and mycophenolate mofetil 10 days before surgery. In preparation, the patient also underwent 4 sessions of double-filtration plasma exchange each followed by low-dose intravenous immunoglobulin. The night before transplantation, the fibrinogen was low, requiring 2 pools of cryoprecipitate. The organ was retrieved through laparoscopic hand-assisted retroperitoneoscopic nephrectomy and transplanted into the recipient with no complications. In addition, the patient received basiliximab during surgery. Sixteen months after transplantation the serum creatinine was 70 μmol/L (0.79 mg/dL) and there were no rejection episodes. To our knowledge this is the world's first live-related kidney transplant across the HLAi barrier between 2 Jehovah's Witnesses. This case may allow further HLAi transplants to be carried out in Jehovah's Witnesses in the future around the world. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Autoimmune hepatitis in children: what is different from adult AIH?

    Science.gov (United States)

    Mieli-Vergani, Giorgina; Vergani, Diego

    2009-08-01

    Autoimmune hepatitis (AIH) is characterized by inflammatory liver histology, circulating non-organ-specific autoantibodies, and increased levels of immunoglobulin (Ig) G in the absence of a known etiology. Two types of childhood AIH are recognized according to seropositivity: smooth muscle antibody (SMA) and/or antinuclear antibody (ANA), which is AIH type 1; and antibodies to liver-kidney microsome type 1 (anti-LKM1), which is AIH type 2. There is a female predominance in both. Autoimmune hepatitis type 2 presents more acutely, at a younger age, and commonly with IgA deficiency; however, duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in the two groups. Immunosuppressive treatment with steroids and azathioprine, which should be instituted promptly to avoid progression to cirrhosis, induces remission in 80% of cases. Relapses are common, often due to nonadherence. Drugs effective in refractory cases include cyclosporine and mycophenolate mofetil. Long-term treatment is usually required, with only some 20% of AIH type 1 patients able to discontinue therapy successfully. In childhood, sclerosing cholangitis with strong autoimmune features, including interface hepatitis and serological features identical to AIH type 1, is as prevalent as AIH, but it affects boys and girls equally. The differential diagnosis relies on cholangiographic studies. In autoimmune sclerosing cholangitis, liver parenchymal damage responds satisfactorily to immunosuppressive treatment, whereas bile duct disease tends to progress. Copyright Thieme Medical Publishers.

  14. Renal Infarction during Anticoagulant Therapy after Living Donor Liver Transplantation

    Directory of Open Access Journals (Sweden)

    Shinji Onda

    2018-04-01

    Full Text Available Introduction: Liver transplant recipients are at risk for complications of vascular thrombosis. The reconstructed hepatic artery and portal vein thrombosis potentially result in hepatic failure and graft loss. Renal infarction is a rare clinical condition, but in severe cases, it may lead to renal failure. We herein report a case of renal infarction after living donor liver transplantation (LDLT during anticoagulant therapy. Case Presentation: A 60-year-old woman with end-stage liver disease due to primary biliary cholangitis underwent LDLT with splenectomy. Postoperatively, tacrolimus, mycophenolate mofetil, and steroid were used for initial immunosuppression therapy. On postoperative day (POD 5, enhanced computed tomography (CT revealed splenic vein thrombosis, and anticoagulant therapy with heparin followed by warfarin was given. Follow-up enhanced CT on POD 20 incidentally demonstrated right renal infarction. The patient’s renal function was unchanged and the arterial flow was good, and the splenic vein thrombosis resolved. At 4 months postoperatively, warfarin was discontinued, but she developed recurrent splenic vein thrombosis 11 months later, and warfarin was resumed. As of 40 months after transplantation, she discontinued warfarin and remains well without recurrence of splenic vein thrombosis or renal infarction. Conclusion: Renal infarction is a rare complication of LDLT. In this case, renal infarction was incidentally diagnosed during anticoagulant therapy and was successfully treated.

  15. Desensitization with plasmapheresis and anti-Cd20 for ABO incompatible kidney transplantation from living donor: experience of a single center in Italy.

    Science.gov (United States)

    Silvestre, C; Furian, L; Marson, P; Tison, T; Valente, M; Marchini, F; Rossi, B; Bonfante, L; Valerio, F; Cozzi, E; Rigotti, P

    2014-09-01

    Blood group incompatibility in kidney transplants from a living donor can be successfully overcome by using various desensitization protocols: intravenous immunoglobulin, plasmapheresis (PP), immunoadsorption, and double filtration PP. From July 2010 to October 2013, we performed 10 ABO incompatible kidney transplantation (KT) procedures from a living donor. The desensitization protocol was based on rituximab and PP+cytomegalovirus immune globulin. All patients received induction with basiliximab, except 1 case treated with Thymoglobuline® (ATG) for the simultaneous presence of donor-specific antibody. Tacrolimus and mycophenolate mofetil were initiated at the time of desensitization and continued after the transplant. After a mean follow-up of 11.6±10.4 months, all patients are alive with a functioning graft. The mean serum creatinine concentration at 1 month, 3 months, 6 months, and 1 year was 1.48±0.29, 1.47±0.18, 1.47±0.27, and 1.5±0.27 mg/dl. Three episodes of acute cellular rejection occurred in 2 patients. There was only 1 case of BK virus infection, treated with reduction of immunosuppressive therapy. The protocol biopsy specimens at 1, 3, and 6 months were C4d positive in the absence of acute rejection. Desensitization with rituximab, PP, and anti-cytomegalovirus immune globulin allowed us to perform transplants from living donors to ABO incompatible recipients with excellent results and reduced costs. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Immune Desensitization Allows Pediatric Blood Group Incompatible Kidney Transplantation.

    Science.gov (United States)

    Stojanovic, Jelena; Adamusiak, Anna; Kessaris, Nicos; Chandak, Pankaj; Ahmed, Zubir; Sebire, Neil J; Walsh, Grainne; Jones, Helen E; Marks, Stephen D; Mamode, Nizam

    2017-06-01

    Blood group incompatible transplantation (ABOi) in children is rare as pretransplant conditioning remains challenging and concerns persist about the potential increased risk of rejection. We describe the results of 11 ABOi pediatric renal transplant recipients in the 2 largest centers in the United Kingdom, sharing the same tailored desensitization protocol. Patients with pretransplant titers of 1 or more in 8 received rituximab 1 month before transplant; tacrolimus and mycophenolate mofetil were started 1 week before surgery. Antibody removal was performed to reduce titers to 1 or less in 8 on the day of the operation. No routine postoperative antibody removal was performed. Death-censored graft survival at last follow-up was 100% in the ABOi and 98% in 50 compatible pediatric transplants. One patient developed grade 2A rejection successfully treated with antithymocyte globulin. Another patient had a titer rise of 2 dilutions treated with 1 immunoadsorption session. There was no histological evidence of rejection in the other 9 patients. One patient developed cytomegalovirus and BK and 2 others EBV and BK viremia. Tailored desensitization in pediatric blood group incompatible kidney transplantation results in excellent outcomes with graft survival and rejection rates comparable with compatible transplants.

  17. Panel-reactive antibody levels and renal transplantation rates in sensitized patients after desensitization and human leucocyte antigen amino acid residue matching.

    Science.gov (United States)

    Shang, Wenjun; Dong, Laidong; Feng, Guiwen; Wang, Yue; Pang, Xinlu; Li, Jinfeng; Liu, Lei; Zhang, Weihong

    2013-08-01

    To determine whether a new desensitization protocol (mycophenolate mofetil [MMF], plasmapheresis and antithymocyte globulin [ATG], complemented with human leucocyte antigen [HLA] amino acid residue matching) could reduce panel-reactive antibody (PRA) levels in sensitized patients, to facilitate successful renal transplantation. Patients awaiting transplantation with PRA levels >10% received treatment with MMF; those with PRA levels >30% were also treated with plasmapheresis. Patients whose PRA level was desensitization were eligible for transplantation. When a donor became available, traditional HLA matching and HLA amino acid residue matching were performed. All patients received ATG induction therapy postoperatively. Thirty-two sensitized patients were enrolled. Desensitization produced a significant decrease in PRA levels; 27 patients (84.4%) became eligible for transplantation and 26 (81.2%) subsequently underwent successful transplantation. Residue matching improved the proportion with a mismatch number of 0-1 from 7.7% to 65.4%, compared with traditional HLA matching. Postoperatively, all patients showed immediate graft function. Acute rejection occurred in three patients (11.5%) and infections in seven patients (25.9%); all were treated successfully. The combination of a desensitization protocol (MMF, plasmapheresis and ATG) and residue matching appears to be an effective strategy for sensitized patients awaiting renal transplantation.

  18. A 47-Year-Old Man With Fever, Dry Cough, and a Lung Mass After Redo Lung Transplantation.

    Science.gov (United States)

    Chaddha, Udit; Patil, Pradnya D; Omar, Ashraf; Walia, Rajat; Panchabhai, Tanmay S

    2018-06-01

    A 47-year-old man who was a redo double lung transplant recipient (cytomegalovirus [CMV] status: donor positive/recipient positive; Epstein-Barr virus status: donor positive/recipient positive) presented to the hospital with 1 week of generalized malaise, low-grade fevers, and dry cough. His redo lung transplantation was necessitated by bronchiolitis obliterans syndrome, and his previous lung transplantation 5 years earlier was for silicosis-related progressive massive fibrosis. He denied any difficulty breathing or chest pain. There was no history of GI or urinary symptoms, and the patient had no anorexia, weight loss, night sweats, sick contacts, or history of travel. He had a history of 1 earlier episode of CMV viremia that was treated with valganciclovir. His immunosuppressive regimen included tacrolimus, mycophenolate mofetil, and prednisone, and his infection prophylaxis included trimethoprim-sulfamethoxazole, itraconazole, and valganciclovir. Results of a chest radiograph 8 weeks earlier were normal. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  19. Anaemia and fever in Kidney transplant. The role of human parvovirus B19.

    Science.gov (United States)

    Parodis López, Yanet; Santana Estupiñán, Raquel; Marrero Robayna, Silvia; Gallego Samper, Roberto; Henríquez Palop, Fernando; Rivero Vera, José Carlos; Camacho Galán, Rafael; Pena López, María José; Sablón González, Nery; González Cabrera, Fayna; Oliva Dámaso, Elena; Vega Díaz, Nicanor; Rodríguez Pérez, José Carlos

    Infections remain an issue of particular relevance in renal transplant patients, particularly viral infections. Human parvovirus B19 infection causes severe refractory anaemia, pancytopenia and thrombotic microangiopathy. Its presence is recognized by analysing blood polymerase chain reaction (PCR) and by the discovery of typical giant proerythroblasts in the bone marrow. We report the case of a 65 year-old man with a history of deceased donor renal transplant in September 2014. At 38 days after the transplant, the patient presented progressive anaemia that was resistant to erythropoiesis-stimulating agents. At 64 days after transplant, hyperthermia occurred with progressive deterioration of the patient's general condition. The viral serology and the first blood PCR for human parvovirus B19 were both negative. At 4 months and 19 days after, a bone marrow biopsy was conducted, showing giant erythroblasts with nuclear viral inclusions that were compatible with parvovirus; a PCR in the tissue confirmed the diagnosis. A second blood PCR was positive for parvovirus. After treatment with intravenous immunoglobulin and the temporary discontinuation of mycophenolate mofetil, a complete remission of the disease occurred, although the blood PCR for parvovirus B19 remained positive, so monitoring is necessary for future likely recurrence. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  20. Persistent anemia in a kidney transplant recipient with parvovirus B19 infection

    Directory of Open Access Journals (Sweden)

    Abbas Pakkyara

    2017-01-01

    Full Text Available Anemia after kidney transplant is not uncommon. This paper reports a case of unexplained anemia in a kidney transplant recipient that persisted for more than two months, and that did not respond to recombinant human erythropoietin treatment but was successfully treated after diagnosing Parvovirus B19 (ParvoV B19 infection. A middle-aged male underwent living-unrelated kidney transplantation from Pakistan in April 2015. He was on triple immuno-suppression therapy consisting of prednisolone, tacrolimus, and mycophenolate mofetil. He presented with anemia which persisted for more than two months that did not improve with Darbepoetin alpha and required blood transfusions. A bone marrow biopsy demonstrated pure erythroid hypoplasia and occasional giant pronormoblasts characteristic of a ParvoV B19 infection. The serum was highly positive for ParvoV B19 DNA polymerase chain reaction. The anemia resolved completely three weeks after the administration of intravenous immunoglobulin. ParvoV B19 infection should be considered in the differential diagnosis of kidney transplant recipients who present with anemia associated with a low reticulocyte count.

  1. Clinical features of neuromuscular disorders in patients with N-type voltage-gated calcium channel antibodies

    Directory of Open Access Journals (Sweden)

    Andreas Totzeck

    2016-09-01

    Full Text Available Neuromuscular junction disorders affect the pre- or postsynaptic nerve to muscle transmission due to autoimmune antibodies. Members of the group like myasthenia gravis and Lambert-Eaton syndrome have pathophysiologically distinct characteristics. However, in practice, distinction may be difficult. We present a series of three patients with a myasthenic syndrome, dropped-head syndrome, bulbar and respiratory muscle weakness and positive testing for anti-N-type voltage-gated calcium channel antibodies. In two cases anti-acetylcholin receptor antibodies were elevated, anti-P/Q-type voltage-gated calcium channel antibodies were negative. All patients initially responded to pyridostigmine with a non-response in the course of the disease. While one patient recovered well after treatment with intravenous immunoglobulins, 3,4-diaminopyridine, steroids and later on immunosuppression with mycophenolate mofetil, a second died after restriction of treatment due to unfavorable cancer diagnosis, the third patient declined treatment. Although new antibodies causing neuromuscular disorders were discovered, clinical distinction has not yet been made. Our patients showed features of pre- and postsynaptic myasthenic syndrome as well as severe dropped-head syndrome and bulbar and axial muscle weakness, but only anti-N-type voltage-gated calcium channel antibodies were positive. When administered, one patient benefited from 3,4-diaminopyridine. We suggest that this overlap-syndrome should be considered especially in patients with assumed seronegative myasthenia gravis and lack of improvement under standard therapy.

  2. Regulatory dendritic cells for promotion of liver transplant operational tolerance: Rationale for a clinical trial and accompanying mechanistic studies.

    Science.gov (United States)

    Thomson, Angus W; Humar, Abhinav; Lakkis, Fadi G; Metes, Diana M

    2018-05-01

    Dendritic cells (DC) are rare, bone marrow (BM)-derived innate immune cells that critically maintain self-tolerance in the healthy steady-state. Regulatory DC (DCreg) with capacity to suppress allograft rejection and promote transplant tolerance in pre-clinical models can readily be generated from BM precursors or circulating blood monocytes. These DCreg enhance allograft survival via various mechanisms, including promotion of regulatory T cells. In non-human primates receiving minimal immunosuppressive drug therapy (IS), infusion of DCreg of donor origin, one week before transplant, safely prolongs renal allograft survival and selectively attenuates anti-donor CD8 + memory T cell responses in the early post-transplant period. Based on these observations, and in view of the critical need to reduce patient dependence on non-specific IS agents that predispose to cardiometabolic side effects and renal insufficiency, we will conduct a first-in-human safety and preliminary efficacy study of donor-derived DCreg infusion to achieve early (18 months post-transplant) complete IS withdrawal in low-risk, living donor liver transplant recipients receiving standard-of-care IS (mycophenolate mofetil, tacrolimus and steroids). We will test the hypothesis that, although donor-derived DCreg are short-lived, they will induce robust donor-specific T cell hyporesponsiveness. We will examine immunological mechanisms by sequential analysis of blood and tissue samples, incorporating cutting-edge technologies. Copyright © 2017 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  3. Vulvovaginal gingival lichen planus: report of two cases and review of literature.

    Science.gov (United States)

    Lucchese, A; Dolci, A; Minervini, G; Salerno, C; DI Stasio, D; Minervini, G; Laino, L; Silvestre, F; Serpico, R

    2016-01-01

    Oral Lichen Planus (OLP) is a chronic inflammatory disease of skin and mucous membranes. Approximately 20% of women with oral lichen planus develops lesions in the genital mucosa. In 1982, Pelisse described a special form of lichen planus (LP), which consists of a triad of symptoms: vulval, vaginal and gingival (VVG)-LP lesions. Aim of the present report is to report two new cases and review the international literature. Two cases of VVG-LP are reported and a review of recent literature is performed. The onset of erosive or ulcerative mouth lesions may precede or follow by months or even years the onset of vulvovaginal lesions. Vaginal agglutination is associated with the postmenopausal state in conjunction with a dermatologic condition. Intra-lesional corticosteroids have a role in localized chronic ulceration, while systemic therapies such as corticosteroids, azathioprine, mycophenolate mofetil, hydroxychloroquine, ciclosporin, methotrexate, retinoids, thalidomide and photo chemotherapy have been used in more severe cases with varying success. VVG-LP is rather a rare condition and has been documented in the literature mainly in the form of case reports. Lack of a precise diagnostic criteria of VVG-LP depends on the specialists.

  4. Paradoxical Reaction of Tuberculosis in a Heart Transplant Recipient During Antituberculosis Therapy: A Case Report.

    Science.gov (United States)

    Wakamiya, A; Seguchi, O; Shionoiri, A; Kumai, Y; Kuroda, K; Nakajima, S; Yanase, M; Matsuda, S; Wada, K; Matsumoto, Y; Fukushima, S; Fujita, T; Kobayashi, J; Fukushima, N

    2018-04-01

    Tuberculous paradoxical reactions (PRs) are excessive immune reactions occurring after antituberculosis (TB) treatment and are commonly observed in immunocompromised hosts such as patients infected with the human immunodeficiency virus. We recently encountered a 63-year-old male heart transplant recipient who developed tuberculous PR after treatment for miliary TB. The patient had been receiving immunosuppressive therapy with cyclosporine and mycophenolate mofetil for over 15 years. The diagnosis of miliary TB was made based on the presence of intermittent fever and fatigue; thus, anti-TB treatments (isoniazid, levofloxacin, ethambutol, and pyrazinamide) were started, which led to rapid defervescence and regression of the granular shadow and pleural effusion. However, a new persistent fever and confused state developed 1 month after the anti-TB therapy was started. After excluding possible etiologies of the patient's symptom, a PR was suspected, and anti-TB drugs were continued; corticosteroids were added as anti-inflammatory agents. After that, he has shown a favorable course with long-term anti-TB chemotherapy. A PR should always be considered when the patients' symptoms of tuberculosis re-exacerbate after an appropriate anti-TB therapy. A PR commonly occurs in patients with various immunologic conditions including heart transplant recipients. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Characterization of clinical and genetic risk factors associated with dyslipidemia after kidney transplantation.

    Science.gov (United States)

    Numakura, Kazuyuki; Kagaya, Hideaki; Yamamoto, Ryohei; Komine, Naoki; Saito, Mitsuru; Hiroshi, Tsuruta; Akihama, Susumu; Inoue, Takamitsu; Narita, Shintaro; Tsuchiya, Norihiko; Habuchi, Tomonori; Niioka, Takenori; Miura, Masatomo; Satoh, Shigeru

    2015-01-01

    We determined the prevalence of dyslipidemia in a Japanese cohort of renal allograft recipients and investigated clinical and genetic characteristics associated with having the disease. In total, 126 patients that received renal allograft transplants between February 2002 and August 2011 were studied, of which 44 recipients (34.9%) were diagnosed with dyslipidemia at 1 year after transplantation. Three clinical factors were associated with a risk of having dyslipidemia: a higher prevalence of disease observed among female than male patients (P = 0.021) and treatment with high mycophenolate mofetil (P = 0.012) and prednisolone (P = 0.023) doses per body weight at 28 days after transplantation. The genetic association between dyslipidemia and 60 previously described genetic polymorphisms in 38 putative disease-associated genes was analyzed. The frequency of dyslipidemia was significantly higher in patients with the glucocorticoid receptor (NR3C1) Bcl1 G allele than in those with the CC genotype (P = 0.001). A multivariate analysis revealed that the NR3C1 Bcl1 G allele was a significant risk factor for the prevalence of dyslipidemia (odds ratio = 4.6; 95% confidence interval = 1.8-12.2). These findings may aid in predicting a patient's risk of developing dyslipidemia.

  6. March 2015 pulmonary case of the month: sticks and stones may break my bronchi

    Directory of Open Access Journals (Sweden)

    Amer S

    2015-03-01

    Full Text Available No abstract available. Article truncated after 150 words. History of Present Illness: A 67-year-old woman presented to the emergency department with a chief complaint of persistent cough of 2 months duration, productive of yellow sputum. Her symptoms progressed to include dyspnea despite an outpatient course of antibiotics, bronchodilators, and corticosteroids. She denied fevers, chills, hemoptysis, or chest pain. PMH, FH, SH: She was on chronic immunosuppression secondary to a history of liver transplant due to non-alcoholic steatohepatitis and kidney transplant due to calcineurin toxicity. She denied any history of smoking, alcoholism or recreational drug use. Medications: Tacrolimus 3.5 mg bid, Mycophenolate mofetil 720 mg bid, Fluconazole 100 mg daily. Physical Examination: Vitals: Temperature 37.1°C, respiratory rate 18 breaths/min, heart rate 88 beats/min, blood pressure 130/76 mm Hg, SpO2 95% on room air. General: Elderly female in no apparent distress. Lungs: Scattered inspiratory and expiratory squeaks and pops bilaterally, louder in the left lower lobe. The rest of her ...

  7. Modified uterine allotransplantation and immunosuppression procedure in the sheep model.

    Directory of Open Access Journals (Sweden)

    Li Wei

    Full Text Available OBJECTIVE: To develop an orthotopic, allogeneic, uterine transplantation technique and an effective immunosuppressive protocol in the sheep model. METHODS: In this pilot study, 10 sexually mature ewes were subjected to laparotomy and total abdominal hysterectomy with oophorectomy to procure uterus allografts. The cold ischemic time was 60 min. End-to-end vascular anastomosis was performed using continuous, non-interlocking sutures. Complete tissue reperfusion was achieved in all animals within 30 s after the vascular re-anastomosis, without any evidence of arterial or venous thrombosis. The immunosuppressive protocol consisted of tacrolimus, mycophenolate mofetil and methylprednisolone tablets. Graft viability was assessed by transrectal ultrasonography and second-look laparotomy at 2 and 4 weeks, respectively. RESULTS: Viable uterine tissue and vascular patency were observed on transrectal ultrasonography and second-look laparotomy. Histological analysis of the graft tissue (performed in one ewe revealed normal tissue architecture with a very subtle inflammatory reaction but no edema or stasis. CONCLUSION: We have developed a modified procedure that allowed us to successfully perform orthotopic, allogeneic, uterine transplantation in sheep, whose uterine and vascular anatomy (apart from the bicornuate uterus is similar to the human anatomy, making the ovine model excellent for human uterine transplant research.

  8. Characterization of Clinical and Genetic Risk Factors Associated with Dyslipidemia after Kidney Transplantation

    Science.gov (United States)

    Numakura, Kazuyuki; Kagaya, Hideaki; Yamamoto, Ryohei; Komine, Naoki; Saito, Mitsuru; Hiroshi, Tsuruta; Akihama, Susumu; Narita, Shintaro; Tsuchiya, Norihiko; Habuchi, Tomonori; Niioka, Takenori; Miura, Masatomo; Satoh, Shigeru

    2015-01-01

    We determined the prevalence of dyslipidemia in a Japanese cohort of renal allograft recipients and investigated clinical and genetic characteristics associated with having the disease. In total, 126 patients that received renal allograft transplants between February 2002 and August 2011 were studied, of which 44 recipients (34.9%) were diagnosed with dyslipidemia at 1 year after transplantation. Three clinical factors were associated with a risk of having dyslipidemia: a higher prevalence of disease observed among female than male patients (P = 0.021) and treatment with high mycophenolate mofetil (P = 0.012) and prednisolone (P = 0.023) doses per body weight at 28 days after transplantation. The genetic association between dyslipidemia and 60 previously described genetic polymorphisms in 38 putative disease-associated genes was analyzed. The frequency of dyslipidemia was significantly higher in patients with the glucocorticoid receptor (NR3C1) Bcl1 G allele than in those with the CC genotype (P = 0.001). A multivariate analysis revealed that the NR3C1 Bcl1 G allele was a significant risk factor for the prevalence of dyslipidemia (odds ratio = 4.6; 95% confidence interval = 1.8–12.2). These findings may aid in predicting a patient's risk of developing dyslipidemia. PMID:25944971

  9. Randomized controlled trial of FTY720 versus MMF in de novo renal transplantation.

    Science.gov (United States)

    Tedesco-Silva, Helio; Pescovitz, Mark D; Cibrik, Diane; Rees, Michael A; Mulgaonkar, Shamkant; Kahan, Barry D; Gugliuzza, Kristene K; Rajagopalan, P R; Esmeraldo, Ronaldo de M; Lord, Hélène; Salvadori, Maurizio; Slade, Jennifer M

    2006-12-27

    Phase II trials of FTY720, a novel immunomodulator, have shown promise in preventing rejection with both standard and reduced cyclosporine exposure. This study was designed to confirm those findings. This one-year, multicenter, randomized, phase III study in 696 de novo renal transplant patients compared FTY720 5 mg plus reduced-dose cyclosporine (RDC) or FTY720 2.5 mg plus full-dose cyclosporine (FDC) with mycophenolate mofetil (MMF) plus FDC. All patients received concomitant corticosteroid therapy without antibody induction. The primary efficacy composite endpoint was the incidence of first treated biopsy-proven acute rejection (treated BPAR), graft loss, death or premature study discontinuation at month 12. FTY720 2.5 mg plus FDC was demonstrated to be non-inferior to MMF plus FDC as the primary efficacy endpoint (30.8% and 30.6%) was comparable. The FTY720 5 mg plus RDC treatment regimen was discontinued due to an increased incidence of acute rejection episodes (primary endpoint 43.3%). FTY720 was associated with significantly lower creatinine clearance with a mean difference at 12 months between FTY720 2.5 mg plus FDC and MMF plus FDC of 8 ml/min. While FTY720 2.5 mg plus FDC yielded similar efficacy to MMF plus FDC, the FTY720 5 mg plus RDC did not allow a 50% reduction in cyclosporine exposure. The associated lower creatinine clearance indicated that FTY720 combined with cyclosporine provided no benefit over standard care.

  10. Bone metabolism in renal transplant patients treated with cyclosporine or sirolimus.

    Science.gov (United States)

    Campistol, Josep M; Holt, David W; Epstein, Solomon; Gioud-Paquet, Martine; Rutault, Karine; Burke, James T

    2005-09-01

    Sirolimus is a new immunosuppressive agent used as treatment to prevent acute renal allograft rejection. One of the complications of renal transplantation and subsequent long-term immunosuppression is bone loss associated with osteoporosis and consequent fracture. Two open-label, randomized, phase 2 studies comparing sirolimus versus cyclosporine (CsA) included indices of bone metabolism as secondary end-points. Markers of bone turnover, serum osteocalcin and urinary N-telopeptides, were measured over a 1-year period in 115 patients receiving either CsA or sirolimus as a primary therapy in combination with azathioprine and glucocorticoids (study A) or mycophenolate mofetil (MMF) and glucocorticoids (study B). Urinary excretion of N-telopeptides and the concentrations of serum osteocalcin were consistently higher in the CsA-treated patients and significantly different at week 24 for N-telopeptides and at weeks 12, 24, and 52 for osteocalcin. In conclusion, future trials are warranted to test whether a sirolimus-based regimen conserves bone mineral density compared with a CsA-based regimen.

  11. Mycophenolate plus methylprednisolone versus methylprednisolone alone in active, moderate-to-severe Graves' orbitopathy (MINGO): a randomised, observer-masked, multicentre trial

    NARCIS (Netherlands)

    Kahaly, George J.; Riedl, Michaela; König, Jochem; Pitz, Susanne; Ponto, Katharina; Diana, Tanja; Kampmann, Elena; Kolbe, Elisa; Eckstein, Anja; Moeller, Lars C.; Führer, Dagmar; Salvi, Mario; Curro, Nicola; Campi, Irene; Covelli, Danila; Leo, Marenza; Marinò, Michele; Menconi, Francesca; Marcocci, Claudio; Bartalena, Luigi; Perros, Petros; Wiersinga, Wilmar M.; Ayvaz, Göksun; Baldeschi, Lelio; Boborides, Kostas; Boschi, Antonella; Brix, Thomas H.; Clarke, Lucy; Dayan, Colin; Daumerie, Chantal; Dickinson, A. Jane; Fichter, Nicole; Hegedüs, Laszlo; Konuk, Onur; Krassas, Gerassimos E.; Lane, Carol; Lazarus, John; Morris, Dan S.; Mourits, Maarten; Nardi, Marco; Neoh, Chris; Orgiazzi, Jacques; Pearce, Simon H. S.; von Arx, Georg; Zarkovic, Milos

    2018-01-01

    European guidelines recommend intravenous methylprednisolone as first-line treatment for active and severe Graves' orbitopathy; however, it is common for patients to have no response or have relapse after discontinuation of treatment. We aimed to compare the efficacy and safety of add-on

  12. Acute tubulointerstitial nephritis with severe renal impairment associated with multisystem IgG4-related disease.

    Science.gov (United States)

    Beltrame, Rafael Coimbra Ferreira; Friderichs, Maurício; Fior, Bárbara Rayanne; Schaefer, Pedro Guilherme; Thomé, Gustavo Gomes; Silva, Dirceu Reis da; Barros, Elvino José Guardão; Seligman, Renato; Veronese, Francisco Veríssimo

    2016-01-01

    The IgG4-related disease has a wide clinical spectrum where multiple organs can be affected, and the diagnosis depends on typical histopathological findings and an elevated IgG4 expression in plasma cells in the affected tissue. We describe the clinical presentation and evolution of a patient with acute tubulointerstitial nephritis, severe kidney failure and systemic manifestations such as lymphadenomegaly and chronic pancreatitis. The diagnosis was confirmed by the clinical picture and kidney and lymph node histopathology, in which immunohistochemistry of the lymphoid tissue showed policlonality and increased expression of IgG4, with a IgG4/total IgG ratio > 80%. The patient was treated with prednisone at a dose of 60 mg/day, followed by mycophenolate mofetil, and showed clinical and renal function improvement at 6 months of follow-up. The high index of suspicion of IgG4-related disease with multisystem involvement and the early treatment of this condition are essential to improve the prognosis of affected patients. Resumo A doença relacionada à IgG4 tem um espectro clínico amplo em que múltiplos órgãos podem ser afetados, e o diagnóstico depende de achados histopatológicos típicos e elevada expressão de IgG4 em plasmócitos no tecido afetado. Descrevemos o quadro clínico e a evolução de um paciente com nefrite túbulo-intersticial aguda, insuficiência renal grave e manifestações sistêmicas como linfoadenomegalias e pancreatite crônica. O diagnóstico foi confirmado pelas características clínicas e pela histopatologia renal e de linfonodo, na qual a imunohistoquímica mostrou tecido linfoide com policlonalidade e expressão aumentada de IgG4, com uma relação IgG4/IgG total > 80%. O paciente foi tratado com prednisona na dose de 60 mg/dia, seguido de micofenolato mofetil, e apresentou melhora clínica e da função renal depois de 6 meses de tratamento. O alto índice de suspeição da doença relacionada ao IgG4 com comprometimento multissist

  13. Deceased donor organ transplantation with expanded criteria donors: a single-center experience from India.

    Science.gov (United States)

    Goplani, K R; Firoz, A; Ramakrishana, P; Shah, P R; Gumber, M R; Patel, H V; Vanikar, A V; Trivedi, H L

    2010-01-01

    Deceased donor organ transplantation (DDOT) accounts for DKT) and 19 single (SKT). Fourteen donors had hypertension, a cerebrovascular accident as the cause of death, 9 had both, and 4 had diabetes. Mean donor age was 70.3 +/- 8.9 years. Decisions on the procedure were based upon frozen section biopsy in 13 of 21 donors. Mean DKT donor age was 76 +/- 9.7 years versu 64 +/- 5.7 years of SKT donors. The native kidney diseases were chronic glomerulonephritis (n = 14), diabetic nephropathy (n = 7), tubulointerstitial nephritis (n = 4) and polycystic kidney disease, focal segmental glomerulosclerosis, lupus nephritis and patchy cortical necrosis, (n = 1 each). Mean recipient age of DKT versus SKT was 43.5 versus 42.3 years. All recipients received rabbit anti-thymocyte globulin, followed by steroid, mycophenolate mofetil/calcinueurin inhibitor. Over a mean follow-up of 341 days, the mean serum creatinine (SCr) of 25/29 patients was 1.60 mg/dL (range, 1.0-2.6). The mean SCr of SKT patients was 1.59 +/- 0.63 mg/dL and of DKT, 1.62 +/- 0.48 mg/dL. Ten patients had delayed graft function and 11 had biopsy proven acute tubular necrosis. Seven (24%) patients had rejection (grade 3 Banff update '05, type IA; 4, type 2A); 6 responded to antirejection; 1 graft was lost at 7 months due to chronic rejection. Three (10.3%) patients were lost, 1 each due to AMI, sepsis, and CMV disease. In the circumstances of organ shortage, DDOT with expanded criteria donor is a feasible option.

  14. Oral Valganciclovir as a Preemptive Treatment for Cytomegalovirus (CMV Infection in CMV-Seropositive Liver Transplant Recipients.

    Directory of Open Access Journals (Sweden)

    Jong Man Kim

    Full Text Available Cytomegalovirus (CMV infections in liver transplant recipients are common and result in significant morbidity and mortality. Intravenous ganciclovir or oral valganciclovir are the standard treatment for CMV infection. The present study investigates the efficacy of oral valganciclovir in CMV infection as a preemptive treatment after liver transplantation.Between 2012 and 2013, 161 patients underwent liver transplantation at Samsung Medical Center. All patients received tacrolimus, steroids, and mycophenolate mofetil. Patients with CMV infection were administered oral valganciclovir (VGCV 900mg/day daily or intravenous ganciclovir (GCV 5mg/kg twice daily as preemptive treatment. Stable liver transplant recipients received VGCV.Eighty-three patients (51.6% received antiviral therapy as a preemptive treatment because of CMV infection. The model for end-stage liver disease (MELD score and the proportions of Child-Pugh class C, hepatorenal syndrome, and deceased donor liver transplantation in the CMV infection group were higher than in the no CMV infection group. Sixty-one patients received GCV and 22 patients received VGCV. The MELD scores in the GCV group were higher than in the VGCV group, but there were no statistical differences in the pretransplant variables between the two groups. AST, ALT, and total bilirubin levels in the GCV group were higher than in the VGCV group when CMV infection occurred. The incidences of recurrent CMV infection in the GCV and VGCV groups were 14.8% and 4.5%, respectively (P=0.277.Oral valganciclovir is feasible as a preemptive treatment for CMV infection in liver transplant recipients with stable graft function.

  15. ABO-incompatible kidney transplantation: first cases in Turkey.

    Science.gov (United States)

    Tuncer, M; Yücetin, L; Tekin, S; Demirbas, A

    2012-01-01

    ABO compatibility has been believed to be necessary in kidney transplantation (Ktx) to prevent acute antibody-mediated rejection. However, developments in immunosuppression and immunoadsorption techniques have overcome acute antibody-mediated rejection caused by ABO incompatibility. Herein, we have presented the first ABO-incompatible Ktx cases in Turkey. All recipients did not have an ABO-compatible donor but presented significant dialysis inadequacy due to vascular access problems. Five dialysis patients with blood groups O or B underwent kidney transplantation from living related donors of blood group type A1 or AB between march 23, 2007 and August 16, 2007. All patients received Rituximab (375 mg/m(2)) at 3-4 weeks before the Ktx. Additionally, we started tacrolimus (0.15 mg/kg), mycophenolate mofetil (2 × 1 g), and simvastatin (1 × 20 mg) 1 week before the operation. Immunoadsorption therapy employing a specific filter (Glycosorbs) to remove anti-A or anti-B antibodies was continued until the titers were 1/8 during the first postoperative week and >1/16 at the second postoperative week. We used 2 standard hemodialysis machines with a connection line to perform immunoabsorption and dialysis during the same session. Acute humoral and cellular rejection was not detected. During the follow-up 1 patient was lost due to a cardiovascular complication. Mean creatinine level was 1.1 ± 0.3 mg/dL. These first ABO-incompatible transplantation cases in Turkey suggest that this source may represent an effective approach to overcome the organ shortage. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Immunosuppressive treatment for nephrotic idiopathic membranous nephropathy: a meta-analysis based on Chinese adults.

    Directory of Open Access Journals (Sweden)

    Guoqiang Xie

    Full Text Available Idiopathic membranous nephropathy (IMN is the most common pathological type for nephrotic syndrome in adults in western countries and China. The benefits and harms of immunosuppressive treatment in IMN remain controversial.To assess the efficacy and safety of different immunosuppressive agents in the treatment of nephrotic syndrome caused by IMN.PubMed, EMBASE, Cochrane Library and wanfang, weipu, qinghuatongfang, were searched for relevant studies published before December 2011. Reference lists of nephrology textbooks, review articles were checked. A meta-analysis of randomized controlled trials (RCTs meeting the criteria was performed using Review Manager.17 studies were included, involving 696 patients. Calcineurin inhibitors had a better effect when compared to alkylating agents, on complete remission (RR 1.61, 95% CI 1.13, to 2.30 P = 0.008, partial or complete remission (effective (CR/PR, RR 1.29, 95% CI 1.09 to 1.52 P = 0.003, and fewer side effects. Among calcineurin inhibitors, tacrolimus (TAC was shown statistical significance in inducing more remissions. When compared to cyclophosphamide (CTX, leflunomide (LET showed no beneficial effect, mycophenolate mofetil (MMF showed significant beneficial on effectiveness (CR/PR, RR: 1.41, 95% CI 1.16 to 1.72 P = 0.0006 but not significant on complete remission (CR, RR: 1.38, 95% CI 0.89 to 2.13 P = 0.15.This analysis based on Chinese adults and short duration RCTs suggested calcineurin inhibitors, especially TAC, were more effective in proteinuria reduction in IMN with acceptable side effects. Long duration RCTs were needed to confirm the long-term effects of those agents in nephrotic IMN.

