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Sample records for mycophenolate mofetil treatment

  1. Successful treatment of severe refractory lupus hepatitis with mycophenolate mofetil.

    PubMed

    Tagawa, Y; Saito, T; Takada, K; Kawahata, K; Kohsaka, H

    2016-04-01

    Systemic lupus erythematosus-related hepatitis, known as lupus hepatitis, is a rare manifestation of systemic lupus erythematosus, and is usually subclinical with mild abnormalities of serum liver enzymes. While cases with clinically significant and refractory lupus hepatitis are uncommon, treatment options for lupus hepatitis are to be established. Here, we report the case of a 45-year-old man with progressive lupus hepatitis accompanied by autoimmune haemolytic anaemia. Lupus hepatitis of this patient was refractory to tacrolimus, azathioprine and cyclophosphamide, but was successfully treated by mycophenolate mofetil. Mycophenolate mofetil might be an effective therapeutic option for refractory lupus hepatitis.

  2. Mycophenolate mofetil in the treatment of systemic lupus erythematosus.

    PubMed

    Sahin, Ali

    2009-12-01

    Mycophenolate mofetil (MMF) is an immunosuppressive agent that has been shown to be effective in transplant patients. It is also efficacious in the management of lupus nephritis and useful in the treatment of autoimmune conditions because its mechanisms of action target T- and B- lymphocytes, leading to suppression of the cell-mediated immune response and antibody formation. MMF has been used successfully to treat immune-mediated conditions like myasthenia gravis, autoimmune hepatitis and immune cytopenias. However, the conditions for its optimal use for non-renal manifestations (e.g., hematological, neuropsychiatric, myocardial, pulmonary or cutaneous symptoms) in lupus patients are unclear. There have yet to be any randomized, controlled trials to guide the optimal dose and duration of MMF treatment in such situations. MMF is well tolerated and safe to use, although there are reports of serious adverse effects including urticaria, myopathy, Epstein-Barr virus-associated B-cell lymphoma, cytomegalovirus infection and disseminated varicella zoster infection. Immunosuppressive treatment with MMF and supportive care over the past few decades have led to improved clinical outcomes in patients with severe lupus nephritis. A favorable long-term prognosis can be ensured provided that effective treatment is instituted early, before irreversible renal parenchymal damage occurs. Another area of concern for patients is the increased cost of long-term MMF use.

  3. Mycophenolate mofetil versus azathioprine for maintenance treatment of lupus nephritis.

    PubMed

    Kaballo, Babikir G; Ahmed, Ahmed Elias; Nur, Musa Mohammed; Khalid, Ismail Osman; Abu-Aisha, Hasan

    2016-01-01

    To compare the efficacy of mycophenolate mofetil (MMF) with that of azathioprine (AZA) drugs in the maintenance therapy of lupus nephritis (LN) patients, we studied 81 Sudanese patients with LN (32 in Class III, 34 in Class IV, and 15 in combined Class V + IV of the ISN/RPS 2003 Classification). All patients received induction therapy consisting of monthly intravenous pulse doses of cyclophosphamide (CYC) (500 mg/m 2 of body-surface area) for six months, plus three consecutive pulses of intravenous methylprednisolone 15 mg/kg/day of body weight (maximum 500 mg). Subsequently, 41 (50.6%) patients were randomized into a group that received oral MMF (22 mg/kg/day), and 40 (49.4%) patients randomized to a group that received oral AZA (2 mg/kg/day). All patients initially received oral prednisone (1 mg/kg of body weight daily) for four weeks. The baseline characteristics of the two groups were similar. Total remission rate was 75.3% (80.5% in MMF and 70% in AZA), complete remission rate of 54.3% (56.1% with MMF and 52.5% with AZA), and a partial remission rate of 21% (24.4% with MMF and 17.5% with AZA) over 29 months. During maintenance therapy, six patients died (four in the AZA group and two in the MMF group), and end-stage renal disease (ESRD) developed in five patients (three in the AZA group and two in the MMF group). During the 36-months of the study, both groups had comparable event-free survival rate for the composite end point of death or ESRD and rate of relapse-free survival. Furthermore, both groups had no significant differences in terms of frequency of hospitalization, amenorrhea, infection, nausea, and vomiting. We conclude that our study showed that short-term therapy with intravenous CYC followed by maintenance therapy with oral MMF or AZA had similar efficacy and safety for the treatment of patients with moderate to severe LN.

  4. Linear IgA/IgG bullous dermatosis: successful treatment with dapsone and mycophenolate mofetil.

    PubMed

    Passos, Leny; Rabelo, Renata Fernandes; Matsuo, Christiane; Santos, Mônica; Talhari, Sinesio; Talhari, Carolina

    2011-01-01

    A 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.