  17. Ocular findings after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Tabbara, Khalid F; Al-Ghamdi, Ahmad; Al-Mohareb, Fahad; Ayas, Mouhab; Chaudhri, Naeem; Al-Sharif, Fahad; Al-Zahrani, Hazzaa; Mohammed, Said Y; Nassar, Amr; Aljurf, Mahmoud

    2009-09-01

    To study the incidence, causes, and outcome of major ocular complications in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Retrospective, noncomparative, observational clinical study. The study included a total of 620 patients who underwent allogeneic HSCT in the period from 1997 to 2007 at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. Allogeneic HSCT. Patients with ocular complications were referred to the ophthalmology division for complete ophthalmologic examination, including visual acuity, tonometry, Schirmer test, biomicroscopy, and dilated ophthalmoscopy. Laboratory investigations were performed whenever indicated. The incidence and causes of major ocular complications after allogeneic HSCT were determined. Visual acuity at 1 year after allogeneic HSCT was recorded. Major ocular complications occurred in 80 (13%) of 620 patients who underwent allogeneic HSCT. There were 36 male patients (45%) and 44 female patients (55%) with a mean age of 29 years and an age range of 9 to 65 years. Prophylaxis for graft-versus-host disease (GVHD) consisted of cyclosporine and methotrexate in 69 patients, and cyclosporine, methotrexate and corticosteroids, or mycophenolate mofetil in 11 patients. The most frequently encountered ocular complications were chronic GVHD, dry eye syndrome without GVHD, corneal ulcers, cataract, glaucoma, cytomegalovirus retinitis, fungal endophthalmitis, and acquisition of allergic conjunctivitis from atopic donors. There was no correlation between the pattern of ocular complications and the transplanted stem cell source. Best-corrected visual acuity (BCVA) at 1 year after transplantation was less than 20/200 in 13 patients (16%), less than 20/50 in 17 patients (21%), and better than 20/50 in 50 patients (63%). Ocular complications are common in patients undergoing allogeneic HSCT. Early recognition and prompt treatment are important. The author(s) have no proprietary or commercial

  18. The clinical spectrum and therapeutic management of hypocomplementemic urticarial vasculitis: data from a French nationwide study of fifty-seven patients.

    Science.gov (United States)

    Jachiet, Marie; Flageul, Béatrice; Deroux, Alban; Le Quellec, Alain; Maurier, François; Cordoliani, Florence; Godmer, Pascal; Abasq, Claire; Astudillo, Leonardo; Belenotti, Pauline; Bessis, Didier; Bigot, Adrien; Doutre, Marie-Sylvie; Ebbo, Mikaël; Guichard, Isabelle; Hachulla, Eric; Héron, Emmanuel; Jeudy, Géraldine; Jourde-Chiche, Noémie; Jullien, Denis; Lavigne, Christian; Machet, Laurent; Macher, Marie-Alice; Martel, Clotilde; Melboucy-Belkhir, Sara; Morice, Cécile; Petit, Antoine; Simorre, Bernard; Zenone, Thierry; Bouillet, Laurence; Bagot, Martine; Frémeaux-Bacchi, Véronique; Guillevin, Loïc; Mouthon, Luc; Dupin, Nicolas; Aractingi, Selim; Terrier, Benjamin

    2015-02-01

    Hypocomplementemic urticarial vasculitis (HUV) is an uncommon vasculitis of unknown etiology that is rarely described in the literature. We undertook this study to analyze the clinical spectrum and the therapeutic management of patients with HUV. We conducted a French nationwide retrospective study that included 57 patients with chronic urticaria, histologic leukocytoclastic vasculitis, and hypocomplementemia. We assessed clinical and laboratory data and evaluated the patients' cutaneous and immunologic responses to therapy. We evaluated treatment efficacy by measuring the time to treatment failure. Urticarial lesions were typically more pruritic than painful and were associated with angioedema in 51% of patients, purpura in 35%, and livedo reticularis in 14%. Extracutaneous manifestations included constitutional symptoms (in 56% of patients) as well as musculoskeletal involvement (in 82%), ocular involvement (in 56%), pulmonary involvement (in 19%), gastrointestinal involvement (in 18%), and kidney involvement (in 14%). Patients with HUV typically presented with low C1q levels and normal C1 inhibitor levels, in association with anti-C1q antibodies in 55% of patients. Hydroxychloroquine or colchicine seemed to be as effective as corticosteroids as first-line therapy. In patients with relapsing and/or refractory disease, rates of cutaneous and immunologic response to therapy seemed to be higher with conventional immunosuppressive agents, in particular, azathioprine, mycophenolate mofetil, or cyclophosphamide, while a rituximab-based regimen tended to have higher efficacy. Finally, a cutaneous response to therapy was strongly associated with an immunologic response to therapy. HUV represents an uncommon systemic and relapsing vasculitis with various manifestations, mainly, musculoskeletal and ocular involvement associated with anti-C1q antibodies, which were found in approximately half of the patients. The best strategy for treating HUV has yet to be defined

  19. Pediatric renal transplant practices in India.

    Science.gov (United States)

    Sethi, Sidharth Kumar; Sinha, Rajiv; Rohatgi, Smriti; Kher, Vijay; Iyengar, Arpana; Bagga, Arvind

    2017-05-01

    Limited access to tertiary-level health care, limited trained pediatric nephrologists and transplant physicians, lack of facilities for dialysis, lack of an effective deceased donor program, non-affordability, and non-adherence to immunosuppressant drugs poses a major challenge to universal availability of pediatric transplantation in developing countries. We present the results of a survey which, to the best of our knowledge, is the first such published attempt at understanding the current state of pediatric renal transplantation in India. A designed questionnaire formulated by a group of pediatric nephrologists with the aim of understanding the current practice of pediatric renal transplantation was circulated to all adult and pediatric nephrologists of the country. Of 26 adult nephrologists who responded, 16 (61.5%) were involved in pediatric transplantation, and 10 of 15 (66.6%) pediatric nephrologists were involved in pediatric transplantation. Most of the centers doing transplants were private/trust institution with only three government institutions undertaking it. Induction therapy was varied among pediatric and adult nephrologists. There were only a few centers (n=5) in the country routinely doing >5 transplants per year. Preemptive transplants and protocol biopsies were a rarity. The results demonstrate lower incidence of undertaking pediatric transplants in children below 6 years, paucity of active cadaveric programs and lack of availability of trained pediatric nephrologists and staff. In contrast to these dissimilarities, the immunosuppressant use seems to be quite similar to Western registry data with majority favoring induction agent and triple immunosuppressant (steroid, mycophenolate mofetil and tacrolimus) for maintenance. The survey also identifies major concerns in availability of this service to all regions of India as well as to all economic segments. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. The role of klotho in systemic sclerosis

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    R. Talotta

    2017-12-01

    Full Text Available The aim was to evaluate the role of klotho in the pathogenesis of systemic sclerosis (SSc, through the measurement of its serum concentration in SSc patients compared to healthy controls, and to assess the association with cutaneous and visceral involvement. Blood samples obtained from both SSc patients and healthy controls were analysed by an ELISA assay for the detection of human klotho. SSc patients were globally evaluated for disease activity and assessed through the modified Rodnan’s Skin Score, Medsger’s scale, pulmonary function tests, 2D-echocardiography, nailfold capillaroscopy and laboratory tests. Our cohort consisted of 69 SSc patients (61 females, mean age 64.5±12.5 years, median disease duration 9.0 (IQR 8 years and 77 healthy controls (28 females, mean age 49.7±10.2 years. In the group of SSc patients, 19 (27.5% suffered from a diffuse form of SSc. All patients were receiving IV prostanoids, and some of them were concomitantly treated with immunosuppressive drugs (prednisone, hydroxychloroquine, mofetil mycophenolate, methotrexate, cyclosporin A and azathioprine. The median serum concentration of klotho was significantly lower in patients compared to controls (0.23 ng/mL vs 0.60 ng/mL; p<0.001. However, Spearman’s test showed no significant association between klotho serum levels and disease activity, concerning either clinical, laboratory or instrumental findings. Our data show a significant deficit of klotho in SSc patients although any significant association was detected between klotho serum concentration and the clinical, laboratory or instrumental features of the disease. However, due to the limits of the study, further investigations are required.

  1. Selective T-cell Ablation with Bismuth-213 Labeled Anti-TCR Alpha Beta as Nonmyeloablative Conditioning for Allogeneic Canine Marrow Transplantion

    International Nuclear Information System (INIS)

    Bethge, W. A.; Wilbur, D. Scott; Storb, R.; Hamlin, Donald K.; Santos, E. B.; Brechbiel, M. W.; Fisher, Darrell R.; Sandmaier, B. M.

    2003-01-01

    Two major immunological barriers, the host versus graft (HVG) and the graft versus host (GVH) reaction, must be overcome for successful allogeneic hematopoietic stem cell transplantation. T-cells are involved in these barriers in the major histocompatibility complex-identical settings. We hypothesized that selective ablation of T-cells using radioimmunotherapy, together with postgrafting immunosuppression, would ensure stable allogeneic engraftment. We developed a canine model of nonmyeloablative marrow transplantation in which host immune reactions are impaired by a single dose of 2 Gy total body irradiation (TBI), and where both GVH and residual HVG reactions are controlled by postgrafting immunosuppression with mycophenolate mofetil (MMF) and cyclosporine (CSP). We substituted the alpha-emitter bismuth-213 linked to a monoclonal antibody against TCR(alpha,beta)using the metal-binding chelate CHX-A-DTPA, for 2 Gy TBI. Biodistribution studies using a gamma-emitting indium-111-labeled anti-TCR mAb showed uptake primarily in blood, marrow, lymph nodes, spleen and liver. In a dosimetry study, 4 dogs were treated with 0.13-0.46 mg/kg TCR mAb labeled with 3.7-5.6 mCi/kg (137-207 MBq/kg) Bi-213. The treatment was administered in 6 injections on days -3 and -2 followed by transplantion of dog leukocyte antigen-identical marrow on day 0 and postgrafting immunosuppression with MMF and CSP. Therapy was well tolerated except for elevations of transaminases, which were transient in all but one dog. No other organ toxicities or signs of graft-versus-host-disease were noted. The dogs had prompt allogeneic hematopoietic engraftment and achieved stable mixed donor-host hematopoietic chimerism with donor contributions ranging from 5-55 % with >30 weeks follow up

  2. THE ROLE OF IgM-ENRICHED INTRAVENOUS IMMUNOGLOBULIN IN TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    Szabó Judit

    2014-04-01

    Full Text Available After organ transplantation, gamma globulin and intravenous immunoglobulin enriched with IgM are most frequently used in septic shock as early immune-support. If the explanted organ is infected, the transplantation, as a life-saving operation, can be performed if there is no systemic inflammation and the patient receives IgM enriched immunoglobulin prophylaxis during surgery. The period after transplantation can be divided into three parts from the infection point of view: the first month after transplantation, the first sixth months and the following six months. Infections within the first month are basically related to the surgical procedure. Because of the immunosuppressive therapy, the opportunistic and fungal infections are more common during the first sixth months. After this period, the occurrence and the type of infections are similar to that of the non-transplant population except for pulmonary infections. The latter is two to three times more frequent. This is explained by the secondary hypogammaglobulinaemia (lower blood levels of IgM and IgG which is caused by the steroids but most of mycophenolate mofetil by inhibition of the T and B lymphocyte proliferation. Septic shock develops with a continuing fall of IgM levels. Under these circumstances additional intravenous immunoglobulin therapy with IgM can be lifesaving. Besides, immunoglobulin concentrates with IgM may also be used in the case of viral infections without prophylaxis and/or without etiological therapy such as in the case of West Nile virus infection. As a result of the increase in antibiotic resistance, the application of immunotherapy, including immunoglobulins may become the mainstream in the treatment of septic shock.

  3. Solitary pancreas retransplant: Study of 22 cases

    Directory of Open Access Journals (Sweden)

    Tércio Genzini

    2006-03-01

    Full Text Available Objective: To present our experience with pancreas retransplantin patients previously submitted to simultaneous pancreas-kidneytransplant, pancreas after kidney transplant and pancreastransplant alone. Methods: Between January/1996 and December/2005, 330 pancreas transplants were performed: 308 primarytransplants and 22 (6% retransplants of solitary pancreas. Thefollowing variables were analyzed: patient age; time elapsedbetween the first and the second transplant; causes of loss of thefirst graft; technical characteristics of the transplant andretransplant and the criteria for selecting donors for retransplant.These clinical data were submitted to statistical analysis. Results:The mean age of patients was 34.3 years and the mean elapsedtime between the first and second transplant was 19.3 months.The causes of the first graft loss were venous (8; 35% and arterial(5; 23% thrombosis, chronic rejection (4; 18%, ischemia/reperfusion injury (2, reflux pancreatitis (1, primary non-function(1 and sepsis (1. A second transplant was performed in thesame iliac fossa in 16 patients (72%. Venous drainage wasperformed in the iliac vein in 16 patients (72%, in the inferior venacava in 5 patients (22% and in the portal vein in one patient. 6 allbladder drainage was the technique used in 18 (82% cases andenteric drainage, in 4 patients (18%. Immunosuppressive regimenapplied to all cases was quadruple therapy with antilymphocyteinduction, tacrolimus, mycophenolate mofetil and steroids. Therewas one early death due to sepsis. One-year patient and pancreasgraft survival rates for retransplants were, respectively, 95% and85%. There was no additional risk for removing the pancreas graftat retransplant. Conclusion: Pancreas retransplant was technicallyfeasible in all cases and results similar to those described in theliterature were found for primary pancreas transplant.

  4. Single-shot antithymocyte globulin (ATG) induction for pancreas/kidney transplantation: ATG-Fresenius versus Thymoglobulin.

    Science.gov (United States)

    Schulz, T; Papapostolou, G; Schenker, P; Kapischke, M

    2005-03-01

    Single-shot antithymocyte globulin (ATG) prior to reperfusion followed by tacrolimus (TAC), mycophenolate mofetil (MMF), and prednisolone (PRD) is an established induction therapy in simultaneous pancreas kidney transplant (SPK) recipients. We retrospectively analyzed 6-month data from 105 patients who received their first SPK. From January 1996 to December 2000, ATG-Fresenius was used. Since January 2001, Thymoglobulin has been administered. In the first group, 58 patients were treated with ATG-Fresenius (4-6 mg/kg body weight). In the second group, 47 patients received Thymoglobulin (1.5-2.5 mg/kg body weight). HLA-mismatch was comparable. After an observation period of 6 months, patients, kidney, and pancreas graft survival is 98.3%, 96.6%, and 93.1% in group I and 97.9%, 97.9%, and 85.1% in group II, respectively. In each group, one death with functioning graft (DWFG) was observed. Twenty (34.5%) acute rejection episodes (AR) were observed (18 patients) in group I. They were treated with steroids (n = 16) or steroids/OKT3 (n = 4). One kidney graft failure was observed due to rejection and one due to DWFG. Four pancreas grafts were lost (thrombosis, n = 2; AR, n = 1; DWFG, n = 1). In group II, 15 AR (31.9%) were seen in 12 patients and were treated with steroids (n = 12), steroids/ATG (n = 1), or steroids/OKT3 (n = 2). Seven pancreas (thrombosis, n = 5; rejection, n = 1; DWFG, n = 1) and one kidney (DWFG, n = 1) graft losses occurred. These data clearly establish that single-shot ATG prior to reperfusion, followed by TAC, MMF, and PRD results in a low incidence of AR (34.5% in group I and 31.9% in group II) after SPK. Only 6.9% (group I) and 6.4% (group II) of the patients received antibodies for rejection treatment.

  5. ATG-Fresenius or daclizumab induction therapy in immunologically high risk kidney recipients: a prospective randomized pilot trial.

    Science.gov (United States)

    Kim, Min Jeong; Tsinalis, Dimitrios; Franz, Stefan; Binet, Isabelle; Gürke, Lorenz; Mihatsch, Michael J; Steiger, Jürg; Thiel, Gilbert; Dickenmann, Michael

    2008-01-01

    Despite all the advantages in the immunosuppressive therapy, kidney transplantation in immunologically high risk patients remains a challenge. Ideally, an induction therapy should provide maximal graft protection, while adverse events rate and costs remain as low as possible. Immunologically high risk kidney recipients with CDC-PRA ł 25% within the last 3 years, a positive B-cell CDC-crossmatch or graft loss due to rejection within 3 years following a prior transplantation, were randomized 1:1 to receive ATG-Fresenius (ATG-F) (9 mg/kg day 0; 3 mg/kg day 1-4) or Daclizumab therapy (1 mg/kg day 0, 14, 28, 42, 56) in a pilot study. Additional immunosuppression consisted of cyclosporine, mycophenolate mofetil, and steroids. 11 patients were included in each group. The patient (90% in ATG-F; 100% in Daclizumab) and graft survival (censored for death) (100% in ATG-F; 90% in Daclizumab) and the mean creatinine concentration at 24 months (139+/-68 mol/l in ATG-F; 176+/-103 mol/l in Daclizumab) were similar in both groups. More severe graft rejections (3 vascular rejections in Daclizumab) and adverse events (5.3/patient in ATG-F; 6.7/patient in Daclizumab) were observed in the Daclizumab group. The costs for hospitalization/ day within 24 months were lower in ATG-F (2.32+/-3.51 USD vs. 12.25+/-9.75 USD; p=0.02) resulting in an average cost-difference of more than 10'435 USD /patient. In this pilot trial, both treatments were comparably successful regarding graft and patient outcome.

  6. Effect of a single intraoperative high-dose ATG-Fresenius on delayed graft function in donation after cardiac-death donor renal allograft recipients: a randomized study.

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    van den Hoogen, Martijn W F; Kho, Marcia M L; Abrahams, Alferso C; van Zuilen, Arjan D; Sanders, Jan-Stephan; van Dijk, Marja; Hilbrands, Luuk B; Weimar, Willem; Hoitsma, Andries J

    2013-04-01

    Reducing the incidence of delayed graft function after transplant with donation after cardiac death donor renal allografts would facilitate managing recipients during their first weeks after a transplant. To reduce this incidence, in most studies, induction therapy with depleting anti-T-lymphocyte antibodies is coupled with a reduction of the dosage of the calcineurin inhibitor. The separate effect of anti-T-cell therapy on the incidence and duration of delayed graft function is therefore difficult to assess. We performed a randomized study to evaluate the effect of a single intraoperative high-dose of anti-T-lymphocyte immunoglobulin (ATG)-Fresenius (9 mg/kg body weight) on the incidence of delayed graft function. Eligible adult recipients of a first donation after cardiac death donor renal allograft were randomly assigned to ATG-Fresenius or no induction therapy. Maintenance immunosuppression consisted of tacrolimus, in an unadjusted dose, mycophenolate mofetil, and steroids. The study was prematurely terminated because of a lower-than-anticipated inclusion rate. Baseline characteristics were comparable in the ATG-Fresenius group (n=28) and the control group (n=24). Twenty-two patients in the ATG-Fresenius group (79%) had delayed graft function, compared with 13 in the control group (54%; P = .06). Allograft and patient survival were comparable in both groups. Serious adverse events occurred more frequently in the ATG-Fresenius group than they did in the control group (57% vs 29%; P Fresenius in donation after cardiac death donor renal allograft recipients, followed by triple immunosuppression with an unadjusted tacrolimus dose, seems ineffective to reduce the incidence of delayed graft function. Moreover, this was associated with a higher rate of serious adverse events (EudraCT-number, 2007-000210-36.).

  7. Update on the use of systemic biologic agents in the treatment of noninfectious uveitis

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    Pasadhika, Sirichai; Rosenbaum, James T

    2014-01-01

    Uveitis is one of the leading causes of blindness worldwide. Noninfectious uveitis may be associated with other systemic conditions, such as human leukocyte antigen B27-related spondyloarthropathies, inflammatory bowel disease, juvenile idiopathic arthritis, Behçet’s disease, and sarcoidosis. Conventional therapy with corticosteroids and immunosuppressive agents (such as methotrexate, azathioprine, mycophenolate mofetil, and cyclosporine) may not be sufficient to control ocular inflammation or prevent non-ophthalmic complications in refractory patients. Off-label use of biologic response modifiers has been studied as primary and secondary therapeutic agents. They are very useful when conventional immunosuppressive therapy has failed or has been poorly tolerated, or to treat concomitant ophthalmic and systemic inflammation that might benefit from these medications. Biologic therapy, primarily infliximab, and adalimumab, have been shown to be rapidly effective for the treatment of various subtypes of refractory uveitis and retinal vasculitis, especially Behçet’s disease-related eye conditions and the uveitis associated with juvenile idiopathic arthritis. Other agents such as golimumab, abatacept, canakinumab, gevokizumab, tocilizumab, and alemtuzumab may have great future promise for the treatment of uveitis. It has been shown that with proper monitoring, biologic therapy can significantly improve quality of life in patients with uveitis, particularly those with concurrent systemic symptoms. However, given high cost as well as the limited long-term safety data, we do not routinely recommend biologics as first-line therapy for noninfectious uveitis in most patients. These agents should be used with caution by experienced clinicians. The present work aims to provide a broad and updated review of the current and in-development systemic biologic agents for the treatment of noninfectious uveitis. PMID:24600203

  8. Update on the use of systemic biologic agents in the treatment of noninfectious uveitis

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    Pasadhika S

    2014-02-01

    Full Text Available Sirichai Pasadhika,1 James T Rosenbaum2 1Department of Ophthalmology, Southern Arizona Veterans Administration Health Care System, Tucson, AZ, USA; 2Legacy Devers Eye Institute, Portland, OR, USA Abstract: Uveitis is one of the leading causes of blindness worldwide. Noninfectious uveitis may be associated with other systemic conditions, such as human leukocyte antigen B27-related spondyloarthropathies, inflammatory bowel disease, juvenile idiopathic arthritis, Behçet's disease, and sarcoidosis. Conventional therapy with corticosteroids and immunosuppressive agents (such as methotrexate, azathioprine, mycophenolate mofetil, and cyclosporine may not be sufficient to control ocular inflammation or prevent non-ophthalmic complications in refractory patients. Off-label use of biologic response modifiers has been studied as primary and secondary therapeutic agents. They are very useful when conventional immunosuppressive therapy has failed or has been poorly tolerated, or to treat concomitant ophthalmic and systemic inflammation that might benefit from these medications. Biologic therapy, primarily infliximab, and adalimumab, have been shown to be rapidly effective for the treatment of various subtypes of refractory uveitis and retinal vasculitis, especially Behçet's disease-related eye conditions and the uveitis associated with juvenile idiopathic arthritis. Other agents such as golimumab, abatacept, canakinumab, gevokizumab, tocilizumab, and alemtuzumab may have great future promise for the treatment of uveitis. It has been shown that with proper monitoring, biologic therapy can significantly improve quality of life in patients with uveitis, particularly those with concurrent systemic symptoms. However, given high cost as well as the limited long-term safety data, we do not routinely recommend biologics as first-line therapy for noninfectious uveitis in most patients. These agents should be used with caution by experienced clinicians. The present

  9. Management of autoimmune hemolytic anemia in children and adolescents: A single center experience

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    Nazan Sarper

    2011-09-01

    Full Text Available Objective: To present and discuss the treatment of autoimmune hemolytic anemia (AIHA. Materials and Methods: The medical records of all patients (n=19 diagnosed in a tertiary hematology center between 1999 and 2010 were retrospectively reviewed.Results: Median age at diagnosis of AIHA was 5 years (range: 4 months-17 years. In all, 13 patients had primary (idiopathic AIHA, whereas 2 had primary Evans Syndrome (ES, 2 had autoimmune lymphoproliferative syndrome (ALPS+ES, and 1 had Wiskott-Aldrich syndrome (WAS+AIHA. Among the 13 primary idiopathic AIHA patients, 9 recovered following a 4-8-week course of prednisolone treatment without relapses, whereas 3 patients required a longer course of prednisolone. One AIHA patient that was very resistant to prednisolone recovered after cyclosporine A was added to the treatment. All patients with primary idiopathic AIHA were in remission for a median of 3 years (range: 4 months-10 years at the time this manuscript was written. Among the patients with primary ES, 2 had relapses similar to the ALPS patients. Splenectomy was performed in 1 primary ES patient, who at the time this report was written was also in remission. One ALPS patient required the addition of mycophenolate mofetil due to prednisolone resistance. The WAS patient was treatment resistant and died due to septicemia.Conclusions: Primary AIHA in pediatric patients generally has an acute onset and good response to corticosteroids. Primary or secondary ES has a chronic or relapsing course, and treatment may require other immunosuppressive agents in addition to corticosteroids. Complications of splenectomy must not be underestimated in patients with underlying immunodeficiency. AIHA often causes considerable morbidity and mortality in WAS.

  10. Early and late humoral rejection: a clinicopathologic entity in two times.

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    Péfaur, J; Díaz, P; Panace, R; Salinas, P; Fiabane, A; Quinteros, N; Chea, R; Naranjo, E; Wurgaft, A; Beltran, E; Elgueta, S; Wegmann, M E; Gajardo, J G; Contreras, L

    2008-11-01

    Humoral rejection is an important cause of early and late graft loss. The late variant is difficult to diagnose and treat. There is a close correlation between sclerosing nephropathy and anti-HLA antibodies. We analyzed 113 renal allograft recipients between August 2004 and April 2007. Acute humoral rejection was defined as acute graft dysfunction in presence of donor-specific antibodies (DSA) detected by flow panel reactive antibodies (PRA) and/or C4d positive pericapilary tubules (PTC) detected histopathologically by immunofluorescent or immunoperoxidase at less than 3 months postransplantation. Late humoral rejection was defined as dysfunction occurring after 3 months postransplantation with histopathologic glomerulopathy or vasculopathy and positive C4d PTC. We included all patients who were diagnosed with early or late graft dysfunction and underwent biopsy, all of which were examined for C4d. Four patients had acute humoral rejection treated with IVIG or plasmapheresis. The patient and graft survivals were 100% and serum creatinine averaged 1.7 mg/dL. Three recipients experienced late humoral rejection at 3 to 10 years posttransplantation All received high-dose IVIG; one also was treated with thymoglobulin. Immunosuppression was switched to tacrolimus, mycophenolate mofetil, and steroids. Only one patient recovered renal function; the others returned to dialysis. Among seven patients only one had an actual PRA (>20%) and three showed 10% to 20%. However, six had a positive historical PRA of 10% to 50%. In conclusion, Recognition of acute humoral rejection has contributed to graft rescue by controlling alloantibody production through new specific immunosuppressive therapies in contrast with the clinical response to acute therapy, treatment of a chronic entity has shown poor outcomes, probably because antibody mediated chronic graft damage is already present when the late diagnosis is established by biopsy.

  11. Pregnancy after renal transplantation: Effects on mother, child, and renal graft function

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    Siham El Houssni

    2016-01-01

    Full Text Available The aim of this study was to report our experience of pregnancy in renal transplant (RT patients and its medium and long-term effects on the renal graft as well as the maternal fetal complications. We studied 21 pregnancies in 12 RT patients with mean age of 29.9 ± 5.3 years. The mean duration of RT to 1 st pregnancy was 42 (21-68.5 months and the median follow-up period was 112.5 (138-165 months. The pregnancy was planned in 28.6% of the cases. At the time of the diagnosis of the pregnancy, all the patients were maintained on corticosteroids and cyclosporine, 14.3% of the patients were on mycophenolate mofetil, and 71.4% of the patients were on azathioprine. The high blood pressure was present before the pregnancy in 33.3% of the patients. During pregnancy, proteinuria appeared in 20% of the cases, urinary tract infection in 33.3%, and preeclampsia in 5%. Anemia was present in all the patients during pregnancy. The doses of cyclosporine were increased during pregnancy. The mean term of delivery was 37 ± 2 weeks. Premature delivery was observed in 19% of the cases, fetal death in utero in 10%, and abortion in 15%. The number of living children was 16, with a mean birth weight of 3014 ± 515 g; the weight was lower than 2500 g in three (15% cases. In the long-term follow-up, we noticed two cases of acute rejection related to patients′ noncompliance, and four cases of chronic allograft nephropathy, without a switch to dialysis. We conclude that pregnancy in RT patients requires multidisciplinary care because of the increased risks of maternal and fetal complications. Each pregnancy needs to be planned; all parameters have to be studied and evaluated in order to allow for optimization of outcome and minimization of complications.

  12. Bortezomib-based treatment of acute antibody-mediated rejection: a case report.

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    Wang, Q; Li, X L; Xu, X G; Shi, B Y; Zhang, Z M; Li, Z L; Han, Y; Zhou, W Q; Chen, C Q; Cai, M; Zhang, X

    2015-12-22

    Antibody-mediated rejection (AMR) is an important factor affecting survival after renal transplantation. A highly selective proteasome inhibitor, bortezomib, clears activated plasma cells from the body and has important therapeutic effect on AMR. We investigated the effects of bortezomib on AMR in a patient after a second renal transplant. Biopsy confirmed the diagnosis of mixed cellular rejection and AMR. Bortezomib was administered on day 1 (1.3 mg/m(2)), day 4 (1.0 mg/m(2)), and day 8 (1.0 mg/m(2)). On the same days, 250 mg methylprednisolone was administered once, and cyclosporine dose (5 mg·kg(-1)·day(-1)) was reduced by 50%. Oral mycophenolate mofetil and steroid were withdrawn on day 1 of bortezomib treatment. Intermittent double-filtration plasmapheresis was also performed. We monitored parameters, including T lymphocyte subsets, CD139 and CD19 expression, panel reactive antibody (PRA), and serum creatinine concentration. At follow-up 6 months after bortezomib treatment, we observed: 1) serum creatinine stabilized at 130 μM from a peak level of 337 μM; 2) PRA decreased from a maximum of 66.7 to 0%; 3) blood plasma cell percentage rebounded after significantly decreasing following the first dose of bortezomib; 4) in renal allograft biopsy, immunohistochemical staining for C4d shifted from strongly positive to negative, and cellular rejection shifted from type IIA to borderline; and 5) adverse effects such as platelet suppression, hypotension, and grade 3 peripheral neuropathy emerged. Bortezomib effectively treated antibody-mediated renal transplantation rejection in this case study, but clinical trials with large sample sizes are still needed to explore clinical safety and tolerability.

  13. Association of Endothelial Nitric Oxide Synthase Gene Polymorphisms With Acute Rejection in Liver Transplant Recipients.

    Science.gov (United States)

    Azarpira, Negar; Namazi, Soha; Malahi, Sayan; Kazemi, Kourosh

    2016-06-01

    Polymorphisms of the endothelial nitric oxide synthase gene have been associated with altered endothelial nitric oxide synthase activity. The purpose of this study was to investigate the relation between endothelial nitric oxide synthase -786T/C and 894G/T polymorphism and their haplotypes on the occurrence of acute rejection episodes in liver transplant recipients. We conducted a case control study in which 100 liver transplant recipients and 100 healthy controls were recruited from Shiraz Transplant Center. The patients used triple therapy including tacrolimus, mycophenolate mofetil, and prednisolone for immunosuppression maintenance. DNA was extracted from peripheral blood and endothelial nitric oxide synthase polymorphisms were determined by polymerase chain reaction and restriction fragment length polymorphism. Patients included 60 men and 40 women (mean age, 32.35 ± 10.2 y). There was a significant association of endothelial nitric oxide synthase 894G/T and acute rejection episode. The GT* gen-otype and acute rejection episodes had a significant association (odds ratio, 2.42; 95% confidence interval, 0.97-6.15; P = .03). The GG and GT* genotype and T* allele frequency were significantly different between patients and control subjects (P = .001). Haplotype TT* was higher in recipients than control subjects (odds ratio, 2.17; 95% confidence interval, 1.12-4.25; P = .01). Haplotype TG was higher in the control group (odds ratio, 0.62; 95% confidence interval, 0.40-0.96; P = .02). Our results suggest a relation between different endothelial nitric oxide synthase geno-types and risk of acute rejection episodes. However, further study is necessary to determine genetic susceptibility for transplant patients.

  14. Detrimental effects of rat mesenchymal stromal cell pre-treatment in a model of acute kidney rejection

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    Martina eSeifert

    2012-07-01

    Full Text Available Mesenchymal stromal cells (MSC have shown immunomodulatory and tissue repair potential including partial tolerance induction by pre-treatment of donor-specific cells in a rat heart transplantation model. Very recently, we could show that autologous MSC attenuated ischemia reperfusion injury in a highly mismatched donor-recipient rat kidney transplant model. Therefore, we investigated donor-specific MSC pre-treatment in this rat kidney transplantation model to study whether graft function could be improved, or if tolerance could be induced.Donor- and recipient-type MSC or PBS as a control were injected i.v. four days before kidney transplantation. Mycophenolate mofetil (MMF immunosuppression (20 mg/kg body weight was applied for 7 days. Kidney grafts and spleens were harvested between days 8-10 and analyzed by quantitative RT-PCR and immunohistology. In addition, creatinine levels in the blood were measured and serum was screened for the presence of donor-specific antibodies.Surprisingly, application of both donor- and recipient-specific MSC resulted in enhanced humoral immune responses verified by intragraft B cell infiltration and complement factor C4d deposits. Moreover, signs of inflammation and rejection were generally enhanced in both MSC-treated groups relative to PBS control group. Additionally, pre-treatment with donor-specific MSC significantly enhanced the level of donor-specific antibody formation when compared with PBS- or recipient-MSC-treated groups. Pre-treatment with both MSC types resulted in a higher degree of kidney cortex tissue damage and elevated creatinine levels at the time point of rejection. Thus, MSC pre-sensitization in this model impairs the allograft outcome.Our data from this pre-clinical kidney transplantation model indicate that pre-operative MSC administration may not be optimal in kidney transplantation and caution must be exerted before moving forward with clinical studies in order to avoid adverse effects.

  15. Cellular islet autoimmunity associates with clinical outcome of islet cell transplantation.

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    Volkert A L Huurman

    2008-06-01

    Full Text Available Islet cell transplantation can cure type 1 diabetes (T1D, but only a minority of recipients remains insulin-independent in the following years. We tested the hypothesis that allograft rejection and recurrent autoimmunity contribute to this progressive loss of islet allograft function.Twenty-one T1D patients received cultured islet cell grafts prepared from multiple donors and transplanted under anti-thymocyte globulin (ATG induction and tacrolimus plus mycophenolate mofetil (MMF maintenance immunosuppression. Immunity against auto- and alloantigens was measured before and during one year after transplantation. Cellular auto- and alloreactivity was assessed by lymphocyte stimulation tests against autoantigens and cytotoxic T lymphocyte precursor assays, respectively. Humoral reactivity was measured by auto- and alloantibodies. Clinical outcome parameters--including time until insulin independence, insulin independence at one year, and C-peptide levels over one year--remained blinded until their correlation with immunological parameters. All patients showed significant improvement of metabolic control and 13 out of 21 became insulin-independent. Multivariate analyses showed that presence of cellular autoimmunity before and after transplantation is associated with delayed insulin-independence (p = 0.001 and p = 0.01, respectively and lower circulating C-peptide levels during the first year after transplantation (p = 0.002 and p = 0.02, respectively. Seven out of eight patients without pre-existent T-cell autoreactivity became insulin-independent, versus none of the four patients reactive to both islet autoantigens GAD and IA-2 before transplantation. Autoantibody levels and cellular alloreactivity had no significant association with outcome.In this cohort study, cellular islet-specific autoimmunity associates with clinical outcome of islet cell transplantation under ATG-tacrolimus-MMF immunosuppression. Tailored immunotherapy targeting cellular

  16. 4-Pyridone-3-carboxamide-1-β-d-ribonucleoside Triphosphate (4PyTP, a Novel NAD+ Metabolite Accumulating in Erythrocytes of Uremic Children: A Biomarker for a Toxic NAD+ Analogue in Other Tissues?

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    Elizabeth A. Carrey

    2011-06-01

    Full Text Available We have identified a novel nucleotide, 4-pyridone 3/5-carboxamide ribonucleoside triphosphate (4PyTP, which accumulates in human erythrocytes during renal failure. Using plasma and erythrocyte extracts obtained from children with chronic renal failure we show that the concentration of 4PyTP is increased, as well as other soluble NAD+ metabolites (nicotinamide, N1-methylnicotinamide and 4Py-riboside and the major nicotinamide metabolite N1-methyl-2-pyridone-5-carboxamide (2PY, with increasing degrees of renal failure. We noted that 2PY concentration was highest in the plasma of haemodialysis patients, while 4PyTP was highest in erythrocytes of children undergoing peritoneal dialysis: its concentration correlated closely with 4Py-riboside, an authentic precursor of 4PyTP, in the plasma. In the dialysis patients, GTP concentration was elevated: similar accumulation was noted previously, as a paradoxical effect in erythrocytes during treatment with immunosuppressants such as ribavirin and mycophenolate mofetil, which deplete GTP through inhibition of IMP dehydrogenase in nucleated cells such as lymphocytes. We predict that 4Py-riboside and 4Py-nucleotides bind to this enzyme and alter its activity. The enzymes that regenerate NAD+ from nicotinamide riboside also convert the drugs tiazofurin and benzamide riboside into NAD+ analogues that inhibit IMP dehydrogenase more effectively than the related ribosides: we therefore propose that the accumulation of 4PyTP in erythrocytes during renal failure is a marker for the accumulation of a related toxic NAD+ analogue that inhibits IMP dehydrogenase in other cells.

  17. Multicenter Retrospective Analysis of the Effectiveness and Safety of Rituximab in Korean Patients with Refractory Systemic Lupus Erythematosus

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    So-Young Bang

    2012-01-01

    Full Text Available Objective. Although two recent randomized placebo-controlled trials of rituximab (RTX failed to demonstrate efficacy in systemic lupus erythematosus (SLE, clinicians continue to use off-label RTX for cases refractory to current treatments. We evaluated the effectiveness and safety of rituximab for patients with refractory SLE in Korea. Methods. We retrospectively analyzed multicenter patients treated with RTX in Korea. Results. 39 SLE patients treated with RTX were included in the following manner: lupus nephritis 43.6%, hematologic 33.3%, arthritis 7.8%, myositis 7.8%, and others 7.7%. All patients had responded poorly to at least one conventional immunosuppressive agent (mean 2.5 ± 1.1, cyclophosphamide 43.6%, mycophenolate mofetil 48.7%, and other drugs before RTX. Clinical improvements (complete or partial remission occurred in patients with renal disease, hematologic disease, arthritis, myositis, and other manifestations at 6 months after RTX. The SLEDAI score was significantly decreased from 10.8±7.1 at baseline to 6.7±4.0 at 6 months, 6.2±4.1 at 12 months, and 5.5±3.6 at 24 months after RTX (P<0.05. Among 28 clinical responders, 4 patients experienced a relapse of disease at 25±4 months. Infections were noted in 3 patients (7.7%. Conclusion. RTX could be an effective and relatively safe therapeutic option in patients with severe refractory SLE until novel B-cell depletion therapy is available.

  18. [Treatment of systemic lupus erythematosus: myths, certainties and doubts].

    Science.gov (United States)

    Ruiz-Irastorza, Guillermo; Danza, Alvaro; Khamashta, Munther

    2013-12-21

    Systemic lupus erythematosus (SLE) is a complex disease with different clinical forms of presentation, including a wide range of severity and organic involvement. Such circumstance, along with the fact of the uncommon nature of the disease and the absence of clinically representative response criteria, make it difficult to design controlled clinical trials in SLE patients. As a result, observational studies have a special relevance, being a source of valuable information of SLE prognosis and outcome as well as of the efficacy and adverse effects of the different therapies. Herein we update some of the main treatments used in SLE. Steroids may have more risks than benefits if used at high doses. New mechanisms of action have been described, supporting the use of lower doses, possibly with the same efficacy and less adverse effects. Intravenous pulses of cyclophosphamide still have a role in the treatment of proliferative lupus nephritis and other serious SLE manifestations. Mycophenolate mofetil has shown its efficacy both as induction and maintenance therapy of selected cases of lupus nephritis. Biological therapies have emerged as new promising options. Although clinical trials have not confirmed a clear superiority of rituximab in SLE, observational studies have shown good response rates in severe SLE manifestations or refractory forms. Belimumab has recently been added to the therapeutic armamentarium of SLE; although its place in clinical practice is not well-defined, it may be recommended in active patients with no response or good tolerance to standard therapies. Hydroxichloroquine improves survival, decreases the risk of thrombosis and flares and is safe in pregnancy, and should be considered the baseline therapy in most SLE patients. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  19. Outcome of deceased donor renal transplantation - A single-center experience from developing country

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    Himanshu V Patel

    2013-01-01

    Full Text Available Renal transplantation (RTx is considered as the best therapeutic modality for patient suffering from end-stage renal disease (ESRD. Dearth of donor kidneys is a major problem everywhere, and deceased donor renal transplantation (DDRTx is seen as at least a partial solution. Even so, DDRTx accounts for only less than 4% of RTx in India. We report our 6-year single-center experience on DDRTx vis-à-vis patient/graft survival, graft function in terms of serum creatinine (SCr, rejection episodes, and delayed graft function (DGF. Between January 2005 and March 2011, 236 DDRTx were performed. Majority of the donors were those with brain death due to road traffic/cerebrovascular accidents. The commonest recipient diseases leading to ESRD were chronic glomerulonephritis (42.8%, diabetes (12.7%, and hypertension (10.6%. Mean recipient age was 36.2 ± 14.2 years; 162 were males and 74 were females. Mean donor age was 45.3 ± 17.13 years; 144 were males and 92 were females. Mean dialysis duration pre-transplantation was 18.5 ± 2.5 months. All recipients received single-dose rabbit-anti-thymocyte globulin induction and steroids, calcinueurin inhibitor, and mycophenolate mofetil/azathioprine for maintenance immunosuppression. Delayed graft function was observed in 29.6% patients and 22% had biopsy-proven acute rejection. Over the mean follow-up of 2.18 ± 1.75 years, patient and graft survival rates were 74.57% and 86.8%, respectively, with mean SCr of 1.42 ± 0.66 mg%. DDRTx achieves acceptable graft function with patient/graft survival, encouraging the use of this approach in view of organ shortage.

  20. Update on the management of chronic eczema: new approaches and emerging treatment options

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    Hobart W Walling

    2010-07-01

    Full Text Available Hobart W Walling1, Brian L Swick21Private Practice of Dermatology, Coralville IA, USA; 2University of Iowa Hospitals and Clinics, Departments of Dermatology and Pathology, Iowa City, IA, USAAbstract: Atopic dermatitis (AD is a common disease with worldwide prevalence, affecting up to 20% of children and 3% of adults. Recent evidence regarding pathogenesis has implicated epidermal barrier defects deriving from filagrin mutations with resulting secondary ­inflammation. In this report, the authors comprehensively review the literature on atopic dermatitis therapy, including topical and systemic options. Most cases of AD will benefit from emollients to enhance the barrier function of skin. Topical corticosteroids are first-line therapy for most cases of AD. Topical calcineurin inhibitors (tacrolimus ointment, pimecrolimus cream are considered second line therapy. Several novel barrier-enhancing prescription creams are also available. Moderate to severe cases inadequately controlled with topical therapy may require phototherapy or systemic therapy. The most commonly employed phototherapy modalites are narrow-band UVB, broadband UVB, and UVA1. Traditional systemic therapies include short-term corticosteroids, cyclosporine (considered to be the gold standard, methotrexate, azathioprine, mycophenolate mofetil, and most recently leflunamide. Biologic therapies include recombinant monoclonal antibodies acting on the immunoglobulin E / interleukin-5 pathway (omalizumab, mepolizumab, acting as tumor necrosis factor-a inhibitors (infliximab, etanercept, adalimumab, and acting as T-cell (alefacept and B-cell (rituxumab inhibitors, as well as interferon γ and intravenous immunoglobulin. Efficacy, safety, and tolerability are reviewed for each medication.Keywords: topical corticosteroids, phototherapy, dermatitis

  1. Retrospective analysis of rituximab therapy and splenectomy in childhood chronic and refractory immune thrombocytopenic purpura.

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    Ay, Yilmaz; Karapinar, Tuba H; Oymak, Yesim; Toret, Ersin; Demirag, Bengu; Ince, Dilek; Ozcan, Esin; Moueminoglou, Nergial; Koker, Sultan A; Vergin, Canan

    2016-06-01

    Immune thrombocytopenic purpura (ITP) results from accelerated platelet destruction mediated by autoantibodies to platelet glycoproteins. Some patients with chronic ITP are refractory to all therapies [steroids, intravenous immunoglobulin (IVIG), anti-D and immunosuppresive drugs] and have chronic low platelet counts and episodic bleeding. We retrospectively evaluated the efficacy and safety of rituximab treatment and splenectomy in paediatric patients diagnosed with chronic and refractory ITP who were unresponsive to steroids, IVIG, cyclosporine and mycophenolate mofetil. Records of patients with chronic and refractory ITP in 459 patients with primary ITP who were followed up in our hospital from January 2005 to December 2014 were reviewed. Fifteen of patients received rituximab and/or applied splenectomy. Fifteen chronic ITP patients (10 boys, five girls) with a mean age of 10 years were enrolled in the study. Two of these patients were suffering from Evans syndrome. The median time since diagnosis of ITP was 10 years. The median follow-up duration after starting Rituximab and splenectomy were 13 and 9.5 months, respectively.None of the seven patients who were treated with rituximab achieved a response. A splenectomy was performed in six of the seven patients who had been treated with rituximab. Complete and partial responses were achieved in 67 and 33% of the patients, respectively. We evaluated the clinical characteristics and responses of chronic ITP patients who did not receive rituximab therapy and underwent a splenectomy. The success rate was 100% in the eight patients with chronic and refractory ITP. Rituximab therapy might not be beneficial for some children with severe chronic ITP who are refractory to standard agents. A splenectomy might be useful and preferable to rituximab.

  2. Downregulation of telomerase maintenance-related ACD expression in patients undergoing immunosuppresive therapy following kidney transplantation.

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    Witkowska, Agnieszka; Strzalka-Mrozik, Barbara; Owczarek, Aleksander; Gola, Joanna; Mazurek, Urszula; Grzeszczak, Wladyslaw; Gumprecht, Janusz

    2015-12-01

    Chronic administration of immunosuppressants has been associated with long-term consequences, including a higher risk of neoplasm development. The processes regulating telomere function exert a major influence on human cancer biology. The present study aimed to assess the effect of immunosuppressive therapy on the expression of genes associated with telomere maintenance and protection in patients following renal transplantation. A total of 51 patients that had undergone kidney transplantation and 54 healthy controls were enrolled in the study. The 51 transplant patients received a three-drug immunosuppressive regimen consisting of cyclosporine A, prednisone and mycophenolate mofetil. In stage 1 of the study, the expression profiles of 123 transcripts, which represented 70 genes, were assessed in peripheral mononuclear blood cells using an oligonucleotide microarray technique in 8 transplant recipients and 4 healthy control subjects. Among the analyzed transcripts, the expression levels of 4 differed significantly between the studied groups; however, only the ACD (adrenocortical dysplasia homolog) gene, encoding the telomere-binding protein POT1-interacting protein 1 (TPP1), was sufficiently specific for telomere homeostasis. The expression of ACD was downregulated in transplant recipients (fold change, 2.11; P=0.006). In stage 2 of the study, reverse transcription-quantitative polymerase chain reaction analysis of ACD , DKC1 and hTERT mRNA was conducted for all transplant patients and control subjects. The results confirmed the downregulation of the ACD gene in patients that had received immunosuppressive therapy (P=0.002). The results of the present study indicate that the downregulation of ACD gene transcription, and thus TPP1 protein expression, may enhance the capacity for cell immortalization, despite normal levels of other key telomere maintenance factors, in patients undergoing immunosuppressive therapy. Furthermore, the results indicate that TPP1 has

  3. Seronegative Neuromyelitis Optica Spectrum Disorder following Exposure to Hepatitis B Vaccination

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    Richard Heekin

    2015-04-01

    Full Text Available Controversy exists regarding a potential link between exposure to recombinant hepatitis B vaccine (HBV and central nervous system demyelinating diseases. Here, we present a case of seronegative neuromyelitis optica spectrum disorder (NMOSD following exposure to HBV. A 28-year-old man developed painful eye movements 11 days after exposure to HBV. Within 24 h, he experienced vision loss, ascending numbness, and ataxia. T-spine MRI showed a cord lesion spanning T6-T9. Brain MRI showed bilateral optic nerve contrast enhancement and a right-sided internal capsule lesion. Cerebrospinal fluid analysis was normal, including negative oligoclonal bands and normal IgG index. AQP4-IgG serology was negative. The patient's visual symptoms improved after treatment with steroids and plasma exchange. He received plasma exchange weekly for 4 weeks with decreased numbness and tingling as well as improved coordination. Treatment with mycophenolate mofetil was started, and the patient remains clinically stable with near resolution of his prior symptoms. Neuromyelitis optica is characterized by optic neuritis and/or longitudinally extensive transverse myelitis. While our patient tested seronegative for AQP4-IgG (which remains negative in 10-50% of NMOSD cases, despite testing with the most sensitive assays available, he did meet NMOSD diagnostic criteria. In a literature review, we found 7 cases of NMOSD onset or relapse associated with exposure to various vaccines, but to our knowledge this represents the first published report of NMOSD onset following exposure to HBV. While causality between vaccination and CNS demyelinating disease remains elusive, it is important to report these cases to help develop safer vaccinations and provoke further inquiry into the pathogenesis of NMOSD.

  4. Selective T-cell Ablation with Bismuth-213 Labeled Anti-TCR Alpha Beta as Nonmyeloablative Conditionaing for Allogeneic Canine Marrow Transplantion

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    Bethge, W. A.; Wilbur, D. Scott; Storb, R.; Hamlin, Donald K.; Santos, E. B.; Brechbiel, M. W.; Fisher, Darrell R.; Sandmaier, B. M.

    2003-06-15

    Two major immunological barriers, the host versus graft (HVG) and the graft versus host (GVH) reaction, must be overcome for successful allogeneic hematopoietic stem cell transplantation. T-cells are involved in these barriers in the major histocompatibility complex-identical settings. We hypothesized that selective ablation of T-cells using radioimmunotherapy, together with postgrafting immunosuppression, would ensure stable allogeneic engraftment. We developed a canine model of nonmyeloablative marrow transplantation in which host immune reactions are impaired by a single dose of 2 Gy total body irradiation (TBI), and where both GVH and residual HVG reactions are controlled by postgrafting immunosuppression with mycophenolate mofetil (MMF) and cyclosporine (CSP). We substituted the alpha-emitter bismuth-213 linked to a monoclonal antibody against TCR(alpha,beta)using the metal-binding chelate CHX-A”-DTPA, for 2 Gy TBI. Biodistribution studies using a gamma-emitting indium-111-labeled anti-TCR mAb showed uptake primarily in blood, marrow, lymph nodes, spleen and liver. In a dosimetry study, 4 dogs were treated with 0.13-0.46 mg/kg TCR mAb labeled with 3.7-5.6 mCi/kg (137-207 MBq/kg) Bi-213. The treatment was administered in 6 injections on days -3 and -2 followed by transplantion of dog leukocyte antigen-identical marrow on day 0 and postgrafting immunosuppression with MMF and CSP. Therapy was well tolerated except for elevations of transaminases, which were transient in all but one dog. No other organ toxicities or signs of graft-versus-host-disease were noted. The dogs had prompt allogeneic hematopoietic engraftment and achieved stable mixed donor-host hematopoietic chimerism with donor contributions ranging from 5-55 % with >30 weeks follow up.

  5. The incidence of post-transplant cancer among kidney transplant recipients is associated with the level of tacrolimus exposure during the first year after transplantation.

    Science.gov (United States)

    Lichtenberg, Shelly; Rahamimov, Ruth; Green, Hefziba; Fox, Benjamin D; Mor, Eytan; Gafter, Uzi; Chagnac, Avry; Rozen-Zvi, Benaya

    2017-07-01

    Immunosuppressive therapy plays a major role in the development of post-transplant cancer. In this nested case-control study of kidney transplant recipients (KTRs), we investigated whether the incidence of post-transplant cancer is associated with the level of tacrolimus exposure over time. We screened the Rabin Medical Center database for adults who received kidney transplants between 2001 and 2014 and developed post-transplant cancer (excluding basal and squamous cell skin cancers). They were matched against KTRs without cancer. All patients received a maintenance immunosuppressive treatment with tacrolimus, mycophenolate mofetil and corticosteroids. The degree of exposure to tacrolimus was estimated as the time-weighted average (tTWA) value of tacrolimus blood levels. The tTWA was calculated as the area under the curve divided by time at 1, 6, and 12 months after transplantation and at time of cancer diagnosis. Thirty-two cases were matched against 64 controls. tTWA values above 11 ng/mL at 6 and 12 months after transplantation were associated with odds ratio (OR) of 3.1 (95% CI 1.1-9) and 11.7 (95% CI = 1.3-106), respectively, for post-transplant cancer; and with OR of 5.2 (95% CI 1.3-20.5) and 14.1 (95% CI = 1.5-134.3), respectively, for cancer diagnosed more than 3 years after transplantation. Exposure to a tacrolimus time-weighted average level above 11 ng/mL at 6 or 12 months after kidney transplantation is associated with an increased risk of developing cancer.

  6. Early conversion to a sirolimus-based, calcineurin-inhibitor-free immunosuppression in the SMART trial: observational results at 24 and 36months after transplantation.

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    Guba, Markus; Pratschke, Johann; Hugo, Christian; Krämer, Bernhard K; Pascher, Andreas; Pressmar, Katharina; Hakenberg, Oliver; Fischereder, Michael; Brockmann, Jens; Andrassy, Joachim; Banas, Bernhard; Jauch, Karl-Walter

    2012-04-01

    Early conversion to a calcineurin-inhibitor (CNI)-free maintenance immunosuppression with sirolimus (SRL), mycophenolate mofetil (MMF) and steroids was associated with an improved 1-year renal function as compared with a cyclosporine (CsA)-based regimen (SMART core-study). This observational follow-up describes 132 patients followed up within the SMART study framework for 36months. At 36months, renal function continued to be superior in SRL-treated patients [ITT-eGFR(@36m) : 60.88 vs. 53.72 (CsA) ml/min/1.73m(2) , P=0.031]. However, significantly more patients discontinued therapy in the SRL group 59.4% vs.42.3% (CsA). Patient [99% (SRL) vs.97% (CsA) and graft 96% (SRL) vs.94% (CsA)] survival at 36months was excellent in both arms. There was no difference in late rejection episodes. Late infections and adverse events were similar in both arms except of a higher rate of hyperlipidemia in SRL and a higher incidence of malignancy in CsA-treated patients. In a multivariate analysis, donor age >60years, S-creatinine at conversion >2mg/dl, CMV naïve(-) recipients and immunosuppression with CsA were predictive of an impaired renal function at 36months. Early conversion to a CNI-free SRL-based immunosuppression is associated with a sustained improvement of renal function up to 36months after transplantation. Patient selection will be key to derive long-term benefit and avoid treatment failure using this mTOR-inhibitor-based immunosuppressive regimen. © 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation.

  7. Our first experiences in applying an original method for removal of ABO-isoagglutinins in ABO-incompatible kidney recipients

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    Ignjatović Ljiljana

    2009-01-01

    Full Text Available Background/Aim. Due to improved methods for removal of ABO isoagglutinins and novel immunosuppressive protocols, short and long term outcome in blood group incompatible is similar to blood group compatible kidney transplantation. The aim of this study was to determine the efficacy of our original method for removal of ABO isoagglutinins from the blood in ABO-incompatible kidney allograft recipients. Method. Between 2006 and 2008 twelve patients were transplanted from ABO incompatible living donors. Titers of ABO isoagglutinins were 4-128 (IgG. Immunosuppressive therapy started 14 days before kidney transplantation with rituximab, followed by a triple therapy (prednisone + tacrolimus + mycophenolate mofetil and the first plasma exchange (PE procedure, in which one plasma volume was substituted with albumin and saline on day 7 before transplantation. For selective extracorporeal immunoadsorption, the removed plasma was mixed with donor blood type filtered red blood cells, centrifuged and the supernatant separated and preserved. In the next PE procedure, the removed plasma was replaced with immunoadsorbed plasma, and so on. Titers of ABO agglutinins, renal allograft function and survival were followed-up. Results. The pre-transplant treatment consisting of 1-5 PE procedures and immunosuppressive therapy resulted in target ABO agglutinins titers below 4. During a 10-24 month follow-up three patients had an early acute rejection, one patient acute rejection and hemolytic anemia, two patients surgical complications and one of them lost his graft. In the post-transplant period, the titers of ABO antibodies remained below 4. All the patients had stable kidney allograft function with mean serum creatinine ±SD of 129 ± 45 μmol/l at the end of the study. Conclusion. Our method for removal of ABO antibodies was effective in a limited series of patients and short-term follow-up.

  8. SEVERE (GRADE III-IV ACUTE GRAFT VERSUS HOST DISEASE AFTER ALLOGENEIC HAEMATOPOIETIC STEM CELL TRANSPLANTATION

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    Irena Preložnik-Zupan

    2002-09-01

    Full Text Available Background. Beside greater susceptibility to infections, acute graft host disease is a consequence of the activation of donor T-cells against host antigens. Most common target organs are skin, liver and intestinal mucosis.Methods. In the 6-year period between January 1995 and December 2000, 49 patients were treated with allogeneic haematopoietic stem cell transplantation (allo-HSCT in Transplant unit, Department of Hematology, Clinical Centre Ljubljana. The standard GVHD prophylaxis regimen consisted of cyclosporine and short-course methotrexate. Severe, grade III-IV aGVHD with skin and/or gastrointestinal and/or liver involvement appeared in 16 (32% of the 49 patients.Results. Among the 16 patients with severe aGVHD, 14 had liver involvement, ten gastrointestinal and eight skin involvement. One patient had skin involvement only, the rest of them had combined involvement of two or three organ systems. Routine first-line treatment for aGVHD, given to all 16 pts with severe forms of the disease, was methylprednisolone (MP 2mg/ kg. Six patients with predominant skin involvement responded to MP. Other ten patients with mainly liver and gastrointestinal involvement needed second or even third line aGVHD treatment. These were anti-thymocyte globulin (ATG and/or monoclonal antibodies (OKT3 and/or mycophenolate mofetil (MMF and/or FK506 (tacrolimus. Seven patients died of advanced aGVHD and treatment related infection.Conclusions. Based on our experiences, we conclude that in critically ill patients with severe aGVHD, neutropenia and high risk for opportunistic infection, each day of ineffective MP therapy may have fatal consequences. Simultaneous institution of a combination of corticosteroids and a second-line drug might prove more appropriate for patients with a severe form of aGVHD.

  9. Effect of long-term calcitonin administration on steroid-induced osteoporosis after cardiac transplantation.

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    Kapetanakis, Emmanouil I; Antonopoulos, Athanassios S; Antoniou, Theofani A; Theodoraki, Kassiani A; Zarkalis, Dimitrios A; Sfirakis, Peter D; Chilidou, Despina A; Alivizatos, Peter A

    2005-05-01

    Early, rapid bone loss and fractures after cardiac transplantation are well-documented complications of steroid administration; therefore, we undertook this study on the effects of long-term calcitonin on steroid-induced osteoporosis. Twenty-three heart transplant recipients on maintenance immunosuppression with cyclosporine, mycophenolate mofetil and prednisone were retrospectively studied. All patients received long-term prophylactic treatment with elemental calcium and vitamin D. Twelve (52.2%) patients also received long-term intranasal salmon calcitonin, whereas 11 (47.8%) received none. Bone mineral density and vertebral fractures were assessed at yearly intervals. Statistical comparisons between each group's bone loss during the first year and in the early (1 to 3 years), intermediate (4 to 6 years) and late (7+ years) post-transplantation periods were done. Lumbar spine bone loss was significant during the early follow-up period in the group not receiving calcitonin (0.744 +/- 0.114 g/cm(2) vs 0.978 +/- 0.094 g/cm(2) [p = 0.002]). The calcitonin group showed bone mineral density (BMD) levels within normal average values throughout the study period. BMD increased in the no-calcitonin group during the intermediate (4 to 6 years) and late (7+ years) follow-up periods, with values approaching normal average and no significant difference between the 2 groups (0.988 +/- 0.184 g/cm(2) vs 0.982 +/- 0.088 g/cm(2) [p = 0.944] and 0.89 +/- 0.09 g/cm(2) vs 1.048 +/- 0.239 g/cm(2) [p = 0.474], respectively). Prophylactic treatment with intranasal salmon calcitonin prevents rapid bone loss associated with high-dose steroids early after cardiac transplantation. Long-term administration does not seem warranted in re-establishing BMD.

  10. Effect of hydroxychloroquine on the survival of patients with systemic lupus erythematosus: data from LUMINA, a multiethnic US cohort (LUMINA L).

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    Alarcón, Graciela S; McGwin, Gerald; Bertoli, Ana M; Fessler, Barri J; Calvo-Alén, Jaime; Bastian, Holly M; Vilá, Luis M; Reveille, John D

    2007-09-01

    In patients with systemic lupus erythematosus (SLE), hydroxychloroquine prevents disease flares and damage accrual and facilitates the response to mycophenolate mofetil in those with renal involvement. A study was undertaken to determine whether hydroxychloroquine also exerts a protective effect on survival. Patients with SLE from the multiethnic LUMINA (LUpus in MInorities: NAture vs nurture) cohort were studied. A case-control study was performed within the context of this cohort in which deceased patients (cases) were matched for disease duration (within 6 months) with alive patients (controls) in a proportion of 3:1. Survival was the outcome of interest. Propensity scores were derived by logistic regression to adjust for confounding by indication as patients with SLE with milder disease manifestations are more likely to be prescribed hydroxychloroquine. A conditional logistic regression model was used to estimate the risk of death and hydroxychloroquine use with and without the propensity score as the adjustment variable. There were 608 patients, of whom 61 had died (cases). Hydroxychloroquine had a protective effect on survival (OR 0.128 (95% CI 0.054 to 0.301 for hydroxychloroquine alone and OR 0.319 (95% CI 0.118 to 0.864) after adding the propensity score). As expected, the propensity score itself was also protective. Hydroxychloroquine, which overall is well tolerated by patients with SLE, has a protective effect on survival which is evident even after taking into consideration the factors associated with treatment decisions. This information is of importance to all clinicians involved in the care of patients with SLE.

  11. A2 to B Blood Type Incompatible Deceased Donor Kidney Transplantation in a Recipient Infected with the Human Immunodeficiency Virus: A Case Report.

    Science.gov (United States)

    Forbes, R C; DeMers, A; Concepcion, B P; Moore, D R; Schaefer, H M; Shaffer, D

    With the introduction of the Kidney Allocation System in the United States in December 2014, transplant centers can list eligible B blood type recipients for A2 organ offers. There have been no prior reports of ABO incompatible A2 to B deceased donor kidney transplantation in human immunodeficiency virus-positive (HIV+) recipients to guide clinicians on enrolling or performing A2 to B transplantations in HIV+ candidates. We are the first to report a case of A2 to B deceased donor kidney transplantation in an HIV+ recipient with good intermediate-term results. We describe an HIV+ 39-year-old African American man with end-stage renal disease who underwent A2 to B blood type incompatible deceased donor kidney transplantation. Prior to transplantation, he had an undetectable HIV viral load. The patient was unsensitized, with his most recent anti-A titer data being 1:2 IgG and 1:32 IgG/IgM. Induction therapy of basiliximab and methylprednisolone was followed by a postoperative regimen of plasma exchange, intravenous immunoglobulin, and rituximab with maintenance on tacrolimus, mycophenolate mofetil, and prednisone. He had delayed graft function without rejection on allograft biopsy. Nadir serum creatinine was 2.0 mg/dL. He continued to have an undetectable viral load on the same antiretroviral therapy adjusted for renal function. To our knowledge, this is the first report of A2 to B deceased donor kidney transplantation in an HIV+ recipient with good intermediate-term results, suggesting that A2 donor kidneys may be considered for transplantation into HIV+ B-blood type wait list candidates. Published by Elsevier Inc.

  12. Efficacy and safety of thymoglobulin induction as an alternative approach for steroid-free maintenance immunosuppression in pediatric renal transplantation.

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    Li, Li; Chaudhuri, Abanti; Chen, Amery; Zhao, Xinmeng; Bezchinsky, Maria; Concepcion, Waldo; Salvatierra, Oscar; Sarwal, Minnie M

    2010-12-27

    Given the recent withdrawal of daclizumab (DAC), the safety and efficacy of thymoglobulin (TMG) was tested as an alternative induction agent for steroid-free (SF) immunosuppression in pediatric kidney transplant recipients. Thirteen pediatric renal transplant recipients meeting defined high-risk criteria at transplantation were offered TMG induction and SF immunosuppression with maintenance mycophenolate mofetil and tacrolimus between October 2008 and January 2010. Patients were closely monitored at baseline, 3, 6, 9, and 12 months posttransplant for protocol biopsy and clinical outcomes. Outcomes were compared with 13 consecutively transplanted low-risk patients receiving an established DAC-based SF protocol (Sarwal et al., WA, American Transplant Congress 2003). There was a significant trend for overall decrease in the absolute lymphocyte counts in TMG group (F=5.86, mixed model group effect P=0.02), predominately at 3 months compared with DAC group (0.7±0.6 vs. 2.1±1.0, P=0.0004); however, lymphocyte count was recovered and was back to reference range by 6 months in TMG. There was trend toward more subclinical cytomegalovirus (15% vs. 0%) and BK viremia (17% vs. 0%) in the TMG group, with no differences in the incidence of subclinical Epstein Barr virus viremia (23% vs. 31%) or clinical viral disease. Mean graft function was excellent, and with a minimum follow-up of 6 months, there were no episodes of acute rejection. TMG seems to be a safe alternative induction strategy in patients for SF immunosuppression in pediatric renal transplantation. Extended follow-up and greater enrollment are necessary to fully explore the impact of TMG dosing on viral replication posttransplantation.

  13. Induction treatment with rabbit antithymocyte globulin versus basiliximab in renal transplant recipients with planned early steroid withdrawal.

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    Martin, Spencer T; Roberts, Keri L; Malek, Sayeed K; Tullius, Stefan G; Vadivel, Nidyanandh; De Serres, Sacha; Grafals, Monica; Elsanjak, Abdelaziz; Filkins, Beth Anne; Chandraker, Anil; Gabardi, Steven

    2011-06-01

    To compare the safety and efficacy of rabbit antithymocyte globulin (r-ATG) with basiliximab in renal transplant recipients for whom an early steroid withdrawal (ESW) regimen was planned. Single-center, retrospective, cohort study. Tertiary care medical center, including inpatient hospital stays and outpatient nephrology clinics. Ninety-nine consecutive adult recipients of living- or deceased-donor renal transplants between January 1, 2004, and December 31, 2007, in whom ESW was planned and who received either r-ATG or basiliximab; patients receiving an extended-criteria kidney donation or a donation after cardiac death were excluded. All patients received mycophenolate mofetil and tacrolimus as maintenance therapy with planned ESW. Induction therapy was either r-ATG 1.5 mg/kg/day for 4 days (68 patients) or basiliximab 20 mg on postoperative days 0 and 4 (31 patients). The primary composite end point of biopsy-proven acute rejection (BPAR), graft loss, and death occurred in 6 patients (9%) and 9 patients (29%) in the r-ATG and basiliximab groups at 1 year after transplantation, respectively (p=0.01), with rates of 7% (5/68 patients) and 26% (8/31 patients) for BPAR (p=0.02), 0% and 3% (1/31 patients) for graft loss (p=0.31), and 2% (1/68 patients) and 0% for patient death (p>0.99). Average time to first BPAR was significantly longer in the r-ATG group (mean ± SD 151.4 ± 82.9 vs 53.6 ± 68.4 days, p<0.01). Kidney function at 12 months was similar between the two groups. Rabbit-ATG was associated with a lower frequency and delayed onset of BPAR compared with basiliximab in renal transplant recipients who received an ESW regimen.

  14. Pharmacoepidemiology of anemia in kidney transplant recipients.

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    Winkelmayer, Wolfgang C; Kewalramani, Reshma; Rutstein, Mark; Gabardi, Steven; Vonvisger, Tania; Chandraker, Anil

    2004-05-01

    ABSTRACT. Anemia has long been known to be a complication of end-stage renal disease (ESRD), and it has been linked to cardiovascular morbidity and mortality. Although kidney transplant recipients (KTR) are prone to experiencing cardiovascular outcomes, little is known about the epidemiology of anemia in this population. With few exceptions, studies to date have not fully evaluated the associations between posttransplant anemia (PTA) and medications commonly used in KTR, particularly immunosuppressant drugs, angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB). The authors aimed to specifically investigate possible associations between these drugs and PTA. Detailed medical information was retrospectively collected on 374 consecutive KTR from our transplant clinic. Univariate/multivariate linear regression models were used to test for associations between hematocrit (HCT) and other covariates, and logistic regression models were used to detect independent predictors of PTA, defined as HCT <33%. The mean time since transplantation was 7.7 yr, and mean creatinine was 2.2 mg/dl. The prevalence of PTA was 28.6%. Ten percent of all patients were on erythropoietin therapy, but only 41.6% of patients whose HCT was <30 received this treatment. From multivariate analyses, the authors found that female gender and lower renal function were associated with lower HCT (both P < 0.001). Patients on ACEI had significantly lower HCT (P = 0.005) compared with patients without such treatment. In addition, a significant curvilinear dose-response relationship was found between ACEI dose and HCT. Among the immunosuppressant drugs, mycophenolate mofetil (P = 0.05) and tacrolimus (P = 0.02) were associated with a lower HCT. The authors conclude that PTA is prevalent and undertreated in KTR. Several medications that are possibly modifiable correlates of PTR deserve further study.

  15. Nephrotic Syndrome and Idiopathic Membranous Nephropathy Associated with Autosomal-Dominant Polycystic Kidney Disease

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    Peces, Ramón; Martínez-Ara, Jorge; Peces, Carlos; Picazo, Mariluz; Cuesta-López, Emilio; Vega, Cristina; Azorín, Sebastián; Selgas, Rafael

    2011-01-01

    We report the case of a 38-year-old male with autosomal-dominant polycystic kidney disease (ADPKD) and concomitant nephrotic syndrome secondary to membranous nephropathy (MN). A 3-month course of prednisone 60 mg daily and losartan 100 mg daily resulted in resistance. Treatment with chlorambucil 0.2 mg/kg daily, low-dose prednisone, plus an angiotensin-converting enzyme inhibitor (ACEI) and an angiotensin II receptor blocker (ARB) for 6 weeks resulted in partial remission of his nephrotic syndrome for a duration of 10 months. After relapse of the nephrotic syndrome, a 13-month course of mycophenolate mofetil (MFM) 2 g daily and low-dose prednisone produced complete remission for 44 months. After a new relapse, a second 24-month course of MFM and low-dose prednisone produced partial to complete remission of proteinuria with preservation of renal function. Thirty-six months after MFM withdrawal, complete remission of nephrotic-range proteinuria was maintained and renal function was preserved. This case supports the idea that renal biopsy is needed for ADPKD patients with nephrotic-range proteinuria in order to exclude coexisting glomerular disease and for appropriate treatment/prevention of renal function deterioration. To the best of our knowledge, this is the first reported case of nephrotic syndrome due to MN in a patient with ADPKD treated with MFM, with remission of proteinuria and preservation of renal function after more than 10 years. Findings in this patient also suggest that MFM might reduce cystic cell proliferation and fibrosis, preventing progressive renal scarring with preservation of renal function. PMID:21552769

  16. Nephrotic Syndrome and Idiopathic Membranous Nephropathy Associated with Autosomal-Dominant Polycystic Kidney Disease

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    Ramón Peces

    2011-01-01

    Full Text Available We report the case of a 38-year-old male with autosomal-dominant polycystic kidney disease (ADPKD and concomitant nephrotic syndrome secondary to membranous nephropathy (MN. A 3-month course of prednisone 60 mg daily and losartan 100 mg daily resulted in resistance. Treatment with chlorambucil 0.2 mg/kg daily, low-dose prednisone, plus an angiotensin-converting enzyme inhibitor (ACEI and an angiotensin II receptor blocker (ARB for 6 weeks resulted in partial remission of his nephrotic syndrome for a duration of 10 months. After relapse of the nephrotic syndrome, a 13-month course of mycophenolate mofetil (MFM 2 g daily and low-dose prednisone produced complete remission for 44 months. After a new relapse, a second 24-month course of MFM and low-dose prednisone produced partial to complete remission of proteinuria with preservation of renal function. Thirty-six months after MFM withdrawal, complete remission of nephrotic-range proteinuria was maintained and renal function was preserved. This case supports the idea that renal biopsy is needed for ADPKD patients with nephrotic-range proteinuria in order to exclude coexisting glomerular disease and for appropriate treatment/prevention of renal function deterioration. To the best of our knowledge, this is the first reported case of nephrotic syndrome due to MN in a patient with ADPKD treated with MFM, with remission of proteinuria and preservation of renal function after more than 10 years. Findings in this patient also suggest that MFM might reduce cystic cell proliferation and fibrosis, preventing progressive renal scarring with preservation of renal function.

  17. Childhood Idiopathic Steroid Resistant Nephrotic Syndrome, Different Drugs and Outcome

    International Nuclear Information System (INIS)

    Shah, S. S. H.; Hafeez, F.