  5. Development of primary central nervous system lymphoma in a systemic lupus erythematosus patient after treatment with mycophenolate mofetil and review of the literature.

    PubMed

    Balci, M A; Pamuk, G E; Unlu, E; Usta, U; Pamuk, O N

    2017-01-01

    Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin lymphoma and four cases of PCNSL have previously been described in association with mycophenolate mofetil. We report the fifth case of PCNSL in a patient with lupus nephropathy while on mycophenolate mofetil treatment.

  6. Impairment of mycophenolate mofetil absorption by calcium polycarbophil.

    PubMed

    Kato, Ryuji; Ooi, Kazuya; Ikura-Mori, Megumi; Tsuchishita, Yoshimasa; Hashimoto, Hiroshi; Yoshimura, Hironori; Uenishi, Kohji; Kawai, Masayuki; Tanaka, Kazuhiko; Ueno, Kazuyuki

    2002-11-01

    The effect of calcium polycarbophil on the absorption of mycophenolate mofetil, an immunosuppressive agent, was evaluated in healthy subjects. In vitro studies were performed to further evaluate the mechanism of the potential interaction. In the in vitro study, the release of mycophenolate mofetil from a cellulose membrane in the presence or absence of metal cations was measured using the dissolution test procedure. In the in vivo study, a randomized crossover design with two phases was used. In one phase, 6 male healthy volunteers received 1000 mg of mycophenolate mofetil alone (treatment 1); in the other phase, they received 1000 mg of mycophenolate mofetil and 2400 mg of calcium polycarbophil fine granules concomitantly (treatment 2). They received 30 mg of lansoprazole for 5 days and, on the 6th day, received mycophenolate mofetil and 2400 mg of calcium polycarbophil fine granules concomitantly (treatment 3). The serum concentration of mycophenolic acid was measured by high-performance liquid chromatography. In the in vitro study, the release from a cellulose membrane in the presence of calcium or iron ions was slower than that in the absence of these metal ions. In the in vivo study, the AUC0-12 and C(max) in treatment 2 were less than those in treatment 1. About 50% and 25% decreases in AUC0-12 in treatment 2 and treatment 3 were observed compared with those in treatment 1, respectively. These findings suggest that when mycophenolate mofetil and calcium polycarbophil were coadministered concomitantly, a decrease in mycophenolate mofetil absorption was observed. Therefore, it appears clear that the concomitant administration of mycophenolate mofetil and calcium polycarbophil should be avoided.

  7. Pediatric Pemphigus Vulgaris: Durable Treatment Responses Achieved with Prednisone and Mycophenolate Mofetil (MMF)

    PubMed Central

    Baratta, Andrea; Camarillo, Diana; Papa, Christine; Treat, James R.; Payne, Aimee S.; Rozenber, Suzanne S.; Yan, Albert C.

    2013-01-01

    Pemphigus vulgaris (PV) is a chronic autoimmune blistering disease of the skin and mucous membranes. Most cases occur in adults; cases in children are rare. This report describes the clinical presentations and treatment responses of three children with PV, as confirmed according to histology and indirect immunofluorescence studies. In all three cases, oral prednisone used in conjunction with mycophenolate mofetil (MMF) resulted in complete clinical remission, during which all pharmacotherapy was successfully discontinued. Resolution of the skin and mucosal blistering tended to occur quickly with prednisone, and after initiation of treatment with MMF, discontinuation of all pharmacotherapy was achieved within a range of 10 to 30 months in the three patients. One patient experienced a recurrence of genital lesions 19 months after discontinuation of therapy, but the condition remitted within 2 weeks with topical corticosteroid therapy. At the time of this report, the duration of complete remission ranged from 6 to 19 months. In summary, combination therapy with prednisone and MMF for pediatric PV appears to be a safe and effective approach that is associated with durable remission. PMID:22747679

  8. Pediatric pemphigus vulgaris: durable treatment responses achieved with prednisone and mycophenolate mofetil (MMF).

    PubMed

    Baratta, Andrea; Camarillo, Diana; Papa, Christine; Treat, James R; Payne, Aimee S; Rozenber, Suzanne S; Yan, Albert C

    2013-01-01

    Pemphigus vulgaris (PV) is a chronic autoimmune blistering disease of the skin and mucous membranes. Most cases occur in adults; cases in children are rare. This report describes the clinical presentations and treatment responses of three children with PV, as confirmed according to histology and indirect immunofluorescence studies. In all three cases, oral prednisone used in conjunction with mycophenolate mofetil (MMF) resulted in complete clinical remission, during which all pharmacotherapy was successfully discontinued. Resolution of the skin and mucosal blistering tended to occur quickly with prednisone, and after initiation of treatment with MMF, discontinuation of all pharmacotherapy was achieved within a range of 10 to 30 months in the three patients. One patient experienced a recurrence of genital lesions 19 months after discontinuation of therapy, but the condition remitted within 2 weeks with topical corticosteroid therapy. At the time of this report, the duration of complete remission ranged from 6 to 19 months. In summary, combination therapy with prednisone and MMF for pediatric PV appears to be a safe and effective approach that is associated with durable remission.