    2016-01-01

    Background: The management of steroid resistant nephrotic syndrome (SRNS) is quite difficult in paediatric patients. Not only the remission is difficult but also these patients are at risk of progression to end stage renal disease (ESRD). The goal of treatment is either to achieve complete remission or even partial remission as it is the most important predictor of disease outcome. Methods: This study was conducted at The Children Hospital, Lahore from February 2014 to May 2015. The SRNS patients of either sex between ages of 1-12 years were included with histology showing mesangioproliferative glomerulonephritis (MesangioPGN), focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD). Patients were given different immunosuppressant drugs and steroid 30 mg/m/sup 2/ alternate day therapy on case to case basis and kept on regular follow up to check for response and adverse effects. Results: Total of 105 patients included, 63 (60 percent) male and 42 (40 percent) female patients. The age ranges from 1.08 to 12 years, mean age of 6.53 years and SD of ±3.17. Tacrolimus was the most common drug used 43 (41 percent) patients followed by cyclosporine in 38 (36.2 percent) patients, while Mycophenolate mofetil (MMF) was prescribed in 21 (20 percent) patients. Complete response was in 96 (91.4 percent) initially while partial response was seen in 8 (7.6 percent) patients. On follow up, 92 (87.6 percent) patients showed complete response and partial response was in 5 (4.7 percent) patients. Cushingoid features and hypertrichosis were the most common adverse effect seen. Conclusion: Steroid resistant nephrotic syndrome can be managed well with various immunosuppressant drugs and steroids but treatment should be individualized according to clinical presentation, disease histology and cost/social factors. (author)

  18. Pediatric liver transplantation in 31 consecutive children

    Institute of Scientific and Technical Information of China (English)

    SHEN Zhong-yang; WANG Zi-fa; ZHU Zhi-jun; ZANG Yun-jin; ZHENG Hong; DENG Yong-lin; PAN Cheng; CHEN Xin-guo

    2008-01-01

    Background Although liver transplantation has become a standard therapy for end-stage liver diseases, the experience of pediatric liver transplantation is limited in China. In this article we report our experience in pediatric liver transplantation, and summarize its characters in their indications, surgical techniques, and postoperative managements. Methods Thirty-one children (≤18 years old) underwent liver transplantation in our centers. The mean age at transplantation was 12.4 years old (ranged from 5 months to 18 years) with 7 children being less than 4 years of age at transplantation. The most common diagnosis of patients who underwent liver transplantation were biliary atresia, Wilson's disease, primary biliary cirrhosis, glycogen storage disease, hepatoblastoma, urea cycle defects, fulminant hepatic failure, etc. The surgical procedures included 12 standard (without venovenous bypass), 6 pigyback, 6 reduced-size, 3 split, 3 living donor liver transplantation, and 1 Domino liver transplantation. The triple-drug (FK506, steroid, and mycophenolate mofetil) immunosuppressive regimen was used in most of patients. Patients were followed up for a mean of 21.8 months. Results Five of the 31 patients died during perioperative time; mortality rate was 16.1%. The reasons of death were infections, primary non-function, heart failure, and hypovolemic shock. Postoperative complications in 10 patients included biliary leakage, acute rejection, abdominal infection, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, and pulmonary infection. Overall patient cumulative survival rate at 1-, 3-, and 5-year was 78.1%, 62.6%, 62.6%, respectively.Conclusions The most common indications of pediatric liver transplantation were congenital end-stage liver diseases. According to patients' age and body weight, standard, piggyback, reduced-size, split, or living donor liver transplantation should be performed. Pediatric liver transplantation especially requires higher

  19. JUVENILE SCLERODERMA-what has changed in the meantime?

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    Adrovic, Amra; Sahin, Sezgin; Barut, Kenan; Kasapcopur, Ozgur

    2018-04-22

    Juvenile scleroderma is a rarely seen chronic connective tissue disorder characterized by stiffening of the skin. The frequency of the disease was reported as one per million. According to organ involvement, the disease is divided into two main forms: systemic and localized scleroderma. Since it is uncommon in children, many aspects of the disease remain discussable. With this review, we aimed to revise recent findings and new developments in this rare condition. Skin manifestations are most prominent feature of the systemic form, followed by musculoskeletal and vascular involvement. Cardiovascular, gastrointestinal and renal disorders are rare in childhood. Combination of disease modifying antirheumatic drugs (methotrexate, mycophenolate-mofetil, cyclosporine) and steroid reprents the first line therapy. Bosentan is used for cases with pulmonary hypertension and for extensive digital ulcerations. Biological treatment emerges as a useful treatment option in most severe form of the disease. Localized scleroderma is characterized with sclerodermatosis of the skin. Internal organ involvement is not expected. Classification of the local scleroderma is made according to the size and localization of the skin changes. There are few different therapeutical options but there is no specific therapy for the localized scleroderma. Many data regarding disease features and treatment options in juvenile scleroderma are based on studies among adults. There is a striking need for multicentric, prospective studies among children with juvenile scleroderma.Emerging biological agents and new treatment options are showing promising results. Anyhow, juvenile scleroderma remains a mystery with many aspects of the disease waiting to be solved. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Glycemic Stability Through Islet-After-Kidney Transplantation Using an Alemtuzumab-Based Induction Regimen and Long-Term Triple-Maintenance Immunosuppression.

    Science.gov (United States)

    Nijhoff, M F; Engelse, M A; Dubbeld, J; Braat, A E; Ringers, J; Roelen, D L; van Erkel, A R; Spijker, H S; Bouwsma, H; van der Boog, P J M; de Fijter, J W; Rabelink, T J; de Koning, E J P

    2016-01-01

    Pancreatic islet transplantation is performed in a select group of patients with type 1 diabetes mellitus. Immunosuppressive regimens play an important role in long-term islet function. We aimed to investigate the efficacy of islet transplantation in patients with type 1 diabetes and a previous kidney transplantation using an alemtuzumab-based induction regimen and triple maintenance immunosuppression. Patients with type 1 diabetes, who had received a kidney transplant previously, were treated with alemtuzumab as induction therapy for their first islet transplantation and basiliximab induction therapy for subsequent islet transplantations. Maintenance immunosuppression consisted of triple immunosuppression (tacrolimus, mycophenolate mofetil, and prednisolone). Thirteen patients (age 50.9 ± 9.2 years, duration of diabetes 35 ± 9 years) received a total of 22 islet transplantations. One- and 2-year insulin independence was 62% and 42%, respectively; graft function was 100% and 92%, respectively. HbA1c dropped from 57.2 ± 13.1 (7.4 ± 1.2%) to 44.5 ± 11.8 mmol/molHb (6.2 ± 0.9%) (p = 0.003) after 2 years. Six of 13 patients suffered from severe hypoglycemia before islet transplantation. After transplantation, severe hypoglycemia was restricted to the only patient who lost graft function. Creatinine clearance was unchanged. Islet-after-kidney transplantation in patients with type 1 diabetes using an alemtuzumab-based induction regimen leads to considerable islet allograft function and improvement in glycemic control. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  1. Engraftment versus immunosuppression: cost-benefit analysis of immunosuppression after intrahepatic murine islet transplantation.

    Science.gov (United States)

    Marzorati, Simona; Melzi, Raffaella; Citro, Antonio; Cantarelli, Elisa; Mercalli, Alessia; Scavini, Marina; Piemonti, Lorenzo

    2014-05-27

    Immunosuppression (IS) in islet transplantation (Tx) is a double-edged sword: it prevents immunoreaction but has the potential to impair islet engraftment. The aim of this study was to identify in murine animal models the IS platform with the best balance between these two opposite effects. To study the impact of IS on islet engraftment diabetic C57BL/6 mice were transplanted with 350 syngeneic islets through the portal vein and treated once-daily with either rapamycin (RAPA; 0.1-0.5-1 mg/kg ip), tacrolimus (FK506; 0.1-0.5-1 mg/kg ip), mycophenolate mofetil (MMF; 60-120-300 mg/kg oral) or vehicle for 14 days. Islet function was evaluated by measuring not-fasting glycemia and by performing an IVGTT on days 15 and 30 post-Tx. RAPA ≥0.5 mg/Kg, FK506 ≥0.5 mg/Kg, and MMF ≥120 mg/kg had detrimental effects on islet engraftment but not on the function of islets already engrafted in the liver. The effect on engraftment was irreversible and persisted even after IS withdrawal. The lower dose of IS that did not affect engraftment was tested for preventing rejection in the full mismatch allogeneic Tx BALB/c to C57BL/6 model. RAPA and/or FK506 were inefficient in preventing rejection, even when anti-IL2R mAb was added to the IS regimen. On the other hand, MMF alone or in association with FK506 significantly prolonged the time to islet rejection. IS showed profound dose-dependent deleterious effects on islet cell engraftment. The MMF/FK506 combination proved the best balance with less toxicity at the time of engraftment and more efficacy in controlling graft rejection.

  2. Predictive patterns of early medication adherence in renal transplantation.

    Science.gov (United States)

    Nevins, Thomas E; Robiner, William N; Thomas, William

    2014-10-27

    Patients' adherence with posttransplant immunosuppression is known to affect renal transplant outcomes. Prospectively, individual medication adherence patterns in 195 kidney transplant recipients were quantified with electronic medication monitors. Monitored drugs were mycophenolate mofetil, sirolimus, or azathioprine. Monitoring began at hospital discharge and continued an average of 15±8 months. Patient follow-up for clinical outcomes averaged 8±3 years. Each month's adherence percentage was calculated as the sum of daily adherence percents, divided by the number of evaluable days. During the first 3 months after transplantation, patients (n=44) with declining medication adherence, defined as dropping by 7% or higher (equal to missing 2 days) between months 1 and 2, later experienced lower mean medication adherence for months 6 to 12, 73% versus 92% respectively (Padherence, they also had more frequent (P=0.034) and earlier (P=0.065) acute rejection episodes. This was additionally associated with more frequent (P=0.017) and earlier (P=0.046) death-censored graft loss.In addition, daily medication adherence, expressed as the percentage of doses taken, decreased as the number of prescribed daily doses increased. During the first 3 months after transplantation, adherence with four doses per day averaged 84%, compared to 91% for patients on twice-daily dosing (P=0.024) and 93.5% for patients on once-daily dosing (P=0.008). Early declining medication nonadherence is associated with adverse clinical outcomes. This pattern is detectable during the first 2 months after transplantation. Early detection of nonadherence provides opportunities to target interventions toward patients at the highest risk for adverse behaviors and events.

  3. Chimerism and tolerance without GVHD or engraftment syndrome in HLA-mismatched combined kidney and hematopoietic stem cell transplantation.

    Science.gov (United States)

    Leventhal, Joseph; Abecassis, Michael; Miller, Joshua; Gallon, Lorenzo; Ravindra, Kadiyala; Tollerud, David J; King, Bradley; Elliott, Mary Jane; Herzig, Geoffrey; Herzig, Roger; Ildstad, Suzanne T

    2012-03-07

    The toxicity of chronic immunosuppressive agents required for organ transplant maintenance has prompted investigators to pursue approaches to induce immune tolerance. We developed an approach using a bioengineered mobilized cellular product enriched for hematopoietic stem cells (HSCs) and tolerogenic graft facilitating cells (FCs) combined with nonmyeloablative conditioning; this approach resulted in engraftment, durable chimerism, and tolerance induction in recipients with highly mismatched related and unrelated donors. Eight recipients of human leukocyte antigen (HLA)-mismatched kidney and FC/HSC transplants underwent conditioning with fludarabine, 200-centigray total body irradiation, and cyclophosphamide followed by posttransplant immunosuppression with tacrolimus and mycophenolate mofetil. Subjects ranged in age from 29 to 56 years. HLA match ranged from five of six loci with related donors to one of six loci with unrelated donors. The absolute neutrophil counts reached a nadir about 1 week after transplant, with recovery by 2 weeks. Multilineage chimerism at 1 month ranged from 6 to 100%. The conditioning was well tolerated, with outpatient management after postoperative day 2. Two subjects exhibited transient chimerism and were maintained on low-dose tacrolimus monotherapy. One subject developed viral sepsis 2 months after transplant and experienced renal artery thrombosis. Five subjects experienced durable chimerism, demonstrated immunocompetence and donor-specific tolerance by in vitro proliferative assays, and were successfully weaned off all immunosuppression 1 year after transplant. None of the recipients produced anti-donor antibody or exhibited engraftment syndrome or graft-versus-host disease. These results suggest that manipulation of a mobilized stem cell graft and nonmyeloablative conditioning represents a safe, practical, and reproducible means of inducing durable chimerism and donor-specific tolerance in solid organ transplant recipients.

  4. Medical management of irradiated patients in a radiation accident in Jining, Shandong province

    International Nuclear Information System (INIS)

    Ai Huisheng; Yu Changlin; Qiao Jianhui; Zhang Shi; Guo Mei; Zhang Xignag; Wang Danhong; Sun Qiyun; Niu Wenkai; Li Guang; Yao Bo; Zhou Zhenshan; Luo Weidong; Liu Sugang; He Yaozhong; Chen Jiankui; Li Xiaobing; Hu Kaixun; Chen Ying; Wu Ke; Yang Guoshan; Liu Ying

    2007-01-01

    Objective: To summarize the experience of diagnosis and treatment from the extremely severe bone marrow form of acute radiation sickness and intestinal form of acute radiation sickness. Methods: A nuclear accident occurred in China on October 21st, 2004. Two individuals were accidentally irradiated by a 60 Co source. The two patients were estimated at more than 20-25 Gy and 9-15 Gy of γ-rays exposures, respectively, and were diagnosed as the intestinal form of acute radiation sickness (patient A) and the extremely severe bone marrow form of acute radiation sickness (patient B), respectively. After urgent preparative regimen based on low- dose fludarabine, antilymphocyte globulin and cyclophosphamide, the two patients received HLA-haploidentical (patient A) or HLA-identical (patient B) peripheral blood stem cell transplantation (PBSCT), respectively. Cyclosporin A combined mycophenolate mofetil regimen was used for the prevention of graft-versus-host disease (GVHD). Bone marrow mesenchymal stem cells from donor were injected to bone marrow of patient A additionally. Results: Both peripheral blood and bone marrow examinations showed hemopoietic recovery after PBSCT. Neither of the two patients showed obvious clinical signs specific to GVHD. Patient A died of septicemia and multi-organ failure on the 33rd day after exposure, while patient B died of multi-organ failure with predominant heart failure on the 75th day after exposure. Conclusions: Chromosome analysis of bone marrow and peripheral blood, and electron spin resonance measurement of tooth enamel play a very important role in diagnosis of the very high dose radiation disease. It is possible and feasible to treat acute radiation sickness using HLA-haploidentical or HLA-identical PBSCT. The death of patients is mainly due to infection and multi-organ failure. (authors)

  5. A comparison of the intrasubject variation in drug exposure between generic and brand-name drugs: a retrospective analysis of replicate design trials.

    Science.gov (United States)

    Yu, Yang; Teerenstra, Steven; Neef, Cees; Burger, David; Maliepaard, Marc

    2016-04-01

    The aim of the present study was to investigate whether differences in total and peak drug exposure upon generic substitution are due to differences between formulations or to intrasubject pharmacokinetic variability of the active substance. The study was designed as a retrospective reanalysis of existing studies. Nine replicate design bioequivalence studies representing six drug classes - i.e. for alendronate, atorvastatin, cyclosporin, ebastine, exemestane, mycophenolate mofetil, and ropinirole - were retrieved from the Dutch Medicines Regulatory Authority. In most studies, the intrasubject variability in total and peak drug exposure was comparable for the brand-name [in the range 0.01-0.24 for area under the concentration-time curve (AUCt ) and 0.02-0.29 for peak plasma concentration (Cmax ) on a log scale] and generic (0.01-0.23 for AUCt and 0.08-0.33 for Cmax ) drugs, and was comparable with the intrasubject variability upon switching between those drugs (0.01-0.23 for AUCt and 0.06-0.33 for Cmax ). The variance related to subject-by-formulation interaction could be considered negligible (-0.069 to 0.047 for AUCt and -0.091 to 0.02 for Cmax ). In the investigated studies, the variation in total and peak exposure seen when a patient is switched from a brand-name to a generic drug is comparable with that seen following repeated administration of the brand-name drug in the patient. Only the intrasubject variability seems to play a crucial and decisive role in the variation in drug exposure seen; no additional formulation-dependent variation in exposure is observed upon switching. Thus, our data support that, for the medicines that were included in the present investigation, from a clinical pharmacological perspective, the benefit-risk balance of a generic drug is comparable with that of the brand-name drug. © 2015 The British Pharmacological Society.

  6. Visual compatibility of defibrotide with selected drugs during simulated Y-site administration.

    Science.gov (United States)

    Correard, Florian; Savry, Amandine; Gauthier-Villano, Laurence; Pisano, Pascale; Pourroy, Bertrand

    2014-08-01

    The visual compatibility of a solution of defibrotide (the only drug recommended for treatment and prophylaxis of hepatic venoocclusive disease) with solutions of various drugs commonly administered in bone marrow transplant procedures was studied. Solutions of 43 drug products in concentrations typically used in clinical practice were evaluated in 1:1 mixtures with defibrotide solution in glass tubes kept at room temperature. The evaluated products included antiinfectious, corticoid, sedative, analgesic, and cardiovascular agents widely used for hematopoietic stem cell transplantation and other marrow transplant procedures; in most cases, test solutions were prepared via dilution in or reconstitution with sterile water, 0.9% sodium chloride injection, or 5% dextrose injection. The mixtures were visually observed immediately after manual mixing and at specified time points (60, 150, and 240 minutes). Visual compatibility was defined as the absence of color change, haze, fibers, particles, gas generation, and precipitate formation. The effect of mixing order on visual compatibility was ascertained. Of the 43 tested drug solutions, 36 were found to be visually compatible with the defibrotide solution over the entire four-hour study period. Solutions of 7 drugs (amikacin, furosemide, midazolam, mycophenolate mofetil, nicardipine, tobramycin, and vancomycin) were visually incompatible with defibrotide solution. In some cases, evidence of incompatibility was observed intermittently or was dependent on mixing order. Defibrotide solution was found to be visually compatible with solutions of 36 i.v. products that are likely to be coadministered with the drug in a bone marrow transplant unit. Seven drug solutions were visually incompatible with defibrotide solution. Copyright © 2014 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  7. Renal function in heart transplant patients after switch to combined mammalian target of rapamycin inhibitor and calcineurin inhibitor therapy

    Directory of Open Access Journals (Sweden)

    Helmschrott M

    2017-06-01

    Full Text Available Matthias Helmschrott,1 Rasmus Rivinius,1 Thomas Bruckner,2 Hugo A Katus,1 Andreas O Doesch1 1Department of Cardiology, Angiology, Pneumology, 2Institute for Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany Background: A calcineurin inhibitor (CNI-based immunosuppression combined with mammalian target of rapamycin inhibitors (mTORs seems to be attractive in patients after heart transplantation (HTX in special clinical situations, for example, in patients with adverse drug effects of prior immunosuppression. Previous studies in patients after HTX detected advantageous effects regarding renal function of a tacrolimus (TAC-based vs cyclosporine-A (CSA-based immunosuppression (in combination with mycophenolate mofetil. However, data regarding renal function after HTX in mTOR/CNI patients remain limited. Aim: Primary end point of the present study was to analyze renal function in HTX patients 1 year after switch to an mTOR/CNI-based immunosuppression. Methods: Data of 80 HTX patients after change to mTOR/CNI-based immunosuppression were retrospectively analyzed. Renal function was assessed by measured serum creatinine and by estimated glomerular filtration rate (eGFR calculated from Modification of Diet in Renal Disease equation. Results: Twenty-nine patients received mTOR/CSA-based treatment and 51 patients received mTOR/TAC-based therapy. At time of switch and at 1-year follow-up, serum creatinine and eGFR did not differ significantly between both study groups (all P=not statistically significant. Analysis of variances with repeated measurements detected a similar change of renal function in both study groups. Conclusion: The present study detected no significant differences between both mTOR/CNI study groups, indicating a steady state of renal function in HTX patients after switch of immunosuppressive regimen. Keywords: heart transplantation, cyclosporine A, tacrolimus, risk factors

  8. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation.

    Science.gov (United States)

    Götestam Skorpen, Carina; Hoeltzenbein, Maria; Tincani, Angela; Fischer-Betz, Rebecca; Elefant, Elisabeth; Chambers, Christina; da Silva, Josè; Nelson-Piercy, Catherine; Cetin, Irene; Costedoat-Chalumeau, Nathalie; Dolhain, Radboud; Förger, Frauke; Khamashta, Munther; Ruiz-Irastorza, Guillermo; Zink, Angela; Vencovsky, Jiri; Cutolo, Maurizio; Caeyers, Nele; Zumbühl, Claudia; Østensen, Monika

    2016-05-01

    A European League Against Rheumatism (EULAR) task force was established to define points to consider on use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Based on a systematic literature review and pregnancy exposure data from several registries, statements on the compatibility of antirheumatic drugs during pregnancy and lactation were developed. The level of agreement among experts in regard to statements and propositions of use in clinical practice was established by Delphi voting. The task force defined 4 overarching principles and 11 points to consider for use of antirheumatic drugs during pregnancy and lactation. Compatibility with pregnancy and lactation was found for antimalarials, sulfasalazine, azathioprine, ciclosporin, tacrolimus, colchicine, intravenous immunoglobulin and glucocorticoids. Methotrexate, mycophenolate mofetil and cyclophosphamide require discontinuation before conception due to proven teratogenicity. Insufficient documentation in regard to fetal safety implies the discontinuation of leflunomide, tofacitinib as well as abatacept, rituximab, belimumab, tocilizumab, ustekinumab and anakinra before a planned pregnancy. Among biologics tumour necrosis factor inhibitors are best studied and appear reasonably safe with first and second trimester use. Restrictions in use apply for the few proven teratogenic drugs and the large proportion of medications for which insufficient safety data for the fetus/child are available. Effective drug treatment of active inflammatory rheumatic disease is possible with reasonable safety for the fetus/child during pregnancy and lactation. The dissemination of the data to health professionals and patients as well as their implementation into clinical practice may help to improve the management of pregnant and lactating patients with rheumatic disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  9. Reduced incidence of new-onset diabetes mellitus after renal transplantation with 3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors (statins).

    Science.gov (United States)

    Prasad, G V Ramesh; Kim, S Joseph; Huang, Michael; Nash, Michelle M; Zaltzman, Jeffrey S; Fenton, Stanley S A; Cattran, Daniel C; Cole, Edward H; Cardella, Carl J

    2004-11-01

    Statins have anti-inflammatory effects, modify endothelial function and improve peripheral insulin resistance. We hypothesized that statins influence the development of new-onset diabetes mellitus in renal transplant recipients. The records of all previously non-diabetic adults who received an allograft in Toronto between January 1, 1999 and December 31, 2001 were reviewed with follow-up through December 31, 2002. All patients receiving cyclosporine or tacrolimus, mycophenolate mofetil and prednisone were included. New-onset diabetes was diagnosed by the Canadian Diabetic Association criteria: fasting plasma glucose > or =7.0 mmol/L or 2-h postprandial glucose > or =11.1 mmol/L on more than two occasions. Statin use prior to diabetes development was recorded along with other variables. Cox proportional hazards models analyzing statin use as a time-dependent covariate were performed. Three hundred fourteen recipients met study criteria, of whom 129 received statins. New-onset diabetes incidence was 16% (n = 49). Statins (p = 0.0004, HR 0.238[0.109-0.524]) and ACE inhibitors/ARB (p = 0.01, HR 0.309[0.127-0.750]) were associated with decreased risk. Prednisone dose (p = 0.0001, HR 1.007[1.003-1.010] per 1 mg/d at 3 months), weight at transplant (p = 0.02, HR 1.022[1.003-1.042] per 1 kg), black ethnicity (p = 0.02, HR 1.230[1.023-1.480]) and age > or =45 years (p = 0.01, HR 2.226[1.162-4.261]) were associated with increased diabetes. Statin use is associated with reduced new-onset diabetes development after renal transplantation.

  10. Diffuse vascular damage in a transplanted kidney: an indication for nuclear magnetic resonance?

    Science.gov (United States)

    Burdese, M; Consiglio, V; Mezza, E; Savio, D; Guarena, C; Rossetti, M; Messina, M; Soragna, G; Suriani, C; Rabbia, C; Segoloni, G P; Piccoli, G B

    2005-06-01

    Vascular lesions are an increasing challenge after renal transplantation due to the wider indications for recipients and acceptance criteria for donors. Diagnostic approach and prognostic interpretation are still matter of controversy. The case reported herein may summarize some of the issues in this regard. A 54-year-old woman, on renal replacement therapy since 1974, and a kidney graft recipient from 1975 to 1999, received a second graft in 2001. The donor age was 65 years (cold ischemia 22 hours; two mismatches). The early posttransplant follow-up was characterized by delayed graft function, hypertension, and diabetes. During the initial hypertension workup, renal graft ultrasound (US) Doppler demonstrated increased vascular resistances, stable over time (resistance index 0.74 to 0.77); renal scintiscan displayed homogeneously parenchymoa and angio-magnetic resonance imaging (MRI), an homogeneous parenchymal vascularization. Initial immunosuppression with tacrolimus and steroids was modulated by adding mycophenolate mofetil to taper tacrolimus (to reduce nephrotoxicity and hypertension). Despite this, kidney function slowly deteriorated; serum creatinine reached 3 to 3.5 mg/dL by the second year. After a severe hypertensive crisis with unchanged scintiscan and US doppler examinations, angio-MRI revealed the almost complete disappearance of parenchymal enhancement beyond the lobar arteries. A renal biopsy confirmed the severe vascular damage. The patient was switched to rapamycine and a low-dose of an angiotension converting enzyme (ACE) inhibitor. She did relatively well (serum creatinine 2.2 to 3 mg/dL) for 6 months, when rapid functional impairment forced her to restart hemodialysis. This case, almost paradigmatic of the problems occurring when the rigid vasculature of long-term dialysis patients is matched with "marginal kidneys," suggests that MRI may be a sensible good to define vascular damage in the grafted kidney.

  11. Synergistic effect of cumulative corticosteroid dose and immunosuppressants on avascular necrosis in patients with systemic lupus erythematosus.

    Science.gov (United States)

    Kwon, H H; Bang, S Y; Won, S; Park, Y; Yi, J H; Joo, Y B; Lee, H S; Bae, S C

    2018-01-01

    Objectives Avascular necrosis (AVN) is one of the most common causes of organ damage in patients with systemic lupus erythematosus (SLE) and often causes serious physical disability. The aims of this study were to investigate clinical risk factors associated with symptomatic AVN and to analyze their synergistic effects in a large SLE cohort in Korea. Methods Patients with SLE were enrolled and followed from 1998 to 2014 in the Hanyang BAE Lupus cohort, and damage was measured annually according to the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). AVN was confirmed by imaging study if patients had symptoms. To determine risk factors for AVN, clinical, laboratory and therapeutic variables were analyzed by logistic regression. Relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S) were calculated to measure interactions between significant variables. Results Among 1219 SLE patients, symptomatic AVN was the most common type of musculoskeletal damage (10.8%, n = 132). SLE patients with AVN showed an earlier onset age, demonstrated AVN more commonly in conjunction with certain other clinical manifestations such as renal and neuropsychiatric disorders, and received significantly higher total cumulative corticosteroid dose and immunosuppressive agents than did patients without AVN. However, in multivariable analysis, only two variables including use of a cumulative corticosteroid dose greater than 20 g (odds ratio (OR) 3.62, p = 0.015) and use of immunosuppressants including cyclophosphamide or mycophenolate mofetil (OR 4.51, p AVN. Patients with cumulative corticosteroid dose > 20 g and immunosuppressant use had a 15.44-fold increased risk for AVN, compared with patients without these risk factors ( p AVN in our Korean lupus cohort. Conclusions An individual risk assessment for AVN development should be made prior to and during treatment for SLE

  12. [Renal transplantation in HIV-infected patients in Spain].

    Science.gov (United States)

    Mazuecos, A; Pascual, J; Gómez, E; Sola, E; Cofán, F; López, F; Puig-Hooper, C E; Baltar, J M; González-Molina, M; Oppenheimer, F; Marcén, R; Rivero, M

    2006-01-01

    HIV infection has experienced dramatic improvement in morbidity and mortality with the highly active antiretroviral therapy (HAART). This prompted a reevaluation of organ-solid transplantation as a treatment option for HIV-infected patients. Some trials in the United States have shown that one- and 2-year graft and patient survival is comparable to HIV-negative transplant population. In Europe the experience is still scarce. The aim of this study is to analyse the outcome and the clinical characteristics of HIV-infected patients who received kidney transplantation in Spain in the HAART era. Ten patients were transplanted in our country since 2001. Only one patient was black. The main cause of end-stage renal disease reported was glomerulonephritis. Six of the recipients were coinfected by hepatitis C virus. Inclusion criteria included undetectable HIV viral load and CD4 counts greater than 200/pL. Immunosuppression consisted of steroids, tacrolimus and mycophenolate mofetil, with antibody induction in 4 cases. The median and mean follow-up was 11 and 16.3+/-15.6 (3-46) months, respectively. One recipient lost his graft because of early renal venous thrombosis. The remaining patients are functioning graft with mean serum creatinina level of 1.5 +/- 0.5 mg/dl. Biopsy-proven acute rejection was diagnosed in 4 recipients and was reversed in all cases with antirejection treatment. The plasma HIV RNA levels have remained controlled and CD4 counts have been stable in excess of 200 cell/microL. None of patients have developed AIDS complications. Recipients receiving protease inhibitor-based HAART regimens required significant dosing modification to maintain appropriate tacrolimus levels. Our results show that renal transplantation can be a safe and effective treatment in select HIV-infected patients. Like other series, the acute rejection rate was higher than in non-HIV recipients. The reasons of this rejection incidence remain unknown.

  13. Clinical Outcomes of Lung Transplantation in Patients with Telomerase Mutations

    Science.gov (United States)

    Tokman, Sofya; Singer, Jonathan P.; Devine, Megan S.; Westall, Glen P.; Aubert, John-David; Tamm, Michael; Snell, Gregory I.; Lee, Joyce S.; Goldberg, Hilary J.; Kukreja, Jasleen; Golden, Jeffrey A.; Leard, Lorriana E.; Garcia, Christine K.; Hays, Steven R.

    2017-01-01

    Background Successful lung transplantation (LT) for patients with pulmonary fibrosis from telomerase mutations is limited by systemic complications of telomerase dysfunction including myelosuppression, cirrhosis, and malignancy. We describe clinical outcomes among 14 LT recipients with telomerase mutations. Methods Subjects underwent LT between February 2005 and April 2014 at 5 LT centers. We abstracted data from medical records, focusing on outcomes reflecting post-LT treatment effects likely to be complicated by telomerase mutations. Results The median age of subjects was 60.5 years (IQR 52.0–62.0), 64.3% were male, and the mean post-LT observation time was 3.2 years (SD ±2.9). Eleven subjects had a mutation in telomerase reverse transcriptase, 2 in telomerase RNA component, and 1 had an uncharacterized mutation. Ten subjects were leukopenic post-LT; leukopenia prompted cessation of mycophenolate mofetil in 5 and treatment with filgrastim in 4. Six subjects had recurrent lower respiratory tract infections (LRTI), 7 had acute cellular rejection (ACR) (A1), and 4 developed chronic lung allograft dysfunction (CLAD). Ten LT recipients developed chronic renal insufficiency and 8 experienced acute, reversible renal failure. Three developed cancer, none had cirrhosis. Thirteen subjects were alive at data censorship. Conclusions The clinical course for LT recipients with telomerase mutations is complicated by renal disease, leukopenia prompting a change in the immunosuppressive regimen, and recurrent LTRI. In contrast, cirrhosis was absent, ACR was mild, and development of CLAD was comparable to other LT populations. While posing challenges, lung transplantation may be feasible for patients with pulmonary fibrosis due to telomerase mutations. PMID:26169663

  14. Desensitization protocol in highly HLA-sensitized and ABO-incompatible high titer kidney transplantation.

    Science.gov (United States)

    Uchida, J; Machida, Y; Iwai, T; Naganuma, T; Kitamoto, K; Iguchi, T; Maeda, S; Kamada, Y; Kuwabara, N; Kim, T; Nakatani, T

    2010-12-01

    A positive crossmatch indicates the presence of donor-specific alloantibodies and is associated with a graft loss rate of >80%; anti-ABO blood group antibodies develop in response to exposure to foreign blood groups, resulting in immediate graft loss. However, a desensitization protocol for highly HLA-sensitized and ABO-incompatible high-titer kidney transplantation has not yet been established. We treated 6 patients with high (≥1:512) anti-A/B antibody titers and 2 highly HLA-sensitized patients. Our immunosuppression protocol was initiated 1 month before surgery and included mycophenolate mofetil (1 g/d) and/or low-dose steroid (methylprednisolone 8 mg/d). Two doses of the anti-CD20 antibody rituximab (150 mg/m(2)) were administered 2 weeks before and on the day of transplantation. We performed antibody removal with 6-12 sessions of plasmapheresis (plasma exchange or double-filtration plasmapheresis) before transplantation. Splenectomy was also performed on the day of transplantation. Postoperative immunosuppression followed the same regimen as ABO-compatible cases, in which calcineurin inhibitors were initiated 3 days before transplantation, combined with 2 doses of basiliximab. Of the 8 patients, 7 subsequently underwent successful living-donor kidney transplantation. Follow-up of our recipients showed that the patient and graft survival rates were 100%. Acute cellular rejection and antibody-mediated rejection episodes occurred in 1 of the 7 recipients. These findings suggest that our immunosuppression regimen consisting of rituximab infusions, splenectomy, plasmapheresis, and pharmacologic immunosuppression may prove to be effective as a desensitization protocol for highly HLA-sensitized and ABO-incompatible high-titer kidney transplantation. Copyright © 2010 Elsevier Inc. All rights reserved.

  15. Infectious complications in living-donor kidney transplant recipients undergoing multi-modal desensitization.

    Science.gov (United States)

    Turza, Kristin C; Shafique, Michael; Lobo, Peter I; Sawyer, Robert G; Keith, Douglas S; Brayman, Kenneth L; Agarwal, Avinash

    2014-06-01

    Pre-existing humoral barriers challenge the transplantation of living donor kidneys (LDK) into highly sensitized ABO- and human leukocyte antigen (HLA)-incompatible recipients. Conditioning these LDK recipients' immune systems is required before they undergo transplantation. We hypothesized that medical desensitization would yield higher post-transplantation rates of infection. We conducted a study in which matched controls consisting of non-desensitized (NDS) LDK recipients were compared with desensitized (DS) receipients. Pre-transplantation desensitization included treatment with rituximab and mycophenolate mofetil followed by intravenous immunoglobulin (IVIg) and plasmapheresis. All participants in the study underwent induction therapy and maintenance immunosuppression. Primary outcomes included infection (opportunistic, local, systemic) within 12 mo after transplantation. Twenty-five patients underwent desensitization and LDK transplantation. Graft survival in the DS and NDS groups of patients was 96% and 98%, respectively. The mean 3- and 12-mo serum creatinine concentrations in the DS and NDS groups were 1.1±0.2 mg/dL and 1.2±0.3 mg/dL and 0.95±0.4 mg/dL and 0.73±0.8 mg/dL (p=0.3 and p=0.01), respectively. Thirty-six percent of the patients in the DS group had one or more infections, vs. 28% of those in the NDS group (p=0.1). No difference was observed in the frequency of opportunistic or systemic infections in the two groups. Local infections were statistically significantly more frequent in the DS group (60% vs. 30%, respectively; p=0.02). Pre-operative desensitization in highly sensitized LDK recipients is followed by a similar incidence of opportunistic and systemic infections as in NDS patients. Local infections were significantly more frequent in the DS than in the NDS patients in the study. With careful monitoring of infectious complications, pre-transplant desensitization permits LDK transplantation into highly sensitized patients.

  16. Ruxolitinib in steroid refractory graft-vs.-host disease: a case report

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    Enrico Maffini

    2016-08-01

    Full Text Available Abstract Background Allogeneic hematopoietic stem cell transplantation (HSCT is potentially curative in a variety of hematological malignancies. Graft-vs.-host disease (GvHD remains a life-threatening complication. Standard treatment is high-dose (HD corticosteroids. Steroid-refractory (SR GvHD is associated with poor prognosis. At present, second-line treatment is ill-defined and includes a number of agents. Novel insights into the pathophysiology of acute GvHD (aGvHD highlight the relevant role of the host inflammatory response governed by several kinase families, including Janus kinases (JAK1/2. Ruxolitinib, a JAK1/2 inhibitor approved for intermediate-2/high-risk myelofibrosis, was recently employed in SR-GvHD with encouraging overall response rates. Clinical experience however remains limited. Case presentation A 51-year-old male with refractory anemia with excess blast type-2 underwent a myeloablative allogeneic HSCT from a 9/10 HLA-matched unrelated donor after conditioning with busulfan and cyclophosphamide. GvHD prophylaxis consisted of cyclosporine, methotrexate, and thymoglobulin. CD34+ cells/kg infused were 8.69 × 106 kg. On day 29, the patient developed overall grade IV aGvHD with biopsy proven stage IV gastrointestinal (GI GvHD refractory to HD corticosteroids. Patient conditions rapidly deteriorated and became critical despite the addition of mycophenolate mofetil and budesonide. On day 33, Ruxolitinib was started, and on day 39 the patient clinical conditions gradually improved. Complete resolution of aGvHD was also confirmed by histology on day 54. Conclusions At 5 months from HSCT, the patient is well and in continuous hematological complete remission without flare of GvHD. Ruxolitinib was discontinued on day 156. Ruxolitinib is feasible and effective in SR-aGvHD though large prospective clinical trials are warranted.

  17. Ureaplasma parvum causes hyperammonemia in a pharmacologically immunocompromised murine model.

    Science.gov (United States)

    Wang, X; Greenwood-Quaintance, K E; Karau, M J; Block, D R; Mandrekar, J N; Cunningham, S A; Mallea, J M; Patel, R

    2017-03-01

    A relationship between hyperammonemia and Ureaplasma infection has been shown in lung transplant recipients. We have demonstrated that Ureaplasma urealyticum causes hyperammonemia in a novel immunocompromised murine model. Herein, we determined whether Ureaplasma parvum can do the same. Male C3H mice were given mycophenolate mofetil, tacrolimus, and prednisone for 7 days, and then challenged with U. parvum intratracheally (IT) and/or intraperitoneally (IP), while continuing immunosuppression over 6 days. Plasma ammonia concentrations were determined and compared using Wilcoxon rank-sum tests. Plasma ammonia concentrations of immunosuppressed mice challenged IT/IP with spent broth (median, 188 μmol/L; range, 102-340 μmol/L) were similar to those of normal (median, 226 μmol/L; range, 154-284 μmol/L, p > 0.05), uninfected immunosuppressed (median, 231 μmol/L; range, 122-340 μmol/L, p > 0.05), and U. parvum IT/IP challenged immunocompetent (median, 226 μmol/L; range, 130-330 μmol/L, p > 0.05) mice. Immunosuppressed mice challenged with U. parvum IT/IP (median 343 μmol/L; range 136-1,000 μmol/L) or IP (median 307 μmol/L; range 132-692 μmol/L) had higher plasma ammonia concentrations than those challenged IT/IP with spent broth (p < 0.001). U. parvum can cause hyperammonemia in pharmacologically immunocompromised mice.

  18. Hypothalamic-pituitary sarcoidosis with vision loss and hypopituitarism: case series and literature review.

    Science.gov (United States)

    Anthony, Jeremy; Esper, Gregory J; Ioachimescu, Adriana

    2016-02-01

    Hypothalamic-pituitary (HP) neurosarcoidosis (NS) accounts for 0.5 % cases of sarcoidosis and 1 % of HP masses. Correlative data on endocrine and neurological outcomes is lacking. Retrospective case series and literature review of presentation, treatment and outcome of HP NS. Our series includes 4 men, ages 34-59, followed for a median of 7.3 years (range 1.5-17). All had optic neuropathy, multiple pituitary hormone abnormalities (PHAs) and other organ involvement by sarcoidosis (lung, sino-nasal, brain/spine and facial nerve). Two patients had central diabetes insipidus and one impaired thirst with polydipsia. After treatment with high-dose glucocorticoids, optic neuropathy improved in one case and stabilized in the others. After treatment, HP lesions improved radiologically, but PHAs persisted in all cases. Review of four published series on HP NS in addition to ours yielded 46 patients, age 37 ± 11.8 years, 65 % male. PHAs consisted of anterior hypopituitarism (LH/FSH 88.8 %, TSH 67.4 %, GH 50.0 %, ACTH 48.8 %), hyperprolactinemia (48.8 %) and diabetes insipidus (65.2 %). PHAs were the first sign of disease in 54.3 % patients. Vision problems occurred in 28.3 % patients, but optic neuropathy was not well documented in previous series. Most patients (93.5 %) received high-dose glucocorticoids followed by taper; 50 % also received other immunomodulators, including methotrexate, mycophenolate mofetil, cyclosporine, azathioprine, infliximab and hydrochloroquine. Only 13 % patients showed improvement in PHAs. All-cause mortality was 8.7 %. HP NS is a serious disease requiring multidisciplinary treatment and lifelong follow-up. Prospective multicentric studies are needed to determine a more standardized approach to HP NS and outline predictors of disease outcome.

  19. T-Helper Subsets Cytokine Production in Kidney Transplant Recipients: Diverting Influences and Impact on Graft Outcome

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    Hassan A

    2000-01-01

    Full Text Available A large body of evidence suggests the existence of functionally polarized human T-helper responses based on their profile of cytokine secretion. Human T-helper cell clones can be divided into two mutually exclusive subsets, T-helper cell 1 (Th1 and T-helper cell 2 (Th2. Substantial work in several animal models has demonstrated that allograft rejection is associated with enhanced Th1 activity and tolerance with enhanced Th2. Some studies have not been consistent with this association. In this study, gamma interferon (INF-y and interleukin 4 (IL-4 levels (as indicators of Th1 and Th2 activity, respectively were assayed in supernatant of cultured peripheral lymphocytes. The levels of these cytokines were compared between a study group of 26 stable kidney transplant recipients immunosuppressed with cyclosporine A, corticosteroids and azathioprine or mycophenolate mofetil, and a control group of 10 healthy blood donors. The mean INF-γ and IL-4 levels in the control group were considered as the cutoff levels for comparison. Our results showed that 25/26 of the study patients (96% had low levels of INF-γ compared to 4/10 of the control subjects (40%, (P< 0.05. However, the IL-4 level was high in 10/26 of the study patients (38% and 3/10 of the control subjects (30%, not a statistically significant difference, (P>0.05. In conclusion: These results suggest that well-established graft tolerance may be mediated via depressed Th1 activity rather than enhanced Th2 activity.

  20. Bioequivalence of a new cyclosporine a formulation to Neoral.

    Science.gov (United States)

    David-Neto, Elias; Kakehashi, Erica; Alves, Cristiane Feres; Pereira, Lilian M; de Castro, Maria Cristina R; de Mattos, Renata Maciel; Sumita, Nairo Massakazu; Romano, Paschoalina; Mendes, Maria Elizabete; Nahas, William Carlos; Ianhez, Luiz Estevam

    2004-02-01

    New cyclosporine A (CsA) formulations must prove their bioequivalence to Neoral, the reference CsA formulation, to allow free prescription for the patients. The aim of this study was to compare the pharmacokinetics (PK) of a new CsA formulation (Zinograf-ME), produced by Strides-Arcolab, to Neoral and to demonstrate their interchangeability in stable renal transplant recipients. Twelve-hour PK studies were obtained from 18 (13 M/5 F) adult patients (mean age 44.7 +/- 12 years). They received their renal allografts from 13 cadaver and 5 living donors. Before enrollment, all patients were receiving a third generic CsA for a mean of 48 months. Nine patients were also under azathioprine and 9 under mycophenolate mofetil; 17 received prednisone. A single oral dose of either Zinograf or Neoral was administered. The first PK study was performed with one formulation, and 1 week later, a second PK was done with the other formulation. During the washout period, patients continued taking the third CsA formulation. The drug substitution was done milligram-for-milligram. The CsA whole-blood level was measured by TDx immunoassay. Mean +/- SD of area under the curve (AUC), maximum concentration (C(max)), and concentration at the second hour (C2) of Zinograf were not statistically different from those with Neoral (4019 +/- 1466 vs 3971 +/- 1325 ng x h/mL, 998 +/- 376 vs 1021 +/- 356 ng/mL, and 707 +/- 254 vs 734 +/- 229 ng/mL, respectively). In the same way, the Zinograf 90% confidence interval for either C(max) (-123, +77 ng/mL) or AUC (-214, +311 ng.mL/h) were within the Neoral bioequivalence interval for the same parameters (+/-204 ng/mL and +/-794 ng x mL/h, respectively). These data demonstrate that the ZinografME CsA formulation is bioequivalent to Neoral.

  1. Vorinostat plus tacrolimus and mycophenolate to prevent graft-versus-host disease after related-donor reduced-intensity conditioning allogeneic haemopoietic stem-cell transplantation: a phase 1/2 trial

    NARCIS (Netherlands)

    Choi, S.W.; Braun, T.; Chang, L.; Ferrara, J.L.; Pawarode, A.; Magenau, J.M.; Hou, G.; Beumer, J.H.; Levine, J.E.; Goldstein, S.; Couriel, D.R.; Stockerl-Goldstein, K.; Krijanovski, O.I.; Kitko, C.; Yanik, G.A.; Lehmann, M.H.; Tawara, I.; Sun, Y; Paczesny, S.; Mapara, M.Y.; Dinarello, C.A.; Dipersio, J.F.; Reddy, P.

    2014-01-01

    BACKGROUND: Acute graft-versus-host disease (GVHD) remains a barrier to more widespread application of allogeneic haemopoietic stem-cell transplantation. Vorinostat is an inhibitor of histone deacetylases and was shown to attenuate GVHD in preclinical models. We aimed to study the safety and

  2. Hemofilia A adquirida Acquired hemophilia A

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    Delfina Almagro Vázquez

    2010-12-01

    , extension of activated partial thromboplastin time (APTT, decrease of Factor VIII activity, and presence of Factor VIII inhibitors. AHA treatment includes the control of hemorrhagic manifestations and the suppression of antibody production. The recombinant factor VIIIa (rVIIIaF concentration and the prothrombin-complex concentrations (PCC are considered like the first-line antihemorrhagic treatment. As alternative therapy in some cases the FCIII concentration, the plasmapheresis and extracorporeal immuno-adsorption may be used. The prednisone alone or associated with cyclophosphamide is the firs-line immunosuppressive treatment. In refractory patients it may be administered as a second-line therapy, the Rituximab (anti-CD20. With the use of Azathioprine, Cyclosporine, Vincristine and the Mycophenolate mofetil variable results have been achieved.

  3. Mecanismos moleculares de acción de algunas drogas inmunosupresoras Molecular mechanisms of action of some immunosuppresive drugs

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    Ana C. Liberman

    2008-12-01

    action of mononuclear cells, being T cells the main targets. Immunosuppressive agents have different molecular targets, and an important drawback in their use is that they also inhibit the normal immune system response. Depending on their mode of action, immunosuppressive drugs can be classified in four different groups: antinflammatory drugs of the corticosteroid family, inhibitors of the calcineurin pathway, cytototoxic or antiproliferative drugs and specific antibodies. In this article, we focus on the molecular action of immunosuppressive drugs such as steroids, cyclosporine, tacrolimus, azathioprine, cyclophosphamide, sirolimus, mycophenolate mofetil, leflunomide and specific antibodies, providing data to characterize and improve the use of these agents.

  4. Determinação de cistatina C como marcador de função renal Cystatin C measurement as renal function marker

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    Letícia Aparecida Lopes Neri

    2010-12-01

    measuring levels of serum cystatin C through Behring nephelometer (BN II and correlate results among transplant patients. The assay comprises the reference range of 0:23 to 7:25 mg/l. The intra-assay and inter- assay imprecision rates were 8.73% and 5.38%, respectively. The analytical recovery of cystatin C after addition of control was between 86.7% and 98% (average 92.3%. The stability of cystatin C to room temperature, refrigerated or frozen was tested. The most significant loss was found in samples stored at room temperature, in which up to 10% of the initial concentration was lost. The coefficient of variation was 14.79% for analytical sensitivity. Throughout the process the results were compared with quality control and good results were achieved. After these tests, we compared the correlations between equations for estimating glomerular filtration rate (Cockroft Gault, Nankivell and MDRD and serum cystatin C or serum creatinine in three groups of kidney transplant patients under different immunosuppressive regimens (n = 197 [azathioprine (n = 36, mycophenolate mofetil (n = 131 or sirolimus (n = 30]. CONCLUSION: The nephelometric cystatin C assay may be perfectly suitable for our routine laboratory. The correlations between serum creatinine and the various equations for estimating glomerular filtration are better than those between cystatin C and equations for estimating glomerular filtration in the three groups irrespective of the immunosuppressive therapy used.

  5. Xenotransplantation of uterine leiomyoma in Wistar rats: a pilot study.

    Science.gov (United States)

    Sousa, Willane Bandeira de; Garcia, João Batista Santos; Nogueira Neto, João; Furtado, Pablo Gustavo Ribeiro; Anjos, Jonhnathan Adriano Araújo dos

    2015-07-01

    To evaluate whether xenografts derived from hysterectomized patients would implant successfully and lead to uterine leiomyoma in Wistar rats. This experimental study examined six female Wistar rats implanted with uterine leiomyoma obtained from patients who underwent hysterectomies at the gynecological surgery service of the HUUFMA. The rats were divided into two groups. Group I consisted of three rats in which the uterine leiomyoma had been implanted in the parietal peritoneum, and group II consisted of three rats in which the uterine leiomyoma was implanted in the subcutaneous tissue. The immunosuppressant mycophenolate mofetil (MMF) was administered orally by gavage (at a dose of 40 mg/kg of body weight) to prevent transplant rejection starting 15 days before the transplant and continuing throughout the entire experiment. After four weeks, necrosis and neovascularization were evaluated histologically in both groups and were classified as either absent or present. Lymphocytic inflammatory infiltration was also examined and classified as mild, moderate or intense (by hematoxylin and eosin staining), and fibrosis was classified as grade I-III (by Masson's trichrome staining). Necrosis was absent from all three rats in group I and was observed in only one rat from group II. Neovascularization was present in two rats from group I and in only one rat from group II. The lymphocytic inflammatory infiltrate was mild in two rats and moderate in one rat from group I, and it was moderate in two rats and intense in one rat from group II. Two rats from group 1 exhibited grade III fibrosis, and one rat presented grade I fibrosis. In group II, two rats presented grade I fibrosis and one rat had grade II fibrosis. When necrosis and neovascularization were evaluated as variables, group I demonstrated greater evidence of successful implantation when compared to group II, indicating that the peritoneal implantation technique produces better results than the subcutaneous approach (p

  6. [Small vessel-childhood primary angiitis of the central nervous system: a case report and literature review].

    Science.gov (United States)

    Deng, J; Fang, F; Wang, X H; Ge, M; He, L J; Zhang, N

    2018-02-02

    small angiitis and immunohistochemistry positive for CD3 and CD20. Twenty-seven patients had detailed therapeutic information; 25 of them received immunosuppressive agents, including cyclophosphamide, mycophenolate mofetil and rituximab. One patient died, 26 patients achieved remission with 54% (22/44) had neurological sequelae. Conclusions: SV-cPACNS had varied clinical manifestations, there was no specificity in laboratory and imaging examination and angiography was often negative. The definite diagnosis relied on brain biopsy, which showed lymphocytic inflammation of small vessels. SV-cPACNS tended to relapse and induce neurologic deterioration. Treatment required long-term use of steroids and immunosuppressive agents. Rituximab could be an effective agent.

  7. Childhood sarcoidosis: A rare but fascinating disorder

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    Gedalia Abraham

    2008-09-01

    of sarcoidosis with questionable efficacy. The high toxicity profile of these agents, including an increased risk of lymphoproliferative disorders and carcinomas, has limited their use to patients with severe disease refractory to other agents. Successful steroid sparing treatment with mycophenolate mofetil was described in an adolescent with renal-limited sarcoidosis complicated by renal failure. Novel treatment strategies for sarcoidosis have been developed including the use of TNF-alpha inhibitors, such as infliximab. The long-term course and prognosis is not well established in childhood sarcoidosis, but it appears to be poorer in early-onset disease.

  8. Low Radiation Dose and Low Cell Dose Increase the Risk of Graft Rejection in a Canine Hematopoietic Stem Cell Transplantation Model.

    Science.gov (United States)

    Lange, Sandra; Steder, Anne; Glass, Änne; Killian, Doreen; Wittmann, Susanne; Machka, Christoph; Werner, Juliane; Schäfer, Stephanie; Roolf, Catrin; Junghanss, Christian

    2016-04-01

    The canine hematopoietic stem cell transplantation (HSCT) model has become accepted in recent decades as a good preclinical model for the development of new transplantation strategies. Information on factors associated with outcome after allogeneic HSCT are a prerequisite for designing new risk-adapted transplantation protocols. Here we report a retrospective analysis aimed at identifying risk factors for allograft rejection in the canine HSCT model. A total of 75 dog leukocyte antigen-identical sibling HSCTs were performed since 2003 on 10 different protocols. Conditioning consisted of total body irradiation at 1.0 Gy (n = 20), 2.0 Gy (n = 40), or 4.5 Gy (n = 15). Bone marrow was infused either intravenously (n = 54) or intraosseously (n = 21). Cyclosporin A alone or different combinations of cyclosporine A, mycophenolate mofetil, and everolimus were used for immunosuppression. A median cell dose of 3.5 (range, 1.0 to 11.8) total nucleated cells (TNCs)/kg was infused. Cox analyses were used to assess the influence of age, weight, radiation dose, donor/recipient sex, type of immunosuppression, and cell dose (TNCs, CD34(+) cells) on allograft rejection. Initial engraftment occurred in all dogs. Forty-two dogs (56%) experienced graft rejection at median of 11 weeks (range, 6 to 56 weeks) after HSCT. Univariate analyses revealed radiation dose, type of immunosuppression, TNC dose, recipient weight, and recipient age as factors influencing long-term engraftment. In multivariate analysis, low radiation dose (P rejection. Peripheral blood mononuclear cell chimerism ≥30% (P = .008) and granulocyte chimerism ≥70% (P = .023) at 4 weeks after HSCT were independent predictors of stable engraftment. In summary, these data indicate that even in low-dose total body irradiation-based regimens, the irradiation dose is important for engraftment. The level of blood chimerism at 4 weeks post-HSCT was predictive of long-term engraftment in the canine HSCT

  9. What is the impact of immunosuppressive treatment on the post-transplant renal osteopathy?

    Science.gov (United States)

    Blaslov, Kristina; Katalinic, Lea; Kes, Petar; Spasovski, Goce; Smalcelj, Ruzica; Basic-Jukic, Nikolina

    2014-05-01

    Although glucocorticoid therapy is considered to be the main pathogenic factor, a consistent body of evidence suggests that other immunosuppressants might also play an important role in the development of the post-transplant renal osteopathy (PRO) through their pleiotropic pharmacological effects. Glucocorticoids seem to induce osteoclasts' activity suppressing the osteoblasts while data regarding other immunosuppressive drugs are still controversial. Mycophenolate mofetil and azathioprine appear to be neutral regarding the bone metabolism. However, the study analyzing any independent effect of antimetabolites on bone turnover has not been conducted yet. Calcineurin inhibitors (CNIs) induce trabecular bone loss in rodent, with contradictory results in renal transplant recipients. Suppression of vitamin D receptor is probably the underlying mechanism of renal calcium wasting in renal transplant recipients receiving CNI. In spite of an increased 1,25(OH)2 vitamin D level, the kidney is not able to reserve calcium, suggesting a role of vitamin D resistance that may be related to bone loss. More efforts should be invested to determine the role of CNI in PRO. In particular, data regarding the role of mammalian target of rapamycin inhibitors (mTORi), such as sirolimus and everolimus, in the PRO development are still controversial. Rapamycin markedly decreases bone longitudinal growth as well as callus formation in experimental models, but also lowers the rate of bone resorption markers and glomerular filtration in clinical studies. Everolimus potently inhibits primary mouse and human osteoclast activity as well as the osteoclast differentiation. It also prevents the ovariectomy-induced loss of cancellous bone by 60 %, an effect predominantly associated with a decreased osteoclast-mediated bone resorption, resulting in a partial preservation of the cancellous bone. At present, there is no clinical study analyzing the effect of everolimus on bone turnover in renal

  10. Combined Haploidentical and Umbilical Cord Blood Allogeneic Stem Cell Transplantation for High-Risk Lymphoma and Chronic Lymphoblastic Leukemia.

    Science.gov (United States)

    Hsu, Jingmei; Artz, Andrew; Mayer, Sebastian A; Guarner, Danielle; Bishop, Michael R; Reich-Slotky, Ronit; Smith, Sonali M; Greenberg, June; Kline, Justin; Ferrante, Rosanna; Phillips, Adrienne A; Gergis, Usama; Liu, Hongtao; Stock, Wendy; Cushing, Melissa; Shore, Tsiporah B; van Besien, Koen

    2018-02-01

    Limited studies have reported on outcomes for lymphoid malignancy patients receiving alternative donor allogeneic stem cell transplants. We have previously described combining CD34-selected haploidentical grafts with umbilical cord blood (haplo-cord) to accelerate neutrophil and platelet engraftment. Here, we examine the outcome of patients with lymphoid malignancies undergoing haplo-cord transplantation at the University of Chicago and Weill Cornell Medical College. We analyzed 42 lymphoma and chronic lymphoblastic leukemia (CLL) patients who underwent haplo-cord allogeneic stem cell transplantation. Patients underwent transplant for Hodgkin lymphoma (n = 9, 21%), CLL (n = 5, 12%) and non-Hodgkin lymphomas (n = 28, 67%), including 13 T cell lymphomas. Twenty-four patients (52%) had 3 or more lines of therapies. Six (14%) and 1 (2%) patients had prior autologous and allogeneic stem cell transplant, respectively. At the time of transplant 12 patients (29%) were in complete remission, 18 had chemotherapy-sensitive disease, and 12 patients had chemotherapy-resistant disease. Seven (17%), 11 (26%), and 24 (57%) patients had low, intermediate, and high disease risk index before transplant. Comorbidity index was evenly distributed among 3 groups, with 13 (31%), 14 (33%), and 15 (36%) patients scoring 0, 1 to 2, and ≥3. Median age for the cohort was 49 years (range, 23 to 71). All patients received fludarabine/melphalan/antithymocyte globulin conditioning regimen and post-transplant graft-versus-host disease (GVHD) prophylaxis with tacrolimus and mycophenolate mofetil. The median time to neutrophil engraftment was 11 days (range, 9 to 60) and to platelet engraftment 19.5 days (range, 11 to 88). Cumulative incidence of nonrelapse mortality was 11.6% at 100 days and 19 % at one year. Cumulative incidence of relapse was 9.3% at 100 days and 19% at one year. With a median follow-up of survivors of 42 months, the 3-year rates of GVHD relapse free survival

  11. Comparison of outcomes in hematological malignancies treated with haploidentical or HLA-identical sibling hematopoietic stem cell transplantation following myeloablative conditioning: A meta-analysis

    Science.gov (United States)

    Guo, Dan; Xu, Peipei; Chen, Bing

    2018-01-01

    Purpose Haploidentical and human leukocyte antigen (HLA)-identical sibling hematopoietic stem transplantation are two main ways used in allogeneic hematopoietic stem cell transplantation (allo-HSCT). In recent years, remarkable progress has been made in haploidentical allo-HSCT (HID-SCT), and some institutions found HID-SCT had similar outcomes as HLA-identical sibling allo-HSCT (ISD-SCT). To clarify if HID-SCT has equal effects to ISD-SCT in hematologic malignancies, we performed this meta-analysis. Methods Relevant articles published prior to February 2017 were searched on PubMed. Two reviewers assessed the quality of the included studies and extracted data independently. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated for statistical analysis. Results Seven studies including 1919 patients were included. The rate of platelet engraftment is significantly lower after HID-SCT versus ISD-SCT while there is no difference in neutrophil engraftment (OR = 2.58, 95% CI = 1.70–3.93, P SCT versus ISD-SCT (OR = 1.88, 95% CI = 1.42–2.49, P SCT group (OR = 0.70, 95% CI = 0.55–0.90, P = 0.005). The incidence rates of overall survival (OS) and disease-free-survival/leukemia-free survival/relapse-free survival (DFS/LFS/RFS) after ISD-SCT are all significantly superior to HID-SCT (OR = 1.32, 95% CI = 1.08–1.62, P = 0.006; OR = 1.25, 95% CI = 1.03–1.52, P = 0.02). There is no significant difference in transplantation related mortality (TRM) rate after HID-SCT and ISD-SCT. Conclusion After myeloablative conditioning, patients receiving ISD-SCT have a faster engraftment, lower acute GVHD and longer life expectancy compared to HID-SCT with GVHD prophylaxis (cyclosporine A, methotrexate, mycophenolate mofetil and antithymoglobulin; CsA + MTX + MMF + ATG). Currently, HID-SCT with GVHD prophylaxis (CsA + MTX + MMF + ATG) may not replace ISD-SCT when HLA-identical sibling donor available. PMID:29381772

  12. Pre-clinical heterotopic intrathoracic heart xenotransplantation: a possibly useful clinical technique.

    Science.gov (United States)

    Abicht, Jan-Michael; Mayr, Tanja; Reichart, Bruno; Buchholz, Stefan; Werner, Fabian; Lutzmann, Isabelle; Schmoeckel, Michael; Bauer, Andreas; Thormann, Michael; Langenmayer, Martin; Herbach, Nadja; Pohla, Heike; Herzog, Rudolf; McGregor, Christopher G A; Ayares, David; Wolf, Eckhard; Klymiuk, Nikolai; Baehr, Andrea; Kind, Alexander; Hagl, Christian; Ganswindt, Ute; Belka, Claus; Guethoff, Sonja; Brenner, Paolo

    2015-01-01

    As a step towards clinical cardiac xenotransplantation, our experimental heterotopic intrathoracic xenotransplantation model offers a beating and ejecting donor heart while retaining the recipient's native organ as a backup in case of graft failure. Clinically applicable immunosuppressive regimens (IS) were investigated first, then treatments known to be effective in hypersensitized patients or those with recalcitrant rejection reactions. Consecutive experiments were carried out between 2009 and 2013. Twenty-one genetically modified pigs (GGTA1-knockout/hCD46/± thrombomodulin, in one case HLA-E instead) were used as donors. In all experiments, two cycles of immunoabsorption reduced preformed antibodies. Recipient baboons were divided into two groups according to IS regimen: In group one (n = 10), pre-treatment started either one (anti-CD20) or four weeks (anti-CD20 plus the proteasome inhibitor bortezomib) prior to transplantation. The extended conventional (as for allotransplantation) immunosuppressive maintenance regimen included anti-thymocyte globuline, tacrolimus, mycophenolate mofetil, methylprednisolone and weekly anti-CD20. In group two (n = 11), myeloablative pre-treatment as in multiple myeloma patients (long and short regimens) was added to extended conventional IS; postoperative total thoracic and abdominal lymphoid irradiation (TLI; single dose of 600 cGY) was used to further reduce antibody-producing cells. In the perioperative course, the surgical technique was safely applied: 19 baboons were weaned off extracorporeal circulation and 17 extubated. Nine animals were lost in the early postoperative course due to causes unrelated to surgical technique or IS regimen. Excluding these early failures, median graft survival times of group 1 and 2 were 18.5 (12-50) days and 16 (7-35) days. Necropsy examination of group 1 donor organs revealed hypertrophy of the left ventricular wall in the six longer-lasting grafts; myocardial histology confirmed pre

  13. Bismuth 213-labeled anti-CD45 radioimmunoconjugate to condition dogs for nonmyeloablative allogeneic marrow grafts

    Energy Technology Data Exchange (ETDEWEB)

    Sandmaier, B M.(Fred Hutchinson Cancer Research Center, Seattle, WA); Bethge, W A.(Fred Hutchinson Cancer Research Center, Seattle, WA); Wilbur, D. Scott (Washington, Univ Of); Hamlin, Donald K.(Washington, Univ Of); Santos, E B.(Fred Hutchinson Cancer Research Center, Seattle, WA); Brechbiel, M W.(National Cancer Institute, National Institutes of Health, Bethesda, MD); Fisher, Darrell R.(BATTELLE (PACIFIC NW LAB)); Storb, R. (Fred Hutchinson Cancer Research Center)

    2002-01-01

    To lower treatment-related mortality and toxicity of conventional marrow transplantation, a nonmyeloablative regimen using 200 cGy total-body irradiation (TBI) and mycophenolate mofetil (MMF) combined with cyclosporine (CSP) for postgrafting immunosuppression was developed. To circumvent possible toxic effects of external- beam gamma irradiation, strategies for targeted radiation therapy were investigated. We tested whether the short-lived (46 minutes) alpha-emitter Bi-213 conjugated to an anti-CD45 monoclonal antibody (mAb) could replace 200 cGy TBI and selectively target hematopoietic tissues in a canine model of nonmyeloablative DLA-identical marrow transplantation. Biodistribution studies using iodine 123-labeled anti-CD45 mAb showed uptake in blood, marrow, lymph nodes, spleen, and liver. In a dose-escalation study, 7 dogs treated with the Bi-213-anti-CD45 conjugate (Bi-213 dose, 0.1-5.9 mCi/kg[3.7-218 MBq/kg]) without marrow grafts had no toxic effects other than a mild, reversible suppression of blood counts. On the basis of these studies, 3 dogs were treated with 0.5 mg/kg Bi-213-labeled anti-CD45 mAb (Bi-213 doses, 3.6, 4.6, and 8.8 mCi/kg[133, 170, and 326 MBq/kg]) given in 6 injections 3 and 2 days before grafting of marrow from DLA-identical littermates. The dogs also received MMF (10 mg/kg subcutaneously twice daily the day of transplantation until day 27 afterward) and CSP (15 mg/kg orally twice daily the day before transplantation until 35 days afterward). Therapy was well tolerated except for transient elevations in levels of transaminases in 3 dogs, followed by, in one dog, ascites. All dogs achieved prompt engraftment and stable mixed hematopoietic chimerism, with donor contributions ranging from 30% to 70% after more than 27 weeks of follow-up. These results form the basis for additional studies in animals and the design of clinical trials using Bi-213 as a nonmyeloablative conditioning regimen with minimal toxicity.

  14. Cytomegalovirus infection after liver transplantation: Current concepts and challenges

    Institute of Scientific and Technical Information of China (English)

    Raymund Rabe Razonable

    2008-01-01

    Cytomegalovirus(CMV)is a common viral pathogen that influences the outcome of liver transplantation.In addition to the direct effects of CMV syndrome and tissue-invasive diseases,CMV is associated with an increased predisposition to acute and chronic allograft rejection,accelerated hepatitis C recurrence,and other opportunistic infections,as well as reduced overall patient and allograft survival.Risk factors for CMV disease are often interrelated,and include CMV D+/R-serostatus,acute rejection,female gender,age,use of high-dose mycophenolate mofetil and prednisone,and the overall state of immunity.In addition to the role of CHV-specific CD4+ and CD8+ T lymphocytes,there are data to suggest that functionality of the innate immune system contributes to CMV disease pathogenesis.In one study,liver transplant recipients with a specific polymorphism in innate immune molecules known as Toll-like receptors were more likely to develop higher Ievels of CMV replication and clinical disease.Because of the direct and indirect adverse effects of CMV disease,its prevention,whether through antiviral prophylaxis or preemptive therapy,is an essential component in improving the outcome of liver transplantation.In the majority of transplant centers,antiviral prophylaxis is the preferred strategy over preemptive therapy for the prevention of CMV disease in CMV-seronegative recipients of liver allografts from CMV-seropositive donors(D+/R-).However,the major drawback of antiviral prophylaxis is the occurrence of delayed-onset primary CMV disease.In several prospective and retrospective studies,the incidence of delayed-onset primary CMV disease ranged from 16% to 47% of CMV D+/R-liver transplant recipients.Current data suggests that delayed-onset CMV disease is associated with increased mortality after liver transplantation.Therefore,optimized strategies for prevention and novel drugs with unique modes of action are needed.Currently,a randomized controlled clinical trial is being

  15. Systemic therapy for vulval Erosive Lichen Planus (the 'hELP' trial): study protocol for a randomised controlled trial.

    Science.gov (United States)

    Simpson, Rosalind C; Murphy, Ruth; Bratton, Daniel J; Sydes, Matthew R; Wilkes, Sally; Nankervis, Helen; Dowey, Shelley; Thomas, Kim S

    2016-01-04

    Erosive lichen planus affecting the vulva (ELPV) is a relatively rare, chronic condition causing painful raw areas in the vulvovaginal region. Symptoms are pain and burning, which impact upon daily living. There is paucity of evidence regarding therapy. A 2012 Cochrane systematic review found no randomised controlled trials (RCTs) in this field. Topically administered corticosteroids are the accepted first-line therapy: however, there is uncertainty as to which second-line treatments to use. Several systemic agents have been clinically noted to show promise for ELPV refractory to topically administered corticosteroids but there is no RCT evidence to support these. The 'hELP' study is a RCT with an internal pilot phase designed to provide high-quality evidence. The objective is to test whether systemic therapy in addition to standard topical therapy is a beneficial second-line treatment for ELPV. Adjunctive systemic therapies used are hydroxychloroquine, methotrexate, mycophenolate mofetil and prednisolone. Topical therapy plus a short course of prednisolone given orally is considered the comparator intervention. The trial is a four-armed, open-label, pragmatic RCT which uses a blinded independent clinical assessor. To provide 80 % power for each comparison, 96 participants are required in total. The pilot phase aims to recruit 40 participants. The primary clinical outcome is the proportion of patients achieving treatment success at 6 months. 'Success' is defined by a composite measure of Patient Global Assessment score of 0 or 1 on a 4-point scale plus improvement from baseline on clinical photographs scored by a clinician blinded to treatment allocation. Secondary clinical outcomes include 6-month assessment of: (1) Reduction in pain/soreness; (2) Global assessment of disease; (3) Response at other affected mucosal sites; (4) Hospital Anxiety and Depression Scale scores; (5) Sexual function; (6) Health-related quality of life using 'Short Form 36' and 'Skindex

  16. Outcome of childhood lupus nephritis in Saudi children

    Directory of Open Access Journals (Sweden)

    Sulaiman Mohammed Al-Mayouf

    2017-01-01

    Full Text Available Our aim in this study is to report the long-term renal outcome of a cohort of Saudi children with systemic lupus erythematosus (SLE. All patients with childhood lupus nephritis (cLN proved by renal biopsy seen between January 2000 and June 2015 were reviewed. The renal outcome was assessed according to serum creatinine level, protein/creatinine ratio at the last follow-up visit, and/or evidence of renal impairment during follow-up period and end-stage renal disease (ESRD. Additional outcome measures include accrual damage measured by pediatric adaptation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (pSDI, and death related to SLE was determined. A total of 84 (72 females cLN patients with follow-up duration of 9.3 years (±5.2 were included in this study. The mean current age was 19.4 years (±5.5 and mean age at onset was 9.2 years (±2.4. The most frequent histopathological class was proliferative glomerulonephritis (64.3% followed by membranous nephritis (27.4%. The mean activity and chronicity indices were 5.9 (±3.9 and 2.9 (±2.2, respectively. Renal microthrombosis was found in 9 (10.7% patients. All patients treated with immunosuppressive medications; cyclophosphamide used in 64 followed by mycophenolate mofetil in 42, then azathioprine in 19 patients, while rituximab used in 24 patients. At the last follow-up visit, the mean serum creatinine was 147 umol/L (±197 and the mean protein/ creatinine ratio was 0.8 (± 1.1 while the mean total pSDI was 1.9 (±1.9 and mean renal SDI was 0.7 (±1.1. Sixteen (19% patients had ESRD and eight of them had class IV nephritis. However, there was no significant difference in ESRD by histological class. The overall survival rates were five years: 94% and 10 years: 87%. Infection was the leading cause of mortality. Our patients had severe cLN and required intensive treatment. Despite the survival rate is comparable to other studies, ESRD is more

  17. Cerebral Vasculitis

    Directory of Open Access Journals (Sweden)

    Fariborz Khorvash

    2017-02-01

    protocol for cerebral vasculitis should include initial MRI to assess the degree of parenchymal damage and to detect vessel wall changes, in particular in large-vessel vasculitis. If the results are ambiguous or medium-sized arteries are affected (beyond the spatial resolution of MRI DSA should follow. Small-vessel vasculitides entirely evade detection by vascular imaging and consequently require brain or leptomeningeal biopsy . Exclusion of differential diagnoses: Important differential diagnoses include RCVS,  intracranial atherosclerosis Moyamoy disease, autoimmune encephalopathies and infectious disorder such as varicella zoster virus (VZV vasculopathies or endocarditis. Therapy: Vasculitis is a serious disease that is potentially fatal or leads to permanent disability and requires rapid institution of immunosuppressive treatment. Possible therapeutic options include glucocorticoids, cyclophosphamide, azathioprine, intravenous immunoglobulins and mycophenolate mofetil.

  18. Can a combined screening/treatment programme prevent premature failure of renal transplants due to chronic rejection in patients with HLA antibodies: study protocol for the multicentre randomised controlled OuTSMART trial

    Science.gov (United States)

    2014-01-01

    Background Renal transplantation is the best treatment for kidney failure, in terms of length and quality of life and cost-effectiveness. However, most transplants fail after 10 to 12 years, consigning patients back onto dialysis. Damage by the immune system accounts for approximately 50% of failing transplants and it is possible to identify patients at risk by screening for the presence of antibodies against human leukocyte antigens. However, it is not clear how best to treat patients with antibodies. This trial will test a combined screening and treatment protocol in renal transplant recipients. Methods/Design Recipients >1 year post-transplantation, aged 18 to 70 with an estimated glomerular filtration rate >30 mL/min will be randomly allocated to blinded or unblinded screening arms, before being screened for the presence of antibodies. In the unblinded arm, test results will be revealed. Those with antibodies will have biomarker-led care, consisting of a change in their anti-rejection drugs to prednisone, tacrolimus and mycophenolate mofetil. In the blinded arm, screening results will be double blinded and all recruits will remain on current therapy (standard care). In both arms, those without antibodies will be retested every 8 months for 3 years. The primary outcome is the 3-year kidney failure rate for the antibody-positive recruits, as measured by initiation of long-term dialysis or re-transplantation, predicted to be approximately 20% in the standard care group but transplant dysfunction, incidence of infection, cancer and diabetes mellitus, an analysis of adherence with medication and a health economic analysis of the combined screening and treatment protocol. Blood samples will be collected and stored every 4 months and will form the basis of separately funded studies to identify new biomarkers associated with the outcomes. Discussion We have evidence that the biomarker-led care regime will be effective at preventing graft dysfunction and expect this to

  19. A pilot study to examine the effect of chronic treatment with immunosuppressive drugs on mucociliary clearance in a vagotomized murine model.