  9. Mycophenolate mofetil inducing remission of lupus enteritis.

    PubMed

    Al Balushi, F; Humby, F; Mahto, A; Kelly, C; Jawad, A

    2012-04-01

    We report the case of a young woman with a background history of discoid lupus who presented with abdominal pain, vomiting and intermittent diarrhoea. Physical examination revealed tenderness in the right upper quadrant with a palpable right inguinal lymph node without any other clinical signs of active lupus. Laboratory investigations showed normal inflammatory markers, positive ANA and Anti-Ro antibodies, persistent hypocomplementemia and lymphopenia, CT showed marked bowel oedema involving the small and large bowel (halo sign) with massive ascites and moderate right-sided pleural effusion. Mantoux test, AFB and TB cultures were negative. A diagnosis of lupus enteritis was made and treatment with high-dose steroids was commenced with little improvement. Treatment with cyclophosphamide was discussed but declined by the patient. Mycophenolate mofetil was commenced and resulted in significant clinical and radiological resolution. To the best of the authors' knowledge this is the first report of the successful use of mycophenolate mofetil in inducing and maintaining remission in lupus enteritis.

  10. Long-term experience of mycophenolate mofetil for treatment of diffuse cutaneous systemic sclerosis

    PubMed Central

    Le, Elizabeth N; Wigley, Fredrick M; Shah, Ami A; Boin, Francesco; Hummers, Laura K

    2013-01-01

    Background Immunosuppressive therapy may potentially alter the natural disease course of scleroderma. There have been reports of using mycophenolate mofetil (MMF) for the treatment of scleroderma skin disease. Objective To analyse the experience of using MMF for the treatment of active diffuse cutaneous scleroderma. Methods The authors compared the change in mean modified Rodnan skin scores (mRSS) in an MMF cohort at baseline with scores at 3, 6, 9 and 12 months and with those of historical controls from a pooled analysis of three multicentre randomised clinical trials of recombinant human relaxin, d-penicillamine and oral bovine type I collagen. Results Improvement in mRSS after treatment with MMF compared with baseline was seen as early as 3 months and continued through the 12-month follow-up. The mRSS of the MMF cohort was not different from that of the historical controls at 6 months (MMF −3.05±7.4 vs relaxin −4.83±6.99, p=0.059), but was significantly lower at 12 months (MMF −7.59±10.1 vs d-penicillamine −2.47±8.6, p<0.001; collagen −3.4±7.12, p=0.002). General and muscle severity scores and quality of life measures also improved compared with baseline. Pulmonary function remained stable. Conclusions MMF may benefit skin disease in patients with diffuse scleroderma, but prospective studies are required to determine its role. PMID:21378404

  11. Mycophenolate mofetil (MMF) for the treatment of steroid-resistant idiopathic thrombocytopenic purpura.

    PubMed

    Hou, Ming; Peng, Jun; Shi, Yan; Zhang, Chunqing; Qin, Ping; Zhao, Chuanli; Ji, Xuebin; Wang, Xueyong; Zhang, Maohong

    2003-06-01

    The treatment of chronic idiopathic thrombocytopenic purpura (ITP) is difficult in those unresponsive to corticosteroids and/or splenectomy. We attempted to induce durable response in 21 patients with refractory ITP by applying mycophenolate mofetil (MMF) (1.5-2.0 g/d), a novel immunosuppressive agent. Overall response rate was 62% (13 of 21), including 24% (five of 21) in complete response (CR), 29% (six of 21) in partial response (PR), and 10% (two of 21) in minor response (MR). The response rates for non-splenectomized and splenectomized ITP patients were 64% (nine of 14) and 57% (four of seven), respectively (P > 0.05). 39% (five of 13) responders relapsed as a result of dose reduction or withdraw of MMF, and 61% (eight of 13) responders maintained their effectiveness for a median of 24 wk. Sustained response was observed in three patients in whom MMF was withdrawn. MMF was well tolerated with only slight nausea and diarrhea recorded in 3 of 21 cases. No premature withdrawal was found in this study. CD3+ peripheral blood mononuclear cells (PBMC) and CD19+ PBMC were significantly reduced 12 wk after MMF administration in the responders. Platelet-associated antibodies against glycoproteins GPIIb/IIIa were detected in 13 of 21 (62%) patients before MMF treatment, and antibody levels were significantly decreased in responders 12 wk after MMF administration. This suggested that MMF might correct the immunologic abnormalities underlying the destruction of circulating platelets in ITP. We conclude that MMF could be used as a second-line agent for the treatment of steroid-resistant ITP before or after splenectomy and thereby is worth of further evaluation in randomized studies.