    Directory of Open Access Journals (Sweden)

    Abhiram R Bhashyam

    Full Text Available Previously, we have demonstrated that mucociliary clearance (MCC is diminished within the first months after surgery in lung transplant patients and the explanation for the reduction in MCC is unknown. We hypothesized that chronic treatment with a commonly prescribed regimen of immunosuppressive drugs significantly impairs MCC. We tested this hypothesis in a murine model of lung transplantation.Fifteen C57BL/6 mice underwent vagotomy on the right side to simulate denervation associated with lung transplantation in humans. For 6 days, seven mice (controls were intraperitoneally injected with three 100 µL doses of phosphate buffered saline and eight mice (immunosuppressed were injected with three 100 µL injections of tacrolimus (1 mg/kg, mycophenolate mofetil (30 mg/kg, and prednisone (2 mg/kg once daily. Then, mice inhaled the radioisotope (99mtechnetium and underwent gamma camera imaging of their lungs for 6.5 hrs. Counts in the right lung at 1-1.5 hrs and at 6-6.5 hrs were first background-corrected and then decay-corrected to time 0 counts. Decay-corrected counts were then divided by time 0 counts. Retention at each time point was subtracted from 1.00 and multiplied by 100% to obtain percent removed by mucociliary clearance.Although there was a slowing of MCC at 1-1.5 hrs for the immunosuppressed mice, there was no statistical difference in MCC measured at 1-1.5 hrs for the two groups of mice. At 6-6.5 hrs, MCC was significantly slower in the immunosuppressed mice, compared to controls, with 7.78±5.9% cleared versus 23.01±11.7% cleared, respectively (p = 0.006.These preliminary results suggest that chronic treatment with immunosuppressive medications significantly slows MCC in vagotomized C57BL/6 mice. These findings could shed light on why MCC is reduced in lung transplant patients whose lungs are denervated during surgery and who are chronically treated with immunosuppressive drugs post surgery.

  20. Idiopathic membranous nephropathy in pediatric patients: presentation, response to therapy, and long-term outcome

    Directory of Open Access Journals (Sweden)

    Valderrama Elsa

    2007-08-01

    Full Text Available Abstract Background Idiopathic membranous nephropathy (IMN is one of the most common causes of primary nephrotic syndrome in adults. However, it is a relatively rare entity in the pediatric population and there is a paucity of data about the incidence, prognosis, and optimal treatment of IMN in children and adolescents. We conducted this study to evaluate pediatric patients with IMN in order to clarify the presentation, response to therapy, and clinical outcome. Methods A retrospective chart review was performed on patients identified with biopsy-proven IMN between 1988–2005. Patients with systemic lupus erythematosus or hepatitis-related lesions were excluded. The following data were tabulated: age, gender, ethnicity, presenting clinical and laboratory findings, proteinuria in a first morning urine specimen, estimated glomerular filtration rate (GFRe, histopathology, type and duration of treatment, and clinical status at final evaluation. Results 13 cases of IMN were identified out of 460 renal biopsies performed for evaluation of primary kidney disease during the study interval. Mean age was 9.6 ± 4.6, gender 6 M:7 F, ethnicity 8 W:2 B:3 H. At the initial visit hematuria was present in 9 patients, edema in 5, nephrotic-range proteinuria in 5, and hypertension in 3. Mean urinary protein:creatinine ratio 3.3 ± 2.5 and all patients had a normal GFRe. Classic glomerular findings of IMN were seen in all renal specimens, with concomitant interstitial changes in 2 cases. Treatment included an angiotensin converting enzyme inhibitor or angiotensin receptor blocker in 11 cases. Most patients were also given immunosuppressive medications – prednisone in 10, a calcineurin inhibitor in 5, and mycophenolate mofetil or azathioprine in 3 patients. At the last follow-up, 42 ± 35 months after the diagnostic biopsy, 7 children were hypertensive and the urine protein:creatinine ratio was 2.3 ± 3.1. The mean GFRe was 127 ± 57 mL/min/m2. Three patients

  1. Pseudotumor cerebral associado ao uso de ciclosporina após transplante renal Pseudotumor cerebri associated with cyclosporin use following renal transplantation

    Directory of Open Access Journals (Sweden)

    Kellen Micheline A. H Costa

    2010-03-01

    Full Text Available Pseudotumor cerebral (PC é uma síndrome, caracterizada pela presença de hipertensão intracraniana (HIC e sistema ventricular normal. Pacientes submetidos a transplante renal parecem ser mais suscetíveis a desenvolvê-la, devido à terapia com imunossupressores. Ciclosporina (CsA é uma causa rara de PC, pouco descrita na literatura e que deve ser lembrada no diagnóstico diferencial de HIC e papiledema nesses pacientes. Relatamos um caso de um menino de 10 anos, há três anos com enxerto renal, em uso crônico de micofenolato mofetil (MMF, CsA e baixas doses de prednisona que apresentou quadro de cefaleia, vômitos, diplopia e fotofobia. Fundoscopia revelou edema de papila bilateral. Exame do líquor (LCR e de imagem foram normais. Após exclusão de causas secundárias, foi feito diagnóstico de PC devido ao uso crônico de CsA, que, portanto, foi substituída por Sirolimus. O paciente apresentou melhora clínica progressiva, com resolução do papiledema após três mesesPseudotumor cerebri (PC is a syndrome characterized by the presence of intracranial hypertension (ICH and no alteration in the ventricular system. Renal transplanted patients seem more susceptible to develop it due to immunosuppressive therapy. Cyclosporin (CsA is a rare cause of PC, scarcely reported in the literature, and should be considered in the differential diagnosis of ICH and papilledema in those patients. We report the case of a 10-year-old boy, with a renal allograft for three years, on chronic use of mycophenolate mophetil (MMF, CsA, and low doses of prednisone. The patient presented with headache, vomiting, diplopia, and photophobia. Funduscopy showed bilateral papilledema. Cerebrospinal fluid analysis and imaging tests were normal. After excluding secondary causes, PC was diagnosed based on the chronic use of CsA, which was then replaced by sirolimus. After that, the patient progressively improved, and the papilledema resolved in three months

  2. Budget impact analysis of conversion from cyclosporine to sirolimus as immunosuppressive medication in renal transplantation therapy

    Directory of Open Access Journals (Sweden)

    Foroutan N

    2013-10-01

    Full Text Available Naghmeh Foroutan,1 Hamid R Rasekh,1 Jamshid Salamzadeh,1 Hamid R Jamshidi,1 Mohsen Nafar2 1Department of Pharmacoeconomics and Pharmaceutical Management, School of Pharmacy, Shahid Beheshti University of Medical Sciences, 2Department of Kidney Transplantation, Urinary Nephrology Research Center (UNRC, Shahid Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Objectives: The aim of this study was to determine budget impact of conversion from cyclosporine (CsA to sirolimus (SRL in renal transplant therapy (RTT from the perspective of insurance organizations in Iran. Methods: An Excel-based model was developed to determine cost of RTT, comparing current CsA based therapy to an mTOR inhibitor-based therapy regimen. Total cost included both cost of immunosuppressive agents and relative adverse events. The inputs were derived from database of Ministry of Health and insurance organizations, hospital and pharmacy based registries, and available literature that were varied through a one-way sensitivity analysis. According to the model, there were almost 17,000 patients receiving RTT in Iran, out of which about 2,200 patients underwent the operation within the study year. The model was constructed based on the results of a local RCT, in which test and control groups received CsA, SRL, and steroids over the first 3 months posttransplantation and, from the fourth month on, CsA, mycophenolate mofetil (MMF, and steroids were used in the CsA group and SRL, MMF, and steroids were administered in the SRL group, respectively. Results: The estimated cost of RTT with CsA was US$4,850,000 versus US$4,300,000 receiving SRL. These costs corresponded to the cost saving of almost US$550,000 for the payers. Conclusion: To evaluate the financial consequence of adding mTOR inhibitors to the insurers’ formulary, in the present study, a budget impact analysis was conducted on sirolimus. Fewer cases of costly adverse events along with

  3. Prevalence of premature ovarian failure in systemic lupus erythematosus patients treated with immunosuppressive agents in Thailand.

    Science.gov (United States)

    Akawatcharangura, P; Taechakraichana, N; Osiri, M

    2016-04-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease that affects most women of reproductive age. The prevalence of premature ovarian failure (POF) in SLE patients is higher than that in the general population. However, the data on this condition are limited in Asian countries. To determine the prevalence and associated factors of POF in SLE patients who received immunosuppressive therapy. Women aged 18-40 years who were diagnosed with SLE according to the 1997 revised criteria for the classification of SLE or patients with biopsy-proven lupus nephritis were evaluated. All patients had received at least one of the following immunosuppressive agents: cyclophosphamide (CYC), azathioprine, mycophenolate mofetil, chlorambucil or cyclosporine for more than six months. POF was diagnosed in those who had sustained amenorrhea for more than six consecutive months, with a level of estradiol ≤ 110 pmol/L (30 pg/mL) and follicle stimulating hormone ≥40 IU/L. Ninety two SLE patients were included in this study. Mean age at enrollment was 30 ± 6.9 years and disease duration was 103 ± 67.5 months. The mean Systemic Lupus International Collaborating Clinics/ American College of Rheumatology (SLICC/ACR) damage index was 1.7 ± 1.7. Seventy five patients (82%) had lupus nephritis. Sixty four patients (70%) received CYC. Eleven patients (12%) with POF were observed. For the binary logistic regression model, CYC cumulative dosage of more than 10 g was the only independent risk factor of POF (hazard ratio 17.0, 95% CI 1.96-147.72, p = 0.01). From our data, 12% of SLE patients developed POF. A cumulative dose of CYC of more than 10 g was the only risk factor for POF. To prevent these events, systematic evaluation and early recognition of POF should be promoted in the care of SLE patients. © The Author(s) 2015.

  4. Malaria chemoprophylaxis in travellers to east Africa: a comparative prospective study of chloroquine plus proguanil with chloroquine plus sulfadoxine-pyrimethamine

    OpenAIRE

    Fogh, S; Schapira, A; Bygbjerg, I C; Jepsen, S; Mordhorst, C H; Kuijlen, K; Ravn, P; Rønn, A; Gøtzsche, P C

    1988-01-01

    As malaria caused by Plasmodium falciparum has become resistant to chloroquine alternative drug regimens need to be developed. The prophylactic efficacy against malaria and the side effects of chloroquine phosphate 500 mg weekly with proguanil hydrochloride 200 mg daily was compared with the efficacy of chloroquine 500 mg weekly with sulfadoxine 500 mg-pyrimethamine 25 mg weekly in a randomised study of Scandinavian travellers to Kenya and Tanzania during 1984-5. A total of 767 subjects (416 ...

  5. Changes in some biochemical parameters of kidney functions of ...

    African Journals Online (AJOL)

    Yomi

    2012-04-03

    Apr 3, 2012 ... Following one week of intramuscular administration of. 12.5 to 50.0 mg/kg ... of drug administration in those rats that received 50.0 mg/kg of the drug, ... Preparation of thin and thick films and staining technique. A small drop of ...

  6. 76 FR 51417 - Surinder Dang, M.D.; Revocation of Registration

    Science.gov (United States)

    2011-08-18

    ... and handed him a business card listing her name as R.K. and her position as ``president.'' Id. R.K... the latter's report.\\7\\ Id. at 6. \\7\\ More specifically, there were 14 bottles of 500 count of hydrocodone/apap 7.5/500 mg, 10 bottles of 500 count hydrocodone/ apap 10/500 mg, 36 bottles of 500 count...

  7. Persistent Psychosis Occurring in a Patient Receiving Cycloserine ...

    African Journals Online (AJOL)

    A case of cycloserineinduced psychosis persisting after discontinuation of the drug in the treatment of multidrug resistant tuberculosis in a 26 year old male who was been managed in the hospital for multidrug resistant tuberculosis on daily doses of Cycloserine 500mg, Pyrazinamide 1.2g, Proteonamide 500mg, Kanamy c ...

  8. CHAPTER 1

    African Journals Online (AJOL)

    Dr Olaleye

    TNF-α activity in STZ-induced diabetic rats. Wistar rats were randomly divided into groups (n=6) receiving different oral treatments consisting of vehicle, aqueous ginger extract (250 and 500 mg/kg), ethanol ginger extract (250 and 500 mg). The effect of Z. officinale was assessed in the STZ-induced diabetic rats after 6-week ...

  9. Nefropatía por Inmunoglobulina A: Guía de práctica clínica Immunoglobulin A nephropathy: Clinical Practice Guidelines

    Directory of Open Access Journals (Sweden)

    Alicia Fayad

    2011-05-01

    tonsilectomía.Immunoglobulin A nephropathy (N.IgA is the world most common glomerular disease; 15-50% of patients develop loss of renal function in 10-20 years, and the rest remission or mild proteinuria/ hematuria. The optimal treatment is uncertain. Our aim was to develop evidence-based recommendations through research in Medline, Embasse, Lilacs and Cochrane Central Register of Controlled Trials. The study-quality was independently assessed by the reviewers following the Cochrane Renal Group checklist: randomization, blinding, intention-to-treat analysis and follow-up period. Levels of evidence and grades of recommendation were assigned according to Center for Evidence-Based Medicine, Oxford. Two approaches were considered: Immunosuppressive therapy (corticosteroids, cytostatics, cyclosporine A, mycophenolate-mofetil: Level I a, grade A. -Combined suppressive therapy in adults. Corticosteroids plus cytotoxics drugs (cyclophosphamide/azathioprine: Level II b, grade B. In children with severe IgA nephropathy: Level II b, grade D. Cyclosporine and mycophenolate- mophetil: Level II b, grade C. Cyclosporine and mycophenolate-mophetil: Level ll b, grade C. -Non immunosuppressive therapy: reninangiotensin converting enzyme inhibitors (ACEI and/or angiotensin II receptor blockers (ARB, fish oil, statins, antiplatelets and tonsillectomy. ACEI and/or ARB, in patients with proteinuria =1 g: Level I a, grade A. In children with moderate proteinuria: ACEI and/or ARB with close monitoring of renal function and serum potassium level: Level II b, grade B. Antiplatelet as supportive treatment: Level I a, grade C. Fish oil in addition to ACEI or ARB in patients with mild histological lesions: Level II b, grade B (Not in children. Statins: no evidence to recommend these drugs in children. In patients > 5 years with nephrotic syndrome and hyper-cholesterolemia, use statins with close monitoring of serum creatine-kinase. There is no evidence to recommend tonsillectomy.

  10. Evaluación del efecto tóxico de extractos de Eupatorium microphyllum L.F. (Asteraceae) sobre larvas de Aedes aegypti (Diptera: Culicidae) en condiciones de laboratorio

    OpenAIRE

    Bello, Felio J.; Rozo, Álvaro; Zapata, Cristina

    2010-01-01

    En el presente trabajo se evaluó la actividad tóxica de extractos de Eupatorium microphyllum L.F. sobre larvas de IV estadio del mosquito Aedes aegypti (Linneaus), bajo condiciones de laboratorio. Se utilizaron extractos acuosos en concentraciones del 500 mg L-1, 1.500 mg L-1 y 2.500 mg L-1 y acetónicos en concentraciones de 10 mg L-1, 20 mg L-1, 30 mg L-1, 40 mg L-1 y 50 mg L-1. Los bioensayos se realizaron por triplicado, cada uno con 20 larvas, expuestas durante 24 horas a 150 mL de soluci...

  11. Expanded criteria donor kidneys for younger recipients: acceptable outcomes.

    Science.gov (United States)

    Goplani, K R; Kute, V B; Vanikar, A V; Shah, P R; Gumber, M R; Patel, H V; Modi, P R; Trivedi, H L

    2010-12-01

    European senior programme (ESP) is well known for acceptable outcomes using expanded criteria donor (ECD) kidneys from donors older than 65 years for recipients older than 65 years. The incidence of end-stage renal disease (ESRD) is 229/million in India with a mean age of 45 years. We performed a retrospective analysis of transplantation of ECD versus standard criteria donor (SCD) kidneys into younger recipients. Forty-three ECD transplantations among 158 deceased donor organ transplantation (DDOT) were performed between January 2006 and December 2009. Among 43 transplantation from 30 donors, 14 were dual kidney transplantations (DKT) performed based upon biopsy evaluation. All recipients received thymoglobulin (rATG) induction followed by immunosuppression with a steroid, mycophenolate mofetil (MMF), and a calcineurin inhibitor. Statistical analysis used chi-square test and unpaired Student t test. Kaplan-Meier curves were used for survival analysis. For ECD the mean donor age was 64 ± 11 years. Cerebrovascular accidents (CVA) were the cause of death among 60% of donors, 73.13% of whom were hypertensive and 23.13% diabetic. Mean DKT donor age was 75 ± 9.17 years versus 60 ± 8.0 years for single kidney transplantation (SKT). Mean recipient age of DKT versus SKT was 44 ± 12.4 years versus 43 ± 14 years. Mean serum creatinine (SCr; mg/dL) of SKT patients was 1.64 ± 0.75 versus 1.68 ± 0.46 in DKT. Mean follow-up was 455 ± 352 days. Mean SCr of 43 ECD recipients of mean age, 43.4 ± 14.2 years was 1.61 ± 0.61 mg/dL. Among 43 recipients, 23.25% were diabetic, 41.86% displayed delayed graft function (DGF), and 23.25% experienced biopsy-proven acute rejection (BPAR). Patient survival rate was 72.09% and graft survival rate was 67.44%. For SCD transplantations (n = 115), the mean donor age was 36 ± 14 years and recipient mean age was 32.8 ± 14.07 years. Mean SCr was 1.32 ± 0.46 mg/dL with 26.95% recipients displaying DGF, whereas 20.86% had BPAR. In the SCD

  12. [Evaluation of immunosuppressive treatment on homocystein levels in patients after kidney transplantation during a 2 year observation period].

    Science.gov (United States)

    Aksamit, Dariusz; Janda, Katarzyna; Kuźniewski, Marek; Krzanowski, Marcin; Ignacak, Ewa; Betkowska-Prokop, Alina; Chowaniec, Eve; Sułowicz, Wladysław

    2012-01-01

    The aim of the study was to evaluate the influence of the type of prescribed immunosuppression: cyclosporine A (CsA) vs. tacrolimus (Tac) on remote homocystein levels in patients (pts) after kidney transplantation (Ktx). The study included 51 pts (17 F, 34 M) aged 15 to 62 years (mean 38.1) after cadaver Ktx. The mean observation period equaled 21.2 months (6 -24); while total observation period was 90 personlyears. Before Ktx, 46 pts were treated with maintenance hemodialysis (HD), while 5 by peritoneal dialysis (PD). After Ktx, patients had immunosuppression prescribed according to the following schemes: prednisone (P) + CsA + azathioprine (AZA) - 12 pts; P + CsA + mycophenolate mofetil (MMF) -26 pts; P + Tac + MMF - 11 pts; and P + Tac + AZA - 2 pts. Hcy level was measured using high performance liquid chromatography (HPLC). Serum creatinine level was measured by standard method using the Hitachi 917 analyzer. Creatinine clearance was calculated based on the Cockcroft-Gault formula. Patient's blood was drawn before Ktx and 3, 6, 9, 12,15, 18, 21 and 24 months post procedure. Delayed graft function (DGF) after Ktx was diagnosed in 29 pts (56.9%) and this group required from 4 to 28 HD sessions (mean 14 sessions). Hcy level did not significantly differ between pts requiring (29 pts) and not requiring (22 pts) HD treatment after Ktx. It was also noted that the number of performed HD sessions did not significantly correlate with Hcy levels 24 months after Ktx (R =0.04, p=0.81). No relationship was found (non-parametric Spearman test) between the drop in Hcy level 3 months after Ktx as compare with value before Ktx and ischemia time (R=0.09, p=0.49), number of compatible HLA A and B (R=0.07, p=0.63), and DR antigens (R=0.09, p=0.51). Decrease in Hcy level (before Ktx and 24 months after Ktx) did not significantly correlate with the above parameters, respectively: R=-0.14, p=0.40; R=0.06, p=0.73; R=0.12, p=0.45; R=0.11, p=0.50. Decrease in Hcy level (before Ktx and 3

  13. Management of Membranous Nephropathy in Western Countries.

    Science.gov (United States)

    Alfaadhel, Talal; Cattran, Daniel

    2015-09-01

    20.0-36.8% of adult-onset NS cases. The presence of anti-PLA2R antibodies in serum or PLA2R on renal biopsy is the most predictive feature for the diagnosis of IMN and is used in both the East and West; however, appropriate screening to rule out secondary causes should still be performed. (2) Several observational (nonrandomized) Asian studies indicate a good response to corticosteroids alone in IMN patients, although no randomized controlled trials (RCTs) have been done in Asian membranous patients at high risk of progression. Corticosteroid monotherapy has failed in randomized controlled studies in Western countries and is therefore not recommended. (3) Cyclophosphamide is the most commonly prescribed alkylating agent in Europe and China. Also, chlorambucil is still used in some Western countries, particularly in Europe. In North America, CNIs are the more common first-line treatment. (4) Cyclosporine is predominantly used as monotherapy in North America, although KDIGO and Japanese guidelines still recommend a combination with low-dose corticosteroids. Clinical studies both in Asia and Europe showed no or little effects of monotherapy with mycophenolate mofetil compared to standard therapies. (5) There are encouraging data from nonrandomized Western studies for the use of rituximab and a few small studies using adrenocorticotropic hormone. Clinical trials are ongoing in North America to confirm these observations. These drugs are rarely used in Asia. (6) A Chinese study reported that 36% of IMN patients suffered from venous thromboembolism versus 7.3% in a North American study. Prophylactic anticoagulation therapy is usually added to IMN patients with a low risk of bleeding in both Eastern and Western countries. (7) The Chinese traditional medicine herb triptolide, which might have podocyte-protective properties, is used in China to treat IMN. An open-label, multicenter RCT showed that Shenqi, a mixture of 13 herbs, was superior to corticosteroids plus

  14. [Glomerulonephritis and vasculitis as causes of arterial hypertension].

    Science.gov (United States)

    Eicken, Sibylle; Gugger, Mathias; Marti, Hans-Peter

    2012-05-01

    , such as a screening for infections, including search for HIV, hepatitis B or C and various bacteria, and for systemic inflammatory diseases, including tests for antibodies, such as ANA, anti-dsDNA, ANCA, anti-GBM and anti-CCP. In cases of membranous nephropathy, antibodies against phospholipase-A2-receptor need to be looked for. Depending upon the given clinical circumstances and the type of disease, a reasonable tumor screening must be performed, especially in cases of membranous and minimal-change nephropathy. Finally, radiological examinations will complete the initial work-up. In most cases, at least an ultrasound of the kidney is mandatory. Thereafter, in most cases a renal biopsy is required to establish a firm diagnosis to define all treatment options and their chance of success. The elimination of a specific cause for a given glomerulonephritis or vasculitis, such as an infection, a malignancy or a drug-related side-effect, remains the key principle in the management of these diseases. ACE-inhibitors, angiotensin receptor-blockers, aldosteron antagonists and renin-inhibitors remain the mainstay in the therapy of arterial hypertension with proteinuria. Only in cases of persistently high proteinuria, ACE-inhibitors and angiotensin receptor blockers can be prescribed in combination. Certain types of glomerulonephritis and essentially all forms of vasculitis require some form of more specific anti-inflammatory therapy. Respective immunosuppressive drug regimens contain traditionally medications, such as glucocorticoids (e. g. prednisone), cyclosporine A, mycophenolate mofetil, cyclophosphamide, and azathioprine. With respect to more severe forms of glomerulonephritis and vasculitis, the antibody rituximab represents a new and less toxic alternative to cyclophosphamide. Finally, in certain special cases, like Goodpasture's syndrome or severe ANCA-positive vasculitis, a plasma exchange will be useful and even required.

  15. Cytomegalovirus disease in renal transplant recipients: a single-center experience.

    Science.gov (United States)

    Bhadauria, Dharmendra; Sharma, R K; Kaul, A; Prasad, Narayan; Gupta, Amit; Gupta, Anurag; Srivastava, Aneesh

    2012-09-01

    Cytomegalovirus (CMV) is the most common viral infection following kidney transplant, has been recognized as a major factor for graft loss and increased incidence of acute rejection. Different studies have reported a variable incidence of CMV disease with the use of Mycophenolate mofetil (MMF). We retrospectively analyzed our renal transplant recipients to review the results of CMV disease and to compare CMV disease in patient on Azathioprine and MMF for this purpose we retrospectively reviewed 521 live related kidney transplant recipients at our institute. 74 (14.2 %) live related allograft recipients developed CMV disease after a median interval of 7.18 ± 4.35 months from transplantation. The mean age was 36.15 ± 10.7 years. 63 of the patients were male. Malaise, fever and diarrhea were among most common symptoms. 20 (27.02 %) of the 74 recipients developed transaminitis, 13 (17.2 %) developed CMV gastritis, 5 (9.13 %) recipients developed pneumonia, and 3 (4.05 %) patient developed colitis. 59 (80 %) patients had leucopenia and 41 (56.5 %) developed thrombocytopenia. Mean serum creatinine level was 1.5 ± 0.4 (0.9-2.4) mg/dl before the disease, 1.9 ± 0.6 (1.3-3.6) mg/dl at the time of the diagnosis, and 1.7 ± 0.06 (0.8-4.2) mg/dl at the end of the treatment. CMV disease developed in 9 (36 %) of recipients who received basiliximab as induction therapy and 13 (30.24 %) of recipients who received ATG (p > 0.05). The incidence of CMV disease was similar in cyclosporine based regimen (13.2 %) and Tacrolimus based regimen 27 (16.16 %) (p = 0.137) and was also similar in Azathioprine 41 (9.5 %) and MMF group 33 (14.3 %) (p = 0.163). There was no significant difference in severity of CMV disease in both groups, except a higher incidence of leucopenia in Azathioprine group (86 vs. 74 %, p < 0.05) as compared to MMF group. 51 (68.91 %) patient developed graft dysfunction during CMV disease. In conclusion we report a low incidence

  16. 46例老年肾移植患者疗效评价%Evaluation of renal transplantation in 46 geriatric patients

    Institute of Scientific and Technical Information of China (English)

    魏秀举; 马韬

    2014-01-01

    Objective To summarize the experience of clinical treatment in elderly patients after renal transplantation,and to evaluate its curative effect. Methods Forty-six cases of renal transplantation patients over the age of 60 admitted to the Third People's Hospital of Shanxi Datong from September 1998 to June 2010 were retrospectively analyzed. From 1998 to 2005,patients were treated with triple drug use(20 cases),prednisone(Pre), cyclosporineA(CsA)and mycophenolate mofetil(MMF). From 2005 to 2010,patients were treated with triple drug use(26 cases),methylprednisolone(MP),tacrolimus(FK506)and MMF. Results In these 46 cases of geriatric renal transplant patients,postoperative complications were happened in 12 cases(26.1%),pulmonary infection in 4 cases,urinary tract infection in 4 cases,upper respiratory tract infection in 3 cases,herpes virus infection in 1 case, acute rejection(AR)in 9 cases(19.6%),and 3 cases(6.5%)died of heart failure. Transplantation kidney and the patients were alive in the other 43 cases. During the follow-up,3 cases got chronic allograft nephropathy,2 of whom had experienced AR. Conclusions The patients over 60 years old can receive kidney transplantation successfully. The main reasons leading to death were cardiac complication and infection. The indication of recipients and using of immunosuppressive agent properly are the keys to prolong the survival time.%目的:总结老年肾移植患者的临床治疗经验,并对其疗效进行评价。方法回顾性分析山西省大同市第三人民医院1998年9月至2010年6月间60岁以上的肾移植患者46例,1998年至2005年,患者采用泼尼松(Pre)、环孢素A(CsA)及吗替麦考酚酯(MMF)三联免疫抑制剂治疗(20例);2005年至2010年,患者采用甲泼尼龙(MP),他克莫司(FK506)及MMF三联免疫抑制剂治疗(26例)。结果46例老年肾移植患者中,术后发生并发症12例(26.1%),4例肺部感染,4例尿

  17. Simultaneous hepatorenal transplantation:two cases report%肝肾联合移植二例报告

    Institute of Scientific and Technical Information of China (English)

    郑树森; 梁廷波; 陈江华; 黄东胜; 张珉; 王逸民

    2000-01-01

    Objectives To investigate the surgical techniques,clinical experiences and therapeutic effects of simultaneous hepatorenal transplantation.Methods Simultaneous hepatorenal transplantation was performed on one patient with liver cirrhosis of hepatitis B and uremia of chronic nephritis and one with liver cirrhosis of hepatitis B complicated with hepatorenal syndrome.Infosion in situ of the donors' organs was carried out by UW solution and multiple organs were harvested.Liver and kidney transplantation was carried out by using orthotopic and ordinary methods respectively.Ilmnunosuppressive drugs consisted of cyclosporine,mycophenolate mofetil,ALG and corticosteroid.Lamividine was used on day 50 and day 40postoperation respectively.Results Both transplant organs had rapidly normal functions postoperation,and the patient recovered well but suffered from mild kidney rejection on the 110 postoperative day in case 1.In case 2,acute renal function failure,mental symptoms,muscle spasm,cerebral artery thrombosis,inhale pneumonia and chronic liver graft rejection ensued sequentially but passed at over the end.The patients have been survived for 4 and 3 months respectively with normallire quality.Conclusions Combined hepatorenal transplant is one of the treatment methods for liver and kidney function failure but requiring more comprehensive techniques than single organ transplant which can't bring satisfactory results to the patients.%目的 探讨肝肾联合移植的手术技术、治疗经验及疗效.方法 给2例肝炎后肝硬变、肝功能不全合并慢性肾功能衰竭患者施行一期肝肾联合移植.供体器官采用UW液原位灌洗,快速联合切取.肝移植采用原位肝移植技术,肾移植采用常规方法.术后免疫抑制治疗采用环孢素A、霉酚酸酯、抗淋巴细胞球蛋白和激素联合应用.分别于术后50 d和40 d开始服用抗乙型肝炎病毒药物拉米呋啶.结果 例1移植器官立即发挥功能,术后110 d移植肾发

  18. The characters of infections after heart transplantation: prevention and management%心脏移植受者术后感染特点及防治策略

    Institute of Scientific and Technical Information of China (English)

    赖颢; 张文平; 陈昊; 杨守国; 朱仕杰; 王春生

    2010-01-01

    Objective To explore the incidence and etiology of infection after heart transplantation and discuss the prophylaxis and management. Methods Retrospective study was conducted on the 140 survival heart transplant recipients (HTs) with detail follow-up information. All patients received preventive therapy against bacterial infections postoperatively, of which 87. 8% patients used antiviral drugs to prevent cytomegalovirus (CMV) infection. The immuosuppressive regiment was as follows: tacrolimus (Tac) or cyclosporine A (CsA), mycophenolate mofetil (MMF),glucocorticoid. Postoperatively all patients had throat swabs, sputum smear Gram stain, sputum culture, blood culture, urine culture and fecal culture for microbiological monitoring. Schedule tables were made to record and analyze the demography of the patients and the timetable of infections. Results The incidence of infections was 42.9 episodes per 100 HTs. Sixty-four cases (76. 2% ) of the infections occurred in the first month after transplantation and all recovered, 20 cases (23.8%) took place after 1 months, and 4 patients died. Conclusion Perioperative infections are mostly caused by bacteria and the prognosis is good. Infections 2 months after operation are commonly caused by virus or fungi with poor prognosis.%目的 探讨心脏移植受者术后感染的特点及相应的防治策略.方法 回顾性研究规律随访的140例心脏移植受者的病史资料.术后患者均接受抗细菌感染的预防性治疗,其中87.8%的患者术后以抗病毒药物预防巨细胞病毒感染.患者的免疫抑制方案为他克莫司或环孢素A+吗替麦考酚酯+糖皮质激素.术后患者行咽拭子、痰涂片革兰染色、痰培养、血培养、尿培养和粪培养进行微生物监测,统计感染时间及病原体等资料.结果 心脏移植受者感染发生率为42.9%(60/140),随访期间共发生感染84例次,64例次(76.2%)发生在术后第1个月内,均治愈;20例次(23.8%)发生于2

  19. New scoring system identifies kidney outcome with radiation therapy in acute renal allograft rejection

    International Nuclear Information System (INIS)

    Chen, Luci M.; Godinez, Juan; Thisted, Ronald A.; Woodle, E. Steve; Thistlewaite, J. Richard; Powers, Claire; Haraf, Daniel

    2000-01-01

    Purpose: To evaluate the role of radiation therapy for acute refractory renal rejection after failure of medical intervention, and to identify risk factors that influence graft survival following radiation therapy. Methods: Between June 1989 and December 1995, 53 renal transplant recipients (34 men and 19 women) were treated with localized radiation therapy for acute renal allograft rejection. Graft rejection was defined as an increase in serum creatinine with histologic evidence of rejection on renal biopsy. Ninety-one percent were cadaveric transplant recipients. The majority of patients who experienced acute graft rejection initially received corticosteroid therapy, except for 25% who were referred for radiation therapy and steroids for the first rejection. In more recent years, patients with moderate or severe steroid-resistant or recurrent rejection received OKT3, a polyclonal antilymphocyte antibody (ATGAM), tacrolimus (FK506), or mycophenolate mofetil (MMF). Patients who failed to respond to medical treatment were then referred for radiation therapy. Ultrasound was performed for kidney localization. Treatment consisted of a dose of 600 cGy given in 3 or 4 fractions using 6 MV photons, delivered AP or AP/PA. Results: The overall actuarial graft survival from the initiation of RT was 83% at 1 month, 60% at 1 year, and 36% at 5 years. The median follow-up from the date of transplant to the last follow-up was 22 months. The median time from the date of transplant to the initiation of radiotherapy was 3 months, and the median time from the initiation of radiotherapy to the last follow-up was 10 months. Variables evaluated were as follows: human leukocyte antigen matching on HLA-A, HLA-B, and HLA-DR, the transplant panel-reactive antibodies (PRA) at transplantation, number of acute rejection episodes, interval from the date of the transplant to the first rejection, serum creatinine levels at the time of the first radiation treatment, number of transplants, and

  20. Efficacy of total lymphoid irradiation for chronic allograft rejection following double lung transplantation

    International Nuclear Information System (INIS)

    Diamond, David A.; Michalski, Jeff M.; Trulock, Elbert M.; Lynch, John P.

    1997-01-01

    Purpose: The purpose of this study was to assess the safety and efficacy of total lymphoid irradiation in a series of patients experiencing chronic rejection following bilateral lung transplantation. Patients and Materials: Eleven patients (10 males, 1 female) received total lymphoid irradiation for chronic allograft rejection (bronchiolitis obliterans syndrome) refractory to conventional treatment modalities. Treatment was delivered between March, 1995, and September, 1996. Mean patient age was 33 years (range 15-51). Indications for transplantation included cystic fibrosis (7 patients), alpha 1 anti-trypsin deficiency (2 patients), primary pulmonary hypertension (1 patient), and emphysema (1 patient). Radiation therapy was prescribed as 800 cGy delivered in ten 80 cGy fractions, 2 fractions per week, via AP/PA mantle and inverted-Y fields. Radiation was withheld for total wbc count 3 , absolute neutrophil count 3 , or platelets 3 . Serial pre- and post-radiation therapy pulmonary function values, complete blood counts, and immunosuppressive augmentation requirements (use of methylprednisolone, azathioprine, mycophenolate mofetil, OKT3, and FK506) were monitored. Results: In the 3 months preceding total lymphoid irradiation, the average decrease in FEV 1 was 34% (range 0-75%) and the median number of immunosuppression augmentations was 3 (range 0-5). At initiation of radiation therapy, the average FEV 1 was 1.4 liters (range 0.77-2.28). Only (4(11)) patients completed all 10 treatment fractions. Reasons for discontinuation included unabated rejection (4 patients), worsening pulmonary infection (2 patients), and persistent thrombocytopenia (1 patient). No treatment course was discontinued because of persistent neutropenia or leukopenia. Seven of the 11 patients failed within 8 weeks of treatment cessation. One patient had unabated rejection and received bilateral living related donor transplants. He is alive and well. Six patients died. Two of these deaths were due

  1. [The role of core decompression for the treatment of femoral head avascular necrosis in renal transplant recipients].

    Science.gov (United States)

    Zivcić-Cosić, Stela; Stalekar, Hrvoje; Mamula, Mihaela; Miletić, Damir; Orlić, Lidija; Racki, Sanjin; Cicvarić, Tedi

    2012-10-01

    Avascular bone necrosis is a relatively rare but significant complication in renal transplant recipients because it causes progressive pain and invalidity. It can be the consequence of the action of numerous causative factors, but it is mostly connected to corticosteroid treatment.The underlying pathophysiologic mechanism is a diminished blood flow to the bone leading to necrosis and bone destruction. During the past 25-years period, 570 renal transplantations and five combined kidney and pancreas transplantations were performed in our centre. A part of the patients was lost to follow-up due to the separation of Croatia from the former Republic of Yugoslavia. After transplantation, we revealed aseptic necrosis of the femoral head in five female patients. All patients had a history of treatment with pulse doses of corticosteroids. At transplantation the average age of the patients was 52.2 yrs (range 46 to 62 yrs), and dialytic treatment before transplantation lasted in average 9.2 yrs (range 2.5 to 21.2 yrs). The period between renal transplantation and the development of clinical signs of avascular bone necrosis lasted in average 1.2 yrs (range 0.3 to 2.3 yrs). We will demonstrate our 62-year old female patient with terminal renal failure caused by post-streptococcal glomerulonephritis, who was treated with peritoneal dialysis 2.5 years before renal transplantation. Twenty months before renal transplantation the patient received pulse doses of corticosteroids, together with immunoglobulins and plasmapheresis, for the treatment of an acute polyradiculoneuritis Guillaine Barré. After transplantation a standard immunosuppressive protocol was applied which included tacrolimus, mycophenolate mofetil, corticosteroids and induction with basiliximab. Four months after transplantation the patient started to feel pain in the right hip after longer standing, in addition to the earlier long-lasting problems caused by bilateral coxarthrosis. The pelvic radiograph showed

  2. AUTOIMMUNE EPIDERMAL BLISTERING DISEASES

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    Ana Maria Abreu Velez

    2013-11-01

    ABDs is based on histology of lesional skin and direct immunofluorescence (DIF of perilesional skin, as well as by serologic confirmation of autoantibodies by indirect immunofluorescence (IIF and recombinant autoantigens. The titers of the autoantibodies may correlate with the disease severity, and can be measured by indirect immunofluorescence and by ELISA testing. Therapeutically, systemic treatment with glucocorticoids is combined with immunosuppressive adjuvants which allow for fast reduction of systemic steroids. A prospective clinical trial in pemphigus showed that adjuvant treatment with azathioprine, mycophenolate mofetil and cyclophosphamide led to a significant reduction of the cumulative dose of systemic steroids until complete clinical remission was achieved. In bullous pemphigoid, topical treatment with clobetasol can help to accomplish a clinical remission without the major side effects seen with systemic steroids. Also, therapeutic depletion of B lymphocytes by rituximab has considerably improved the overall prognosis of pemphigus. Nurses and other paramedical personal caring for patients with these disorders play a critical role in improving the quality of life of the patients and their families. The patients need to be continuously evaluated to avoid secondary infections, especially if they have long term immuosupressive treatment.

  3. Radiation therapy treatment of acute refractory renal allograft rejection

    International Nuclear Information System (INIS)

    Godinez, J.; Thisted, R.A.; Woodle, E.S.; Thistlethwaite, J.R.; Powers, C.; Haraf, D.

    1996-01-01

    Purpose: To evaluate the impact of the use of radiotherapy to preserve the renal graft in patients with recurrent graft rejection that failed to respond to medical treatment and identify risk factors to predict the probability of graft loss. Material and Methods: Between June 1989 and December 1995, 53 renal graft recipients were treated at our institution after experiencing several episodes of rejection. Rejection was defined as an unexplained, consecutive, daily rise in serum creatinine. Each episode was confirmed with renal biopsy. Patients who experienced rejection were initially treated with solu medrol bolus and prednisone. Patients with steroid-resistant or recurrent rejection received OKT3, polyclonal antilymphocyte antibody, FK506, or mycophenolate mofetil. Those who failed to respond to medical treatment were referred for radiotherapy. Treatment consisted of a dose of 600 cGy given in 3 or 4 fractions using 6 MV photons, AP or AP/PA. All patients underwent ultrasound kidney localization; a 2 cm margin was given around the kidney. Results: Median follow-up from the date of transplant to the last follow-up was 22 months (range 1-83 months), the median time from the date of transplant to the initiation of radiotherapy was 3 months, and the median time from the initiation of radiotherapy to the last follow up was 10 months (range 0.1 to 64 months). Of these 34 men and 19 women, median age of 3), Ninety-one percent were cadaveric transplant recipients., human leukocyte antigen matching on HLA-A and HLA-B (zero antigens in 26 patients/one or two shared antigens in 27 patients), HLA-DR locus (zero antigens in 34 patients/one or two shared antigens in 19 patients), transplant panel-reactive antibodies at transplantation (median PRA-Curr of 3% and median PRA-Max of 8%), number of acute rejection episodes, interval from the date of the transplant to the first rejection (median 1 month, range 5 days to 68 months), serum creatinine levels at the time of the first

  4. Persistent hypertension and progressive renal injury induced by salt overload after short term nitric oxide inhibition Hipertensão persistente e lesão renal progressiva induzidas por sobrecarga de sal após inibição temporária do óxido nítrico

    Directory of Open Access Journals (Sweden)

    Ana Lúcia Mattar

    2007-01-01

    Full Text Available INTRODUCTION: Administration of the NO inhibitor Nwð-nitro-L-arginine methyl ester (NAME and a high-salt diet (HS promotes severe albuminuria and renal injury, which regresses upon discontinuation of treatments. OBJECTIVE: We investigated whether these changes reappear after reinstitution of HS, and whether they are prevented by treatment with the antilymphocyte agent mycophenolate mofetil (MMF or the AT-1 receptor blocker losartan (L. Adult male Munich-Wistar rats received NAME and HS. A control Group (C received only HS. After 20 days, rats receiving HS and NAME exhibited severe hypertension and albuminuria. After a 30-day recovery period, hypertension was attenuated and albuminuria had virtually disappeared. MATERIAL AND METHODS: Rats were then distributed among the following groups: HS, receiving HS; NS, receiving a normal salt (NS diet; HS-MMF, receiving HS and MMF; HS-LOS, receiving HS and L; HS-HDZ, receiving HS and hydralazine (HDZ. Sixty days later, NS rats showed only slight albuminuria and renal damage or inflammation. In contrast, HS rats developed severe hypertension, marked glomerulosclerosis with interstitial expansion and renal infiltration by macrophages and angiotensin II-positive cells. The group treated with losartan had lowered blood pressure and a lack of albuminuria or renal injury. MMF provided similar protection without altering blood pressure, suggesting a nonhemodynamic effect, a hypothesis reinforced by the finding that HDZ lowered blood pressure without preventing renal injury. RESULTS: These results indicate that treatment with HS and NAME predisposes to the development of hypertension and renal injury upon salt overload, characterizing a new model of chronic nephropathy. CONCLUSION: The response to MMF or L, but not HDZ, suggests a key role for inflammatory rather than hemodynamic factors.INTRODUÇÃO: A administração de Nômega-nitro-L-arginina metiléster (NAME, um inibidor da produção de NO, com dieta rica

  5. Lung and renal transplantation

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    Patrícia Caetano Mota

    2009-11-01

    Full Text Available Renal transplantation is the most common type of solid organ transplantation and kidney transplant recipients are susceptible to pulmonary complications of immunosuppressive therapy, which are a diagnostic and therapeutic challenge. Aim: To evaluate patients admitted to the Renal Transplant Unit (RTU of Hospital de S. João with respiratory disease. Subject and methods: We performed a retrospective study of all patients admitted to RTU with respiratory disease during a period of 12 months. Results: Thirty-six patients were included. Mean age 55.2 ( ± 13.4 years; 61.1% male. Immunosuppressive agents most frequently used were prednisolone and mycophenolate mofetil associated with ciclosporin (38.9% or tacrolimus (22.2% or rapamycin (13.9%. Thirty-one patients (86.1% presented infectious respiratory disease. In this group the main diagnoses were 23 (74.2% pneumonias, 5 (16.1% opportunistic infections, 2 (6.5% tracheobronchitis, and 1 case (3.2% of lung abscesses. Microbiological agent was identified in 7 cases (22.6%. Five patients (13.9% presented rapamycin-induced lung disease. Fibreoptic bronchoscopy was performed in 15 patients (41.7%, diagnostic in 10 cases (66.7%. Mean hospital stay was 17.1 ( ± 18.5 days and no related death was observed. Conclusion: Respiratory infections were the main complications in these patients. Drug-induced lung disease implies recognition of its features and a rigorous monitoring of drug serum levels. A more invasive diagnostic approach was determinant in the choice of an early and more specific therapy. Resumo: O transplante renal é o transplante de órgãos sólidos mais frequente, sendo os transplantados renais alvo de complicações pulmonares inerentes à própria terapêutica imunossupressora, as quais constituem, por vezes, um desafio diagnóstico e terapêutico. Objectivo: Avaliar os doentes admitidos na Unidade de Transplante Renal (UTR do Hospital de S. João com o diagnóstico de patologia respirat

  6. Pulmão e transplante renal

    Directory of Open Access Journals (Sweden)

    Patrícia Caetano Mota

    2009-11-01

    complications of immunosuppressive therapy, which are a diagnostic and therapeutic challenge.Aim: To evaluate patients admitted to the Renal Transplant Unit (RTU of Hospital de S. João with respiratory disease.Subject and methods: We performed a retrospective study of all patients admitted to RTU with respiratory disease during a period of 12 months.Results: Thirty-six patients were included. Mean age 55.2 (±13.4 years; 61.1% male. Immunosuppressive agents most frequently used were prednisolone and mycophenolate mofetil associated with ciclosporin (38.9% or tacrolimus (22.2% or rapamycin (13.9%. Thirty-one patients (86.1% presented infectious respiratory disease. In this group the main diagnoses were 23 (74.2% pneumonias, 5 (16.1% opportunistic infections, 2 (6.5% tracheobronchitis, and 1 case (3.2% of lung abscesses. Microbiological agent was identified in 7 cases (22.6%. Five patients (13.9% presented rapamycin-induced lung disease. Fibreoptic bronchoscopy was performed in 15 patients (41.7%, diagnostic in 10 cases (66.7%. Mean hospital stay was 17.1 (±18.5 days and no related death was observed.Conclusion: Respiratory infections were the main complications in these patients. Drug-induced lung disease implies recognition of its features and a rigorous monitoring of drug serum levels. A more invasive diagnostic approach was determinant in the choice of an early and more specific therapy.Rev Port Pneumol 2009; XV (6: 1073-1099 Palavras-chave: Pulmão, transplante renal, imunossupressão, Key-words: Lung, renal transplantation, immunosuppression

  7. Pulmão e transplante renal Lung and renal transplantation

    Directory of Open Access Journals (Sweden)

    Patrícia Caetano Mota

    2009-11-01

    diagnostic and therapeutic challenge. Aim: To evaluate patients admitted to the Renal Transplant Unit (RTU of Hospital de S. João with respiratory disease. Subject and methods: We performed a retrospective study of all patients admitted to RTU with respiratory disease during a period of 12 months. Results: Thirty-six patients were included. Mean age 55.2 (±13.4 years; 61.1% male. Immunosuppressive agents most frequently used were prednisolone and mycophenolate mofetil associated with ciclosporin (38.9% or tacrolimus (22.2% or rapamycin (13.9%. Thirty-one patients (86.1% presented infectious respiratory disease. In this group the main diagnoses were 23 (74.2% pneumonias, 5 (16.1% opportunistic infections, 2 (6.5% tracheobronchitis, and 1 case (3.2% of lung abscesses. Microbiological agent was identified in 7 cases (22.6%. Five patients (13.9% presented rapamycin-induced lung disease. Fibreoptic bronchoscopy was performed in 15 patients (41.7%, diagnostic in 10 cases (66.7%. Mean hospital stay was 17.1 (±18.5 days and no related death was observed. Conclusion: Respiratory infections were the main complications in these patients. Drug-induced lung disease implies recognition of its features and a rigorous monitoring of drug serum levels. A more invasive diagnostic approach was determinant in the choice of an early and more specific therapy.

  8. Experiência com transplante cardíaco heterotópico em pacientes com resistência pulmonar elevada: seguimento tardio Experiencia con trasplante cardíaco heterotópico en pacientes con resistencia pulmonar elevada: seguimiento tardío Experience with heterotopic heart transplantation in patients with elevated pulmonary vascular resistance: late follow-up

    Directory of Open Access Journals (Sweden)

    Jose Henrique Andrade Vila

    2010-02-01

    este tipo de alternativa, para pacientes seleccionados.BACKGROUND: Along the past few years the number of papers on heterotopic cardiac transplant has been very scarce in the medical literature, including at the international level; this is particularly true in reference to the long term follow-up of these patients and the reason which led to the presentation of our report. OBJECTIVE: To report the initial clinical experience and late evolution of 4 patients undergoing heterotopic heart transplantation, indications for this procedure and its major complications. METHODS: The surgeries were performed between 1992 and 2001, and all had as indication for heterotopic transplantation the PVR, which ranged from 4.8 WU to 6.5WU, with a transpulmonary gradient above 15mmHg. In the 3rd patient, a direct anastomosis between the pulmonary arteries was performed without the use of a prostetic tube, and a mitral valvuloplasty and a LV aneurysmectomy were performed in the native heart. The immediate immunosuppressive regimens were double, with cyclosporine and azathioprine in the first 3 patients, and cyclosporine and mycophenolate mofetil in the 4th patient. RESULTS: One immediate death occurred from graft failure, one death occurred after 2 ½ years, from endocarditis in an intraventricular thrombus in the native heart, and a third death occurred 6 years after transplantation, from post-operative complications of the aortic valve surgery in the native heart. The remaining patient is well, 15 years after the transplantation. This patient is in functional class II (NYHA, 6 years after a surgical occlusion of the native heart aortic valve. CONCLUSION: Heterotopic heart transplantation results are inferior to those of orthotopic heart transplantation because they present higher RVP. The intraventricular thrombi, in the native heart, which require prolonged anticoagulation, and aortic valve complications, also in the native heart, may require surgical treatment. However, a patient's 15

  9. Download this PDF file

    African Journals Online (AJOL)

    ...

    THE PREVALENCE OF SIDE-EFFECTS: CIPROFLOXACIN 500 MG SINGLE DOSE PRO-. PHYLAXIS AGAINST .... Provincial and Local Health Authorities, World Health. Organisation .... Leucopoenia, eosinophilia and mild elevations in se-.

  10. of aspirin The use of renal enzymes indication of renal toxicity dose ...

    African Journals Online (AJOL)

    1983-04-30

    Apr 30, 1983 ... analysis revealed that aspirin significantly increased the output of both ... Acetylsalicylic acid (Disprin) I500 mg wa administered 3 times a day .... completely removing salicylic acid and metabolites from the urine, as could be ...

  11. The role of phytohormone on the production of berberine in the calli ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-09-17

    Sep 17, 2008 ... Available online at http://www.academicjournals.org/AJB .... The air dried calli culture (500 mg) was homogenized with a mortar and pestle then extracted ... solution of Dragendroff's reagent was then added which gave brick.

  12. 21 CFR 520.2200 - Sulfachlorpyridazine.

    Science.gov (United States)

    2010-04-01

    ... after the last treatment. (3) Dogs—(i) Amount. Administer tablets orally at 500 mg per 10 to 15 lb of... caused by other Gram-positive and Gram-negative organisms that are susceptible to sulfonamide therapy...

  13. Use of Fourier Transform Infrared (FTIR) spectroscopy to study cadmium-induced changes in Padina tetrastromatica (Hauck)

    Digital Repository Service at National Institute of Oceanography (India)

    DeSouza, L.; PrabhaDevi; DivyaShridhar, M.P.; Naik, C.G.

    and stored in a vacuum desiccator in airtight containers until further analysis. Analysis for metal concentration Known weight (500 mg dry weight) of both control and cadmium treated dried algal powder was digested in Tefl on bombs in nitric acid...

  14. Pharmacokinetics of Caffeic Acid from Methanol Seed Extract of ...

    African Journals Online (AJOL)

    Methods: A dose of the extract (500 mg, equivalent to 37.135 mg caffeic acid) was administered orally to 6 male .... emission. Validation studies. Linearity. The rat plasma samples were spiked by caffeic acid solutions ..... Atomic structure of.

  15. The pharmacokinetics of artemisinin after administration of two different suppositories to healthy Vietnamese subjects

    NARCIS (Netherlands)

    Koopmans, R.; Ha, L. D.; Duc, D. D.; Dien, T. K.; Kager, P. A.; Khanh, N. X.; van Boxtel, C. J.; de Vries, P. J.

    1999-01-01

    Eight healthy Vietnamese male subjects received 400 mg artemisinin formulated into fatty suppositories (FS), and six different subjects received 500 mg of artemisinin formulated in polyethylene glycol suppositories (PEGS). Plasma concentrations were measured by high-performance liquid chromatography

  16. single dose pharmacokinetics of mefloquine in healthy nigerian

    African Journals Online (AJOL)

    BSN

    Mefloquine 500mg single dose was administered and blood samples were collected ... particle size ODS Hypersil (HETP, Macclesfield, UK) at a pressure of 55 Mpa .... dose to area under the plasma drug concentration - time curve, assuming ...

  17. Lupus Nephritis in Asia: Clinical Features and Management.

    Science.gov (United States)

    Yap, Desmond Y H; Chan, Tak Mao

    2015-09-01

    outcomes in Asian patients with LN compare favorably with patients from other parts of the world. The prevention and treatment of infective complications remain significant challenges in managing LN in Asia. (1) The prevalence of SLE is lower among Caucasians than other ethnicities. A higher prevalence is observed among Asians and African Americans, while the highest prevalence is found in Caribbean people. The prevalence of LN in Asian SLE patients is much higher than in Caucasians as well. However, the 10-year renal outcome and renal survival rate appear to be better in Asians. (2) Polymorphisms of genes involved in the immune response, such as Fcγ receptor, integrin alpha M, TNF superfamily 4, myotubularin-related protein 3 and many others, might be partly responsible for the differences in prevalence between the different ethnic groups. European ancestry was shown to be associated with a decrease in the risk of LN even after adjustment for genes most associated with renal disease. (3) Access to health care is a key determinant of disease progression, treatment outcome and the management of complications such as infections, particularly in South Asia, and might also explain disparities between clinical outcomes. (4) The efficacy of low-dose CYC combined with corticosteroids for induction treatment of LN was proved in European Caucasian patients. This treatment is also used in Asia, although no formal evaluation of efficacy and safety in comparison with other treatment regimens exists in this population. The efficacy of mycophenolate mofetil (MMF) is similar to that of CYC, and similar between Asians and Caucasians. MMF may be more effective than CYC in inducing response in high-risk populations such as African American or Hispanic patients. MMF might cause less infection-related events in Asians, but its high cost prevents broader usage at present. (5) For maintenance therapy, corticosteroid combined with AZA or MMF is used worldwide, with a broadly similar efficacy of

  18. feeding value of processed horse eye bean meal as alternative ...

    African Journals Online (AJOL)

    PROF. BARTH EKWEME

    ; Vitamin D3 2,000000I.U; Vitamin E 20,000IU; Vitamin K 2,250mg; Thiamine 1,750mg;. Riboflavin B 5,000mg; Pyridoxine B6 2,750mg; Anti oxidant 125g; Niacin 27,500mg; Vitamin B12 15mg; Panthotenic acids 7,500mg; Biotin 50mg; Choline ...

  19. Optic nerve oxygen tension

    DEFF Research Database (Denmark)

    la Cour, M; Kiilgaard, Jens Folke; Eysteinsson, T

    2000-01-01

    To investigate the influence of acute changes in intraocular pressure on the oxygen tension in the vicinity of the optic nerve head under control conditions and after intravenous administration of 500 mg of the carbonic anhydrase inhibitor dorzolamide.......To investigate the influence of acute changes in intraocular pressure on the oxygen tension in the vicinity of the optic nerve head under control conditions and after intravenous administration of 500 mg of the carbonic anhydrase inhibitor dorzolamide....

  20. Protective Effect of Free and Bound Polyphenol Extracts from Ginger (Zingiber officinale Roscoe) on the Hepatic Antioxidant and Some Carbohydrate Metabolizing Enzymes of Streptozotocin-Induced Diabetic Rats

    OpenAIRE

    Kazeem, Mutiu Idowu; Akanji, Musbau Adewunmi; Yakubu, Musa Toyin; Ashafa, Anofi Omotayo Tom

    2013-01-01

    This study investigated the hepatoprotective effects of polyphenols from Zingiber officinale on streptozotocin-induced diabetic rats by assessing liver antioxidant enzymes, carbohydrate-metabolizing enzymes and liver function indices. Initial oral glucose tolerance test was conducted using 125?mg/kg, 250?mg/kg, and 500?mg/kg body weight of both free and bound polyphenols from Z. officinale. 28 day daily oral administration of 500?mg/kg body weight of free and bound polyphenols from Z. officin...

  1. Cerebroprotective prevention of memory disorders using sodium valproate

    Directory of Open Access Journals (Sweden)

    A. V. Ivanov

    2013-04-01

    Full Text Available Epilepsy is the disease resulting in impaired cognitive function. The paper deals with the use of nootropics against the background of an anticonvulsant effect. Results of experiments on rats showed that investigated nootropics piracetam (500 mg/kg, citicoline (500 mg/kg, memantine (10 mg/kg in combination with sodium valproate (80 mg/kg improve memory and do not change its anticonvulsant effect.

  2. Fontes de potássio no crescimento in vitro de plantas de orquídea Cattleya loddigesii Potassium sources of Cattleya loddigesii plants in vitro growth

    Directory of Open Access Journals (Sweden)

    Milene Alves de Figueiredo

    2008-02-01

    Full Text Available Plantas de Cattleya loddigesii com 1,0-1,5cm de comprimento, oriundas de sementes germinadas in vitro, foram inoculadas nos tratamentos, os quais consistiram da adição de diferentes concentrações de cloreto e sulfato de potássio (ambos a 0, 125, 250, 375 e 500mg L-1 ao meio Knudson C, em todas as combinações possíveis, acrescido de 2g L-1 de carvão ativado e 150g L-1 de polpa de banana "Nanica". O meio teve seu pH ajustado para 5,8±0,1 e foi solidificado com 5g L-1 de ágar antes da autoclavagem a 121°C por 20 minutos. Após a inoculação, as culturas foram mantidas por 90 dias em sala de crescimento com irradiância em torno de 35µmol m-2 s-1, temperatura de 25±1°C e fotoperíodo de 16 horas. A combinação de 500mg L-1 de KCl com 500mg L-1 de K2SO4 promoveu maior crescimento in vitro em plantas de Cattleya loddigesii, exceto no comprimento de raízes, que se apresentou melhor com 500mg L-1 de KCl na ausência de K2SO4.Cattleya loddigesii preceding seedlings (with 1.0-1.5cm of in vitro germinated seeds were used as explants. The treatments consisted of the addition of different potassium chloride concentrations (0; 125; 250; 375 e 500mg L-1 and potassium sulphate (0; 125; 250; 375 e 500mg L-1, in the Knudson C medium, in all possible combinations, an addition of 2g L-1 activated coal, 150g L-1 and banana 'Nanica' pulp. The medium had the pH set to 5.8±0.1 and was solidified with agar 5g L-1 before the sterilization at 121°C for 20 minutes. After the inoculation, the cultures were maintained in the growth room with irradiancy around 35µmol m-2 s-1 in, 25±1°C temperature and 16-hour photoperiod for 90 days. The combination of KCl 500mg L-1 with K2SO4 500mg L-1 promotes good in vitro growth in Cattleya loddigesii seedlings, except length of roots who if comported better with KCl500 mg L-1 in absence of K2SO4.

  3. Future immunosuppressive agents in solid-organ transplantation.

    Science.gov (United States)

    Gabardi, Steven; Cerio, Jeffrey

    2004-06-01

    To review the pharmacology, pharmacokinetics, efficacy, and safety of mycophenolate sodium, everolimus, and FTY720. Clinical trials and abstracts evaluating mycophenolate sodium, everolimus, and FTY720 in solid-organ transplantation were considered for evaluation. English-language studies and published abstracts were selected for inclusion. Mycophenolate sodium has recently been approved by the Food and Drug Adminstration for marketing in the United States; everolimus and FTY720 are immunosuppressive agents that may soon be available in the United States. These agents have proven efficacy in reducing the incidence of acute rejection in solid-organ transplantation. Clinical trials have shown that these newer agents are relatively well tolerated. The most common adverse events associated with these agents were gastrointestinal and hematologic effects (mycophenolate sodium); hyperlipidemia, increased serum creatinine, and hematologic effects (everolimus): and gastrointestinal effects, headache, and bradycardia (FTY720). Mycophenolate sodium has been approved in some European countries and the United States. Everolimus has been approved in some European countries and a new drug application has been submitted to the Food and Drug Administration. FTY720 is currently in phase III clinical trials and submission to the Food and Drug Administration for approval is a few years away. The approval of these agents will furnish the transplant practitioner with even more options for immunosuppression.

  4. Preliminary pharmacological screening of Bixa orellana L. leaves.

    Science.gov (United States)

    Shilpi, Jamil Ahmad; Taufiq-Ur-Rahman, Md; Uddin, Shaikh Jamal; Alam, Md Shahanur; Sadhu, Samir Kumar; Seidel, Véronique

    2006-11-24

    Preliminary pharmacological studies were performed on the methanol extract of Bixa orellana L. (Bixaceae) leaves to investigate neuropharmacological, anticonvulsant, analgesic, antidiarrhoeal activity and effect on gastrointestinal motility. All studies were conducted in mice using doses of 125, 250 and 500 mg/kg of body weight. In the pentobarbitone-induced hypnosis test, the extract statistically reduced the time for the onset of sleep at 500 mg/kg dose and (dose-dependently) increased the total sleeping time at 250 and 500 mg/kg dose. A statistically significant decrease in locomotor activity was observed at all doses in the open-field and hole-cross tests. In the strychnine-induced anticonvulsant test, the extract increased the average survival time of the test animals (statistically significant at 250 and 500 mg/kg). The extract significantly and dose-dependently reduced the writhing reflex in the acetic acid-induced writhing test. Antidiarrhoeal activity was supported by a statistically significant decrease in the total number of stools (including wet stools) in castor oil-induced diarrhoea model. A statistically significant delay in the passage of charcoal meal was observed at 500 mg/kg in the gastrointestinal motility test. The extract was further evaluated in vitro for antioxidant and antibacterial activity. It revealed radical scavenging properties in the DPPH assay (IC(50)=22.36 microg/ml) and antibacterial activity against selected causative agents of diarrhoea and dysentery, including Shigella dysenteriae.

  5. Screening of the antimalarial activity of plants of the Cucurbitaceae family

    Directory of Open Access Journals (Sweden)

    Cláudia Zuany Amorim

    1991-01-01

    Full Text Available Crude ethanolic extracts (CEEs from two species of Cucurbitaceae, Cucurbita maxima and Momordica charantia (commonly called "abóbora moranga" and melão de São Caetano", respectively were assayed for antimalarial activity by the 4-d suppressive test. The CEE of dry C. maxima seeds showed strong antimalarial activity following oral administration (259 and 500 mg/kg, reducing by 50% the levels of parasistemia in Plasmodium berghey-infected mice. Treatment of normal animals with 500 mg/Kg of the extract three days before intravenous injection of P. berghei caused a significant 30% reduction in parasitemic levels. No effect was observed when the animals were treated with the CEE only on the day of inoculation. Oral administration of the CEE of dry M. charantia leaves adminstered orally was ineffective up to 500 mg/Kg in lowering the parasitemic levels of malarious mice.

  6. Malaria chemoprophylaxis in travellers to east Africa: a comparative prospective study of chloroquine plus proguanil with chloroquine plus sulfadoxine-pyrimethamine

    DEFF Research Database (Denmark)

    Fogh, S; Schapira, A; Bygbjerg, Ib Christian

    1988-01-01

    As malaria caused by Plasmodium falciparum has become resistant to chloroquine alternative drug regimens need to be developed. The prophylactic efficacy against malaria and the side effects of chloroquine phosphate 500 mg weekly with proguanil hydrochloride 200 mg daily was compared...... with the efficacy of chloroquine 500 mg weekly with sulfadoxine 500 mg-pyrimethamine 25 mg weekly in a randomised study of Scandinavian travellers to Kenya and Tanzania during 1984-5. A total of 767 subjects (416 male and 351 female; 384 taking chloroquine phosphate with proguanil hydrochloride and 383 taking...... chloroquine with sulfadoxine-pyrimethamine) completed a diary on the breakthrough of malaria and the side effects of treatment while taking the drugs. They were also asked to make thick blood films when symptoms like those of malaria occurred, which were sent to and analysed in Denmark. Four subjects taking...

  7. Antioxidant and Hepatoprotective Effects of Methanolic Extracts of Zilla spinosa and Hammada elegans Against Carbon Tetrachlorideinduced Hepatotoxicity in Rats

    Directory of Open Access Journals (Sweden)

    Ullah Riaz

    2018-03-01

    Full Text Available The detoxification, metabolism, and excretion of various endogenous and exogenous materials occur mainly in the liver. Liver diseases are a global concern, and classified as chronic hepatitis, cirrhosis, and hepatosis. The development of safe hepatoprotective agents remains an unmet need. Therefore, we investigated the antioxidant effects of methanolic and n-hexane fractions of Zilla spinosa (ZSM and ZSH, respectively and Hammada elegans (HEM and HEH, respectively against carbon tetrachloride (CCl4-induced liver toxicity in rats. Antioxidant activity was studied by the 2,2-diphenyl-1-picrylhydrazyl (DPPH assay. The rats were divided into 11 groups (n=6–group, 1 (control, group 2 (CCl4 only, group 3 (CCl4+silymarin 10 mg/kg, group 4 (CCl4+HEM 250 mg/kg, group 5 (CC14+HEM 500 mg/kg, group 6 (CCl4+HEH 250 mg/kg, group, 7 (CCl4+HEH 500 mg/kg, group, 8 (CCl4+ZSM 250 mg/kg, group 9 (CCl4+ZSM 500 mg/kg, group 10 (CCl4+ZSH 250 mg/kg, and group 11 (CCl4+ZSH 500 mg/kg. Serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transferase, and total bilirubin were measured. The extent of hepatic injury was histopathologically assessed. Treatment with ZSM and ZSH at 250 and 500 mg/kg did not significantly affect biochemical results compared with the CCl4 only group. However, treatment with both HEM and HEH at 250 and 500 mg/kg provided significant (p<0.001 results compared with the CCl4 only group. These results were consistent with histological findings. HEM and HEH at 250 μg/mL significantly inhibited DPPH radical formation by 38.E6 and 35.65%, rerpectively. However antioxidant effects of ZSM and ZSH were insignificant.

  8. Effects of exogenous glutathione and cysteine on growth, lead accumulation, and tolerance of Iris lactea var. chinensis.

    Science.gov (United States)

    Yuan, Haiyan; Zhang, Yongxia; Huang, Suzhen; Yang, Yongheng; Gu, Chunsun

    2015-02-01

    Effects of exogenous reduced glutathione (GSH) and cysteine (Cys) on growth, lead (Pb) accumulation, and nonprotein thiol (NPT) contents of Iris lactea var. chinensis under 100 and 500 mg L(-1) Pb stress were studied. Our results showed that 500 mg L(-1) Pb stress caused a dramatical decline in fresh weights, while the reduction of aboveground biomass was alleviated by exogenous GSH and Cys even though keeping higher Pb contents in roots and shoots. Exogenous GSH and Cys could enhance Pb accumulation in the shoots and roots compared with single Pb treatment. The promoting effect of GSH to Pb accumulation was larger than the effect of Cys, and the Pb contents in the shoots and roots treated with 500 mg L(-1) Pb + GSH reached 1,712 and 14,603 mg kg(-1), about 4.19 and 2.78 times of single 500 mg L(-1) Pb treatment, respectively. Microscopic imaging of Pb in roots and leaves showed that higher intensive fluorescence was observed in cell wall of root epidermis, stele, vascular tissues of the roots, and sclerenchyma cells of leaves treated with 500 mg L(-1) Pb + GSH and treated with 500 mg L(-1) Pb + Cys. Exogenous GSH had an apparent promoting effect on root and shoot GSH synthesis, while exogenous Cys reduced the synthesis of cellular GSH in shoot and increased Cys contents. Pb only induced the synthesis of phytochelatin (PC)2 in roots, and the PC2 content declined in GSH- and Cys-treated plant roots. These results suggested that GSH synthesis was a more effective approach to improve Pb accumulation and translocation of I. lactea var. chinensis. Further analysis of protein expression in plants by exogenous GSH and buthionine sulfoximine (BSO) application showed that the proteins regulated by GSH and BSO may constitute various enzymes involved in GSH biosynthesis and play certain roles in Pb accumulation and tolerance of I. lactea var. chinensis.

  9. Sensory-motor axonal polyneuropathy involving cranial nerves: An uncommon manifestation of disulfiram toxicity.

    Science.gov (United States)

    Santos, Telma; Martins Campos, António; Morais, Hugo

    2017-01-01

    Disulfiram (tetraethylthiuram disulfide) has been used for the treatment of alcohol dependence. An axonal sensory-motor polyneuropathy with involvement of cranial pairs due to disulfiram is exceedingly rare. The authors report a unique case of an extremely severe axonal polyneuropathy involving cranial nerves that developed within weeks after a regular dosage of 500mg/day disulfiram. To the authors best knowledge, such a severe and rapidly-progressive course has never been described with disulfiram dosages of only 500mg/day. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Efeito da Gymnema sylvestre na elevação da lipidemia após administração de gordura de origem animal em ratos wistar - DOI: 10.4025/actascibiolsci.v26i3.1602 The influence of Gymnema sylvestre on the elevation of blood levels of lipids after administration of animal fat in male wistar rats - DOI: 10.4025/actascibiolsci.v26i3.1602

    Directory of Open Access Journals (Sweden)

    Márcia Regina Batista

    2004-04-01

    Full Text Available Neste trabalho investigamos a influência da Gymnema sylvestre (Gs na elevação da lipidemia após administração de gordura de origem animal em ratos machos Wistar (230g - 250g. Os animais, em jejum por 22 horas, foram divididos em 5 grupos que receberam via intragástrica às 8h os seguintes tratamentos: 1 2mL de gordura suína Batavo®/kg de peso corpóreo (GSB; 2 GSB + 500mg/kg de peso corpóreo de Gs (Gs 500mg; 3 GSB + 1g/kg de peso corpóreo de Gs (Gs 1g; 4 Gs 500mg; 5 Gs 1g. Os animais foram sacrificados 30min após a administração destas substâncias. Não observamos diferenças significativas na concentração sérica de lipídeos totais, triglicerídeos e colesterol total nos ratos que receberam GSB na ausência ou presença de Gs 500mg ou Gs 1g. Portanto, nossos resultados sugerem que a Gs não afeta a absorção intestinal de lipídeosThe aim of the present experiment was to investigate the influence of Gymnema sylvestre (Gs on the elevation of blood levels of lipids after administration of animal fat in male Wistar rats (230–250g. The animals, which were fasted for 22h, were separated in five groups that received (8:00 a.m intragastric administration of: 1 2ml of pork fat Batavo® /kg of body weight (PFB; 2 PFB+500mg/kg of Gs body weight (Gs 500mg; 3 PFB + 1g/kg of Gs body weight (Gs 1 g; 4 Gs 500mg; 5 Gs 1g. The animals were sacrificed 30min after the administration of these substances. No significant differences were verified in the serum concentration of total lipids, triglycerides and cholesterol in the animals, which received PBF in the presence or absence of Gs 500mg or Gs 1g. Therefore, the results showed that Gs could not affect the intestinal absorption of lipids

  11. Phase II study of Gleevec® plus hydroxyurea (HU) in adults with progressive or recurrent meningioma

    OpenAIRE

    Reardon, David A.; Norden, Andrew D.; Desjardins, Annick; Vredenburgh, James J.; Herndon, James E.; Coan, April; Sampson, John H.; Gururangan, Sridharan; Peters, Katherine B.; McLendon, Roger E.; Norfleet, Julie A.; Lipp, Eric S.; Drappatz, Jan; Wen, Patrick Y.; Friedman, Henry S.

    2011-01-01

    We prospectively evaluated the efficacy and safety of imatinib plus hydroxyurea in patients with progressive/recurrent meningioma. A total of 21 patients with progressive/recurrent meningioma were enrolled in this dual center, single-arm, phase II trial. All patients received 500 mg of hydroxyurea twice a day. Imatinib was administered at 400 mg/day for patients not on CYP3A enzyme inducing anti-epileptic drugs (EIAEDs) and at 500 mg twice a day for patients on EIAEDs. The primary endpoint wa...

  12. Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma

    OpenAIRE

    Reardon, D A; Dresemann, G; Taillibert, S; Campone, M; van den Bent, M; Clement, P; Blomquist, E; Gordower, L; Schultz, H; Raizer, J; Hau, P; Easaw, J; Gil, M; Tonn, J; Gijtenbeek, A

    2009-01-01

    textabstractBackground: We evaluated the efficacy of imatinib mesylate in addition to hydroxyurea in patients with recurrent glioblastoma (GBM) who were either on or not on enzyme-inducing anti-epileptic drugs (EIAEDs). Methods: A total of 231 patients with GBM at first recurrence from 21 institutions in 10 countries were enrolled. All patients received 500 mg of hydroxyurea twice a day. Imatinib was administered at 600 mg per day for patients not on EIAEDs and at 500 mg twice a day if on EIA...

  13. Treating chancroid: summary of studies in southern Africa.

    Science.gov (United States)

    Ballard, R C; Duncan, M O; Fehler, H G; Dangor, Y; Exposto, F L; Latif, A S

    1989-01-01

    Recent studies undertaken in southern Africa and elsewhere indicate that many short or single dose treatments are available to treat chancroid. Erythromycin 500 mg three times a day for five days, ciprofloxacin 500 mg, sulphamethopyrazine 800 mg and trimethoprim 1000 mg or sulphametrole 3200 mg and trimethoprim 640 mg as single oral doses, or ceftriaxone 250 mg as a single intramuscular injection are all effective in treating the disease. The widespread use of these regimens largely depends on the accuracy of diagnosis, susceptibilities of local Haemophilus ducreyi isolates to antimicrobials, and financial considerations. PMID:2629710

  14. Effect of aminoethoxyvinylglycine on biochemical, physicomechanical and colour properties of cv. Braeburn applesEfeito da aminoetoxivinilglicina nas propriedades físico-mecânicas, bioquímicas e cor da maçã cv. Braeburn

    Directory of Open Access Journals (Sweden)

    Burhan Ozturk

    2013-06-01

    Full Text Available Foram determinados os efeitos do tratamento em pré-colheita com aminoetoxivinilglicina (AVG nas propriedades bioquímicas, físico-mecânicas e características da cor da maçã ‘Braeburn’. AVG foi aplicado quatro semanas antes da data estimada de colheita, em quatro doses (0, 100, 300 e 500 mgL- 1. Enquanto os menores valores de sólidos solúveis totais e pH foram obtidos no tratamento com 500 mgL-1 AVG, os maiores valores foram obtidos no tratamento com 0 mgL-1 AVG. A acidez titulável foi maior no tratamento com 500 mgL-1 AVG do que nos tratamentos 100 e 300 mgL-1. A maior atividade de fenólicos totais e antioxidantes na polpa e na casca da maçã foi obtida no tratamento com 0 mgL-1 AVG, enquanto que o menor valor foi obtido no tratamento com 500 mgL-1 AVG. Com o aumento das doses de AVG, a antocianina monomérica total foi reduzida. As médias geométricas diâmetro do fruto, massa do fruto, força de remoção de frutas, polpa e casca aumentaram com o aumento das doses de AVG. Os valores do ângulo da matriz de polpa e casca da fruta foram menores no tratamento com 0 mgL-1 AVG.The effect of preharvest AVG (aminoethoxyvinylglycine treatments on the biochemical, physicomechanical properties and colour characteristics of cv. Braeburn apples were determined. AVG was applied in four different doses (0, 100, 300 and 500 mgL-1 AVG 4 weeks before the estimated harvest date. While the lowest values of total soluble solid content and pH were obtained from 500 mgL-1 AVG treatment, the highest values were obtained from control. The titratable acidity was higher in 500 mgL-1 AVG treatment than those of the 100 and 300 mgL-1 AVG treatments. The highest total phenolic and antioxidant activity of both flesh and skin apple was obtained from control, whereas lowest value was obtained from 500 mgL-1 AVG treatment. With increasing doses of AVG, the total monomeric anthocyanin was reduced. The geometric means: fruit diameter, fruit mass, fruit removal

  15. Efficacy of single and double doses of albendazole and mebendazole alone and in combination in the treatment of Trichuris trichiura in school-age children in Uganda

    DEFF Research Database (Denmark)

    Namwanje, Harriet; Kabatereine, Narcis B.; Olsen, Annette

    2011-01-01

    A randomised clinical trial was conducted in Kabale District, southwestern Uganda, to compare the efficacies of single and double doses of a combination of 400mg albendazole (ALB) and 500mg mebendazole (MBZ) with those of single and double doses of each drug given alone in the treatment of Trichu......A randomised clinical trial was conducted in Kabale District, southwestern Uganda, to compare the efficacies of single and double doses of a combination of 400mg albendazole (ALB) and 500mg mebendazole (MBZ) with those of single and double doses of each drug given alone in the treatment...

  16. 非血缘关系造血干细胞移植61例分析%Clinical retrospective analysis of 61 cases of unrelated donor hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    方峻; 洪梅; 夏凌辉; 游泳; 黎纬明; 刘芳; 汪玉芳; 毛星宁; 邹萍

    2009-01-01

    Objective To study the therapeutic effectiveness, associated complications and related factors of unrelated allogeneic hematopoietic stem cell transplantation (URD-HSCT). Methods Sixty-one patients with malignant hematological diseases received URD-HSCT. All cases were subjected to myeloablative or nonmyeloablative conditioning regimen according to primary diseases. Among 61 patients, 21 were donor-recipient 6/6 HLA-matched, 5 were 5/6 HLA antigen-matched, 24 were 1 HLA gene subtype-mismatched, 11 were 2 HLA gene subtype-mismatched. Eighteen patients were ABO-compatible with donors, while 43 ABO-incompatible with donors. The median of infused donor nucleated cells was 4.5×108/kg, and the median of CD34+ cells were 4.3×106/kg. The graft-versus-host disease (GVHD) prevention regimens were based on short-term MTX, cyclosporin A and mycophenolate mofetil (MMF) regimen. Forty-nine cases also received CD25 Mab on the day of transplantation, and the day 4 after transplantation. Nine cases were also administrated with antilymphocyte globulin (ALG) or antithymocyte globulin (ATG). Two cases received ALG and CD25 Mab. Results Among 61 patients, 59 cases were successfully engrafted, which was identified by blood type, chromosome test and DNA polymorphism. Twenty-three cases developed grade Ⅱ~Ⅳ acute GVHD. Twenty-five patients experienced chronic GVHD. Infection of bacterial and/or fungal within 100 days after URD-HSCT was documented in 48 cases. Thirty-six cases had cytomegalovirus infection. Major infection site was lower respiratory tract. Eighteen cases died after URD-HSCT, and the 2-year disease-free survival rate was (68.0±6.4)%. Among these 18 deaths, 12 cases died because of transplantation related complications with the transplantation related mortality (TRM) being 19.7 %, and the remaining 6 cases died of relapse with the relapse rate being 9. 8 %, respectively. Conclusions URD-HSCT is an effective therapeutic strategy for malignant hematopoietic diseases

  17. [Treatment of Gaucher disease with allogeneic hematopoietic stem cell transplantation: report of three cases and review of literatures].

    Science.gov (United States)

    Tang, Xiangfeng; Luan, Zuo; Wu, Nanhai; Zhang, Bo; Jing, Yuanfang; Du, Hong; Lu, Wei; Xu, Shixia

    2015-11-01

    To explore the efficacy of unrelated umbilical cord blood transplantation (UCBT) in the treatment of Gaucher disease. The clinical characteristics of three children with Gaucher disease underwent UCBT in our hospital between April 2013 and September 2014 were retrospectively analyzed. Literature on allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of Gaucher disease was searched at Wanfang and Pubmed databases between 1983 and 2015 and was reviewed and summaried. Three children with Gaucher disease, all were female, received UCBT. These patients' age at receiving transplantation was 3.8 years, 7.1 years and 2.6 years, respectively. The second case received the second transplantation. The first and third case received splenectomy before UCBT. The pretreatment regimen was busulfan (Bu)/fludarabine (Flu)/cyclophosphamide (CTX)/antithymocyte globulin (ATG), and for the patient received the second transplantation melphalan was added to the myeloablative conditioning regimen of Bu/Flu/CTX/ATG. Cyclosporine and mycophenolate mofetil (MMF) wee used for prophylaxis of acute graft versus host disease (aGVHD). The dose of cord blood stem cell nucleated cell counts was 9.7 × 10⁷ /kg,11.9 × 10⁷ /kg and 7.6 × 10⁷/kg respectively. The dose of cord blood stem cell CD34⁺ cell counts was 5.4 × 10⁵/kg , 3.5 × 10⁵/kg and 3.2 × 10⁵/kg respectively. The day of granulocytes exceeding 0.5 × 10⁹/L was day 11, 12 and 19 after transplantation, respectively. The day of platelets exceeding 20 × 10⁹/L was day 14, 33 and 74 after transplantation, respectively. At one month after transplantation the rate of chimerism was over 95% and all patients got donor complete chimerism. The level of β-glucocerebrosidase recovered to normal at one month after transplantation. During transplantation, all patients developed cytomegalovirus (CMV) and Epstein-Barr virus (EBV) viremia. In case 1 immune thrombocytopenia occurred at five month after

  18. Examinations of Factors Influencing Survival of Liver Transplantation for Hepatocellular Carcinoma: A Single-Center Experience From Budapest.

    Science.gov (United States)

    Piros, L; Fehérvári, I; Görög, D; Nemes, B; Szabó, J; Gerlei, Z; Végső, G; Kóbori, L; Máthé, Z

    2015-09-01

    Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide. Orthotopic liver transplantation (OLT) is the best therapy of choice for early, unresectable HCC. The Hungarian Liver Transplantation Program was launched in 1995 at the Department of Transplantation and Surgery, Semmelweis University, Budapest. From that time more than 60 patients underwent OLT for hepatic tumors, which in most cases were HCC. Our clinical examination was undertaken to analyze the possible influential factors of outcomes for our series of patients who received OLT for HCC. We performed a review of all patients who underwent OLT for HCC at our department from 1996 to October 1, 2013. Disease extent was determined by preoperative computed tomography or magnetic resonance images. All explants were examined and categorized based on tumor number, size, distribution, HCC histologic grade, and vascular invasion. Patients with HCC were classified as having tumors either meeting Milan criteria, beyond Milan criteria but within UCSF criteria, or exceeding UCSF criteria. OLT was performed using standard techniques including orthotopic implantation with cross-clamp technique or with the piggyback technique. Postoperative immunosuppression included a triple drug regimen of calcineurin inhibitor (CNI), mycophenolate mofetil (MMF), and prednisone. mTOR inhibitors have been available since 2004. HCC most commonly occurs in the presence of cirrhosis as a result of longstanding chronic liver disease. Most of our patients who underwent OLT for HCC are 56 to 60 years old, and most also had underlying HCV cirrhosis. As of October 1, 2013, 21 of 49 (42.85%) patients had died after OLT for HCC. The main cause was the recurrence of the HCC in 38%, followed by sepsis in 33%, and HCV recurrence in 19%. One death each (4.7% of the total number of deaths) was caused by primary nonfunction of the graft, acute myocardial infarct, and de novo malignancy, respectively. Overall

  19. CLINICAL VALUE OF BAFF AND APRIL CONCENTRATIONS IN SYSTEMIC LUPUS ERYTHEMATOSUS

    Directory of Open Access Journals (Sweden)

    T. A. Panafidina

    2016-01-01

    Full Text Available Systemic lupus erythematosus (SLE is characterized by the pathological activation and differentiation of B lymphocytes. The B-lymphocyte stimulator (BLyS, also known as B cell-activating factor of the tumor necrosis factor family (BAFF, and its homologue, a proliferation-inducing ligand (APRIL, belong to the ligands of the tumor necrosis factor (TNF family and play a key role in B-lymphocyte selection and survival.Objective: to determine serum BAFF and APRIL concentrations in patients with SLE and a relationship of the clinical and laboratory parameters of the disease to the level of these cytokines.Subjects and methods. The investigation enrolled 73 patients (62 women and 11 men; median age, 30.0 [28.0; 46.0] years with SLE (disease duration, 5.0 [1.5; 11.0] years and its high activity (the median SLEDAI-2K scores of 8 [2; 13].Involvement of the kidneys and joints were found in 40 and 36% of cases, respectively; there were hematologic disorders in 38%, antinuclear factor (ANF in 94.5%, and anti-double stranded DNA antibodies in 77%. The concurrent antiphospholipid syndrome was detected in 15% of the patients. 66% of the patients took glucocorticoids (GCs (the median dose was 10 [0; 15] mg/day, calculated with reference to prednisolone, 42% received cytotoxic drugs (cyclophosphamide, mycophenolate mofetil, azathioprine; 12% used biological agents (BAs; 31.5% received no therapy at enrolment in the investigation. Serum BAFF and APRIL concentrations were estimated using an enzyme immunoassay.Results and discussion. The concentrations of BAFF and APRIL did not differ essentially in the patients with SLE and in the controls: the median level of BAFF was 0.02 [0.01; 0.64] and 0.02 [0.01; 0.03] ng/ml; that of APRIL was 2.09 [0.01; 3.80] and 0.01 [0.01; 4.16] ng/ml, respectively. The elevated concentration of BAFF (>0.82 ng/ml was revealed in 5.5% of the patients with SLE and that of APRIL (>5.96 ng/ml in 4.1%. There was a positive correlation between

  20. Living unrelated donor kidney transplantation between spouses%夫妻间活体供肾移植

    Institute of Scientific and Technical Information of China (English)

    王凯; 曲青山; 苗书斋

    2011-01-01

    BACKGROUND: In recent years, with emergence of laws and regulations of organ transplantation one after another, rapid advance in organ transplantation has been made in China. In addition to cadaveric renal transplantation, the living donor kidney transplantation has been developed. Living unrelated donor kidney transplantation between spouses occupies an important position in the field of organ transplantation.OBJECTIVE: To observe the curative effects of living unrelated donor kidney transplantation between spouses. METHODS: 11 cases who received living unrelated donor kidney transplantation between spouses between October 2008 and September 2010 at Department of Organ Transplantation in People's Hospital of Zhengzhou and 83 cases who concurrently received cadaveric renal transplantation were included in this study. In each group, the recipients received end-to-side anastomosis between donor renal vein and external iliac vein, end-to-end anastomosis between donor renal artery and internal iliac artery, nipple-like anastomosis between ureter and bladder, and tunnel embedding. The immunosupprassive induction schert>e included methyliprednisolone and the triple-drug immunosuppressive therapy consisting of calcmeunn (tacrolimus or dclosporin), mycophenolate mofetil. And adrenal cortical hormone was used as basic immunosuppressive scheme. Trough concentration of drug-containing blood was adjusted according to tacrolimus or ciclosporin application dose. Follow up was performed within 6 months after transplantation. Renal function recovery and complications during the early stage after renal transplantation were evaluated.RESULTS AND CONCLUSION: Incidence of early complications including acute rejections and delayed function recovery of transplant was significantly lower in cases who received living unrelated donor kidney transplantation between spouses than in cases who received cadaveric renal transplantation (P < 0.05). These results indicate that living unrelated

  1. Metabolic differences of tacrolimus between patients with combined liver and kidney transplantation and patients with single liver or single kidney transplantation%他克莫司在肝肾联合移植患者与单纯肝移植及单纯肾移植患者之间代谢的差异

    Institute of Scientific and Technical Information of China (English)

    鲁燕侠; 邹德勇; 王新; 严莲珍

    2017-01-01

    目的 探讨他克莫司在不同器官移植受者间的代谢差异.方法 采用回顾性研究方法,选择武警总医院器官移植中心2002年1月至2012年8月收治的器官移植患者30例,分为肝肾联合移植(SLK)组、单纯肝移植组和单纯肾移植组,每组10例.SLK组与单纯肝移植组两组给药方案相同,术中均给予甲泼尼龙注射液,术后采用他克莫司+吗替麦考酚酯+泼尼松三联免疫抑制治疗方案.术后第1天给予他克莫司,初始剂量0.06 mg·kg-1·d-1,分2次服用,术后第3天开始检测他克莫司全血谷浓度;单纯肾移植组术后2~4 d给予他克莫司,初始剂量为0.15 mg·kg-1·d-1,分2次服用,服药3 d后开始监测他克莫司全血谷浓度.比较3组移植术后1个月内他克莫司的服药剂量和全血谷浓度.结果 术后1个月SLK组口服他克莫司剂量(μg·kg-1·d-1:74.78±32.65比80.62±24.02、85.58±16.78)及血药浓度监测值(μg/L:6.64±2.73比7.50±3.08、7.46±3.20)均低于单纯肝移植组和单纯肾移植组,但组间比较差异无统计学意义(均P>0.05).结论 SLK中移植肝对于移植肾的保护作用可能与术后时间有关.术后1个月内移植肝对于移植肾未显示出保护作用.%Objective To investigate the metabolic differences of Tacrolimus in different transplant recipients. Methods A retrospective study was conducted, 30 patients of the organ transplant admitted to organ transplantation center of General Hospital of Chinese People's Armed Police Forces from January 2002 to August 2012 were enrolled, and they were divided into combined liver and kidney transplant (SLK) group, single liver transplant group and single renal transplant group, 10 cases in each group. The SLK group and the simple liver transplantation group were given the same drug regimen, methylprednisolone injection was given during operation, and tacrolimus+ mycophenolate mofetil+ prednisone triple immunosuppressive therapy was taken after operation, on

  2. Yeast Interacting Proteins Database: YNL189W, YHR216W [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available g, expression is repressed by nutrient limitation Rows with this prey as prey (1) Rows with this prey as bai...osynthesis, expression is induced by mycophenolic acid resulting in resistance to the drug, expression is repressed by nutrient limit...ation Rows with this prey as prey Rows with this prey as

  3. Occurrence of immunosuppressive drugs and their metabolites in the sewage-impacted Vistula and Utrata Rivers and in tap water from the Warsaw region (Poland).

    Science.gov (United States)

    Giebułtowicz, Joanna; Nałęcz-Jawecki, Grzegorz

    2016-04-01

    Immunosuppresive therapy following organ transplant frequently includes treatment with tacrolimus and mycophenolic acid derivatives. These pharmaceuticals may enter the environment through wastewater treatment plant (WWTP) effluents and may have a potentially harmful effect on aquatic biota. Tacrolimus, mycophenolic acid and their metabolites were measured at specific points of a large Polish river (Vistula), a smaller river (Utrata) and in tap water samples from the Warsaw region. Analysis was performed using liquid chromatography tandem mass spectrometry, after solid phase extraction for water samples, or QuEChERS extraction for sediments. Residues of tacrolimus were below quantitation limits in both water and sediment samples. However, in water samples mycophenolic acid concentrations were measured at up to 180 ng L(-1) downstream of WWTP outfalls. No immunosuppressive drugs were detected in tap water. Concentrations of mycophenolic acid exceeded the predicted no effect concentration (PNEC) value in some Polish surface water, and risk calculations predicted at least twice higher concentrations in some other countries of the European Union. To the best of the authors' knowledge, this is the first report of these immunosuppressive drug concentrations in the environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Phylogeny of xerophilic aspergilli (subgenus Aspergillus and taxonomic revision of section Restricti

    Directory of Open Access Journals (Sweden)

    F. Sklenář

    2017-09-01

    The vast majority of species in sect. Restricti produce asperglaucide, asperphenamate or both in contrast to species in sect. Aspergillus. Mycophenolic acid was detected for the first time in at least six members of the section. The ascomata of A. halophilicus do not contain auroglaucin, epiheveadride or flavoglaucin which are common in sect. Aspergillus, but shares the echinulins with sect. Aspergillus.

  5. The influence of immunosuppressive drugs on neural stem/progenitor cell fate in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Skardelly, Marco, E-mail: Marco.Skardelly@med.uni-tuebingen.de [Department of Neurosurgery, University Hospital, Leipzig (Germany); Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig (Germany); Glien, Anja; Groba, Claudia; Schlichting, Nadine [Department of Neurosurgery, University Hospital, Leipzig (Germany); Kamprad, Manja [Institute of Clinical Immunology, Medical Faculty, University of Leipzig, Leipzig (Germany); Meixensberger, Juergen [Department of Neurosurgery, University Hospital, Leipzig (Germany); Milosevic, Javorina [Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig (Germany)

    2013-12-10

    In allogenic and xenogenic transplantation, adequate immunosuppression plays a major role in graft survival, especially over the long term. The effect of immunosuppressive drugs on neural stem/progenitor cell fate has not been sufficiently explored. The focus of this study is to systematically investigate the effects of the following four different immunotherapeutic strategies on human neural progenitor cell survival/death, proliferation, metabolic activity, differentiation and migration in vitro: (1) cyclosporine A (CsA), a calcineurin inhibitor; (2) everolimus (RAD001), an mTOR-inhibitor; (3) mycophenolic acid (MPA, mycophenolate), an inhibitor of inosine monophosphate dehydrogenase and (4) prednisolone, a steroid. At the minimum effective concentration (MEC), we found a prominent decrease in hNPCs' proliferative capacity (BrdU incorporation), especially for CsA and MPA, and an alteration of the NAD(P)H-dependent metabolic activity. Cell death rate, neurogenesis, gliogenesis and cell migration remained mostly unaffected under these conditions for all four immunosuppressants, except for apoptotic cell death, which was significantly increased by MPA treatment. - Highlights: • Four immunosuppresants (ISs) were tested in human neural progenitor cells in vitro. • Cyclosporine A and mycophenolic acid showed a prominent anti-proliferative activity • Mycophenolic acid exhibited a significant pro-apoptotic effect. • NAD(P)H-dependent metabolic activity was occasionally induced by ISs. • Neuronal differentiation and migration potential remained unaffected by ISs treatment.

  6. Early conversion from calcineurin inhibitor- to everolimus-based therapy following kidney transplantation : Results of the randomized ELEVATE trial

    NARCIS (Netherlands)

    de Fijter, Johan W; Holdaas, Hallvard; Øyen, Ole; Sanders, Jan Stephan; Sundar, Sankaran; Bemelman, Frederike J; Sommerer, Claudia; Pascual, Julio; Avihingsanon, Yingyos; Pongskul, Cholatip; Oppenheimer, Frederic; Toselli, Lorenzo; Russ, Graeme; Wang, Zailong; Lopez, Patricia; Kochuparampil, Jossy; Cruzado, Josep M; van der Giet, Markus

    In a 24-month, multicenter, open-label, randomized trial, 715 de novo kidney transplant recipients were randomized at 10-14 weeks to convert to everolimus (n=359) or remain on standard calcineurin inhibitor (CNI) therapy (n=356; 231 tacrolimus; 125 cyclosporine), all with mycophenolic acid and

  7. EFSA Panel on Dietetic Products, Nutrition, and Allergies (NDA); Scientific Opinion on the Tolerable Upper Intake Level of calcium

    DEFF Research Database (Denmark)

    Tetens, Inge

    Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to re-evaluate the safety in use of calcium. The Panel was requested to consider if the Tolerable Upper Intake Level (UL) for calcium established by the SCF in 2003 (2,500 mg...

  8. The role of the yeast as probiotic in protection against liver injury

    African Journals Online (AJOL)

    khairy

    cancer treatment (Chen et al., 2009). In this study, we ... animal food. The final yeast amount eaten by each rat/day was 500 mg/kg/day. Animals. Adult male Wistar albino rats, ageing approximately three months ..... collection of inflammatory cells and loss of hepatic tissue structural pattern; (d) treated with only yeast. CV,.

  9. Limited sampling strategy for determining metformin area under the plasma concentration-time curve

    DEFF Research Database (Denmark)

    Santoro, Ana Beatriz; Stage, Tore Bjerregaard; Struchiner, Claudio José

    2016-01-01

    AIM: The aim was to develop and validate limited sampling strategy (LSS) models to predict the area under the plasma concentration-time curve (AUC) for metformin. METHODS: Metformin plasma concentrations (n = 627) at 0-24 h after a single 500 mg dose were used for LSS development, based on all su...

  10. Evaluation of sorption capacity of adjusted woody biomass for pentavalent arsenic

    International Nuclear Information System (INIS)

    Littera, P.

    2009-01-01

    Aim of the present experiment was to evaluate the sorption capacity of wood biomass modified by iron oxyhydroxide. Capacity was assessed in tank experiments. Model solutions of pentavalent arsenic in concentration range of 20 mg L -1 -500 mg L -1 were used. Binder dosing 10 g L -1 was selected, contact time of the binder with solution was 2 hours. (author)

  11. Case report

    African Journals Online (AJOL)

    abp

    2014-08-04

    Aug 4, 2014 ... 1Intensive Care Unit, Department of Anesthesia and Intensive care, “A.H.E.P.A” University ... clindamycin 600mg q 6h i.v. and daptomycin 500mg q.d. i.v., ... (a synergistic interaction between microaerophilic nonhemolytic.

  12. 76 FR 33310 - Bristol-Myers Squibb Co. et al.; Withdrawal of Approval of 70 New Drug Applications and 97...

    Science.gov (United States)

    2011-06-08

    ... Promius Pharma, LLC, mononitrate) 200 Somerset Tablets, 20 mg. Corporate Blvd., 7th Floor, Bridgewater, NJ.... Suspension. NDA 050560 Cefizox (ceftizoxime Astellas Pharma US, sodium) Powder for Inc., 3 Parkway Injection... USP, EQ 500 mg (base) and 1 gram (g) (base) Vials. ANDA 063294 Cefizox (ceftizoxime Astellas Pharma US...

  13. Download this PDF file

    African Journals Online (AJOL)

    User

    involving administration of 250mg/kg, 500mg/kg and 1000mg/kg body weight of the ethyl acetate extract to the ... Unconjugated bilirubin levels in the test groups compared to the control. ... synthesize a wide variety of chemical compounds that.

  14. Efficacy and safety of various repeat treatment dosing regimens of rituximab in patients with active rheumatoid arthritis: results of a Phase III randomized study (MIRROR)

    NARCIS (Netherlands)

    Rubbert-Roth, Andrea; Tak, Paul P.; Zerbini, Cristiano; Tremblay, Jean-Luc; Carreño, Luis; Armstrong, Gillian; Collinson, Neil; Shaw, Tim M.

    2010-01-01

    Methods. Patients with active RA despite stable MTX (10-25 mg/week) were randomly assigned to one of the three treatment regimens comprising two courses of RTX given 24 weeks apart: 2 x 500 and 2 x 500 mg; 2 x 500 and 2 x 1000 mg (dose escalation); and 2 x 1000 and 2 x 1000 mg. The primary endpoint

  15. Concentration of trace metals in boreholes in the Ankobra Basin, Ghan

    African Journals Online (AJOL)

    Roughly 25% of the boreholes had manganese concentration higher than 500 mg l-1, which is the WHO maximum acceptable limit for drinking water. The concentration of mercury was higher than 1.0 mg l-1 (WHO maximum acceptable limit) in 60% of the boreholes during the rainy season but below detection limit in the dry ...

  16. Subacute toxicity experiment with rats fed a diet containing ergotaminetartrate. 1 General toxicology

    NARCIS (Netherlands)

    Speijers GJA; Krajnc-Franken MAM; van Leeuwen FXR; Danse LHJC; Loeber JG; Elvers LH; Hoejenbos-Spithout HHM; Janssen GB

    1992-01-01

    In this study reduced food intake, food efficiency and growth were noticed at dose levels of 100 mg EAT/kg diet and higher. Slight changes in the red blood parameters were seen in the 100 and 500 mg EAT/kg diet dose groups. Urea concentration was increased in the females of the highest dose group.

  17. Afican Health Sciences Vol 9 No 1.pmd

    African Journals Online (AJOL)

    Administrator

    African Health Sciences Vol 9 No 1 March 2009. 41 compounds isolated from the extracts can be applied as weed killers and have been tested on the water hyacinth .... dispensing serial dilutions of the test extract, concentrations ranging from 5.0 mg/ml to 50.0 mg/ ml. McFarland No.1 standard was used in the preparation ...

  18. SINGLE-DOSE VERSUS 3-DAY PROPHYLAXIS WITH CIPROFLOXACIN IN TRANSURETHRAL SURGERY - A CLINICAL-TRIAL

    NARCIS (Netherlands)

    BIJL, W; JANKNEGT, RA

    1993-01-01

    in 235 patients who underwent transurethral surgery, perioperative oral ciprofloxacin prophylaxis was given as a single dose 500 mg versus a 3-day regimen. Out of 180 evaluable patients, 84 received a single dose and 96 received a 3-day course. In the single dose prophylaxis group there were 5

  19. Neuropharmacological activities of the aqueous fraction of methanol ...

    African Journals Online (AJOL)

    aminopyridine-induced seizures. At all the doses tested (125-500 mg/kg), the fraction significantly (p < 0.05) reduced the number of head dips (in the hole board test), upward stairs climbed and rearings (in the stair case test). In the beam walking assay, ...

  20. The relationship between hippocampal EEG theta activity and locomotr behaviour in freely moving rats: effects of vigabatrin

    NARCIS (Netherlands)

    Bouwman, B.M.; Lier, H. van; Nitert, H.E.J.; Drinkenburg, W.H.I.M.; Coenen, A.M.L.; Rijn, C.M. van

    2005-01-01

    The relationship between hippocampal electroencephalogram (EEG) theta activity and locomotor speed in both spontaneous and forced walking conditions was studied in rats after vigabatrin injection (500 mg/kg i.p.). Vigabatrin increased the percentage of time that rats spent being immobile. During

  1. The use of renal enzymes as early indication of renal toxicity after ...

    African Journals Online (AJOL)

    Ten volunteers participated in a study comparing the effects on renal enzymes of multiple oral doses of aspirin relative to no treatment. The total urinary output was collected daily for 21 days from all subjects. The first 7 days were treatment-free. During the second 7-day period the subjects received aspirin 1 500 mg 3 times ...

  2. Double blind clinical trail comparing the safety and efficacy of ...

    African Journals Online (AJOL)

    Double blind clinical trail comparing the safety and efficacy of nimesulide (100g) and diclofenac in osteoarthrosis of the hip and knee joints. ... A significant proportion of the patients in the diclofenac group (50% vs 17.6%) had break through pain that warranted the use of at least two tablets of 500mg of paracetamol per week ...

  3. EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2013. Scientific Opinion on the safety of “citicoline” as a Novel Food ingredient

    DEFF Research Database (Denmark)

    Tetens, Inge

    level of 500 mg/day, and in foods for particular nutritional uses, specifically foods for special medical purposes, at a maximum level of 250 mg/serving, and with a maximum daily intake from these types of foods of 1 000 mg/day. Citicoline is readily hydrolysed on ingestion, breaking down to choline...

  4. original article candida species amongst pregnant women in benin

    African Journals Online (AJOL)

    Dr Oboro VO

    was used to streak Sabouraud Dextrose. Agar SDA (Oxoid, England) plates containing 0.5ml Chloramphenicol. (500mg,Pfizer) and incubated at 370C in triplicates. Uninoculated plain agar plates served as control for the inoculated ones. Discrete yeast colonies were subcultured on fresh SDA slants in. McCarthney bottles ...

  5. Pharmacological Investigation of Selected Medicinal Plants of ...

    African Journals Online (AJOL)

    noticeable decrease of exploratory behavior in the test animals from its initial value at 0 to 120 min (Table 2). The results were dose-dependent and significant at p < 0.05 level, At 30 min,. VNME (500 mg/ kg) and VNPE (250 mg/ kg) are significant compared to standard. At 60 min, all test samples are significant compared to.

  6. Dagelijkse opneming van nitraat, nitriet en vluchtige N-nitrosaminen, bepaald via analyse van duplicaat 24-uurs voedingen, bemonsterd in 1984/1985

    NARCIS (Netherlands)

    Ellen G; Egmond E; Sahertian ET

    1988-01-01

    Duplicaten van 24-uurs voedingen van 110 personen, bemonsterd in oktober 1984/maart 1985 werden geanalyseerd op gehalte aan nitraat, nitriet en vluchtige N-nitrosaminen. De gemeten gemiddelde nitraatopneming bedroeg 52 mg NO-3/etmaal, bereik 2-500 mg/etmaal. Nitriet was aantoonbaar, d.w.z.

  7. Phosphate-induced cadmium adsorption in a tropical savannah soil ...

    African Journals Online (AJOL)

    The influence of phosphate (P) on cadmium (Cd) adsorption was examined in a savanna soil with long history of different fertilizer amendment. The soil was incubated with P at 0, 250 and 500 mg P kg-1 soil and left to equilibrate for 2 weeks. Cd was added to the P-incubated soil at concentrations ranging from 27, 49 and ...

  8. Antidiuretic Activity of the Methanol Extract of Aporusa lindleyana ...

    African Journals Online (AJOL)

    several folk medicinal recipes in treatment of eye diseases, loose ... completely dry solid (79.98 g, 8.89 %) and weighed (Libror .... Table 2: Effect of oral administration of the methanol extract (ME) of Aporusa lindleyana (500 mg/kg) on some.

  9. Immunomodulatory activity of methanol extract of Adansonia digitata L

    African Journals Online (AJOL)

    Purpose: To evaluate the immune-modulatory activities of various plant parts Adansonia digitata L. using delayed-type hypersensitivity rat model. Methods: Defatted leaf, root bark and fruit pulp of A. digitata were extracted with methanol. Immunomodulatory activity of the methanol extracts (250 and 500 mg/kg) were ...

  10. Effect of vitamin C on salivary superoxide dismutase activity in ...

    African Journals Online (AJOL)

    In the first phase, patients of one group took 500 mg of vitamin C powder, for 3 weeks. Then saliva of all patients was collected. After a one- week wash-out period, vitamin C was given to the other group. Collection of saliva was done after 3 weeks. SOD activity was measured. Statistic evaluation was performed by Repeated ...

  11. An assessment of the quality of various brands of paracetamol ...

    African Journals Online (AJOL)

    To assess the seriousness of the global counterfeiting problem, we quantified the amount of active ingredient present in paracetamol tablets by various official and non-official methods. Eight brands of Paracetamol 500mg tablets were assessed using the quality control parameters of weight uniformity, active ingredient ...

  12. Effects of Satureja khuzistanica essential oils in drinking water on mortality, production performance, water intake, and organ weights in broiler chickens reared under heat stress condition.

    Science.gov (United States)

    Khosravinia, H

    2015-11-01

    An experiment was conducted to examine the effects on mortality, production performance, water intake (WI), and organ weight of Satureja khuzistanica essential oil (SkEO) using 720 1-day-old Arian broiler chicks in a 42-day trial. Experimental treatments were addition of 0 (control(-)), 200, 300, 400, and 500 mg/L SkEO or 500 mg/L polysorbate 80 (control(+)) into drinking water. The birds were kept under natural ambient temperatures 4 to 6 °C above standard recommendation from days 22 to 42 of age. Addition of SkEO into drinking water at 200 and 500 mg/L decreased weight gain (P  0.05). Supplementation of drinking water with 200, 300, 400, and 500 mg/L SkEO resulted in a 0.47, 4.40, 8.60, and 12.93% decrease in WI, respectively, from days 1 to 42 of age. The calculated European broiler index was greater for the birds received 400 mg/L of SkEO in their drinking water compared with that of the other birds (P water for heat-stressed broiler chickens improves economic efficiency possibly by promoting digestion process, creating miniscule improvement in FCR and lowered mortality rate.

  13. Grewia Gum 1: Some Mechanical and Swelling Properties of ...

    African Journals Online (AJOL)

    Purpose: To study the mechanical and dynamic swelling properties of grewia gum, evaluate its compression behaviour and determine the effect of drying methods on its properties. Methods: Compacts (500 mg) of both freeze-dried and air-dried grewia gum were separately prepared by compression on a potassium bromide ...

  14. Neuroprotective effect of Amorphophallus campanulatus in STZ ...

    African Journals Online (AJOL)

    3 mg/kg, ICV) day one and 3rd day after surgery. Surgery was performed on anesthetized rats by the help of stereotaxic apparatus. STZ induced AD rats were treated with petroleum ether extract of AC (100, 200 and 500 mg/kg, p.o.) for 14 days.

  15. Orbito-Maxillofacial Cutaneous Anthrax

    African Journals Online (AJOL)

    and development of a black eschar were reviewed. Occupational history, falls and/or contact with animal meat was ... and oral ciprofloxacin (500mg BD for 21 days). The culture results isolated Bacillus anthracis highly ... The clinical evolution of cutaneous anthrax is typical with the initial development of minute red macules.

  16. Maintenance Therapy With Cetuximab Every Second Week in the First-Line Treatment of Metastatic Colorectal Cancer

    DEFF Research Database (Denmark)

    Pfeiffer, Per; Sorbye, Hafdan; Qvortrup, Camilla

    2015-01-01

    Group performance status of 0 to 2. Patients received 8 courses of Nordic FLOX (oxaliplatin 85 mg/m(2) over 1 hour on day 1, and 5-fluorouracil 500 mg/m(2) as a bolus injection, followed 30 minutes later with bolus folinic acid 60 mg/m(2) on days 1 and 2). Cetuximab was administered every 2 weeks...

  17. 76 FR 14023 - Determination that ROCEPHIN (Ceftriaxone Sodium) Injection, 250 Milligrams, 500 Milligrams, 1...

    Science.gov (United States)

    2011-03-15

    ... 10 Grams Base/Vial, Approved Under New Drug Application 050585, Were Not Withdrawn From Sale for... milligrams (mg), 500mg, 1 gram (g), 2g, and 10g base/vial, approved under new drug application (NDA) 050585... active ingredient in the same strength and dosage form as the ``listed drug,'' which is a version of the...

  18. Scientific Opinion on taxifolin-rich extract from Dahurian Larch (Larix gmelinii)

    DEFF Research Database (Denmark)

    Sjödin, Anders Mikael

    2017-01-01

    to non-alcoholic beverages, to yogurt and to chocolate confectionery. The Panel considers that the data on genotoxicity do not raise concern. In a subchronic rat study performed in accordance with OECD standards, the highest dose tested (i.e. 1,500 mg/kg bw) was considered to be the NOAEL. The margin...

  19. The Effect Of Ocimum Gratissimum (Ram Tulsi) On Sexual ...

    African Journals Online (AJOL)

    The suspension of the extract of Ocimum gratissimum Linn. was administered orally at the dose of 100, 250, and 500 mg / kg body weight, to different groups of male rats (n = 6) once a day for seven days. The female Swiss Albino mice involved in mating were made receptive by hormonal treatment. The general mating ...

  20. Pharmacological evaluation of Vernonia elaeagnifolia (Asteraceae ...

    African Journals Online (AJOL)

    Method: Qualitative phytochemical analysis of V. elaeagnifolia leaves was performed. Thirty healthy albino rabbits were divided into six ... was administered at 250 mg/kg and 500 mg/kg per oral. Lipid profile, hepatic enzymes and oxidative ... from local market of Faisalabad, Pakistan. The rabbits were kept in iron cages at ...