  12. The efficacy of Mycophenolate mofetil for the treatment of Chinese Takayasu’s arteritis

    PubMed Central

    Li, Jing; Yang, Yunjiao; Zhao, Jiuliang; Li, Mengtao; Tian, Xinping; Zeng, Xiaofeng

    2016-01-01

    To investigate the therapeutic effect of mycophenolate mofetil(MMF) on Chinese Takayasu’s arteritis(TAK) patients. Thirty consecutive TAK outpatients were prospectively enrolled during 2013 to 2015. MMF combined with glucocorticoid was the primary treatment regimen. If clinical stable disease could not be reached, another traditional immunosuppressive agent could be added. All patients were evaluated and followed up every 3 months and vascular image studies by Doppler ultrasonography were repeated every 6 months. The effectiveness of MMF was defined as:(1) ESR < 20 mm/hr;(2) CRP < 10 mg/L or hs-CRP<3 mg/L;(3) stable or improved in vascular image studies;(4) clinical assessment is stable, improved or in remission;(5) the dosage of glucocorticoid could be tapered to less than 15 mg/day. ESR < 40 mm/hr, CRP < 20 mg/L or hs-CRP < 6 mg/L, but meet the other three criteria is defined as partial effectiveness. MMF alone combined with corticosteroid was effective in 12(40.0%) patients. When MMF combined with methotrexate less than 15 mg/week, the effective rate was 30.0%(9/30), including partial effective in 3 patients. When MMF combined with azathioprine 100–150 mg/day, the effective rate was 10.0%(3/30), including partial effective in 1 patient. Four patients withdrew due to side effects. Two patients failed to show response. The overall effective rate of therapy including MMF in treating TAK is 80%. PMID:27924855

  13. Effectiveness of mycophenolate mofetil in C3 glomerulonephritis.

    PubMed

    Rabasco, Cristina; Cavero, Teresa; Román, Elena; Rojas-Rivera, Jorge; Olea, Teresa; Espinosa, Mario; Cabello, Virginia; Fernández-Juarez, Gema; González, Fayna; Ávila, Ana; Baltar, José María; Díaz, Montserrat; Alegre, Raquel; Elías, Sandra; Antón, Monserrat; Frutos, Miguel Angel; Pobes, Alfonso; Blasco, Miguel; Martín, Francisco; Bernis, Carmen; Macías, Manuel; Barroso, Sergio; de Lorenzo, Alberto; Ariceta, Gema; López-Mendoza, Manuel; Rivas, Begoña; López-Revuelta, Katia; Campistol, José María; Mendizábal, Santiago; de Córdoba, Santiago Rodríguez; Praga, Manuel

    2015-11-01

    C3 glomerulonephritis is a clinicopathologic entity defined by the presence of isolated or dominant deposits of C3 on immunofluorescence. To explore the effect of immunosuppression on C3 glomerulonephritis, we studied a series of 60 patients in whom a complete registry of treatments was available over a median follow-up of 47 months. Twenty patients had not received immunosuppressive treatments. In the remaining 40 patients, 22 had been treated with corticosteroids plus mycophenolate mofetil while 18 were treated with other immunosuppressive regimens (corticosteroids alone or corticosteroids plus cyclophosphamide). The number of patients developing end-stage renal disease was significantly lower among treated compared with untreated patients (3 vs. 7 patients, respectively). No patient in the corticosteroids plus mycophenolate mofetil group doubled serum creatinine nor developed end-stage renal disease, as compared with 7 (significant) and 3 (not significant), respectively, in patients treated with other immunosuppressive regimens. Renal survival (100, 80, and 72% at 5 years) and the number of patients achieving clinical remission (86, 50, and 25%) were significantly higher in patients treated with corticosteroids plus mycophenolate mofetil as compared with patients treated with other immunosuppressive regimens and untreated patients, respectively. Thus, immunosuppressive treatments, particularly corticosteroids plus mycophenolate mofetil, can be beneficial in C3 glomerulonephritis.

  14. Mycophenolate mofetil therapy for severe immune thrombocytopenia.

    PubMed

    Taylor, Alice; Neave, Lucy; Solanki, Shalini; Westwood, John Paul; Terrinonive, Ilaria; McGuckin, Siobhan; Kothari, Jaimal; Cooper, Nichola; Stasi, Roberto; Scully, Marie

    2015-11-01

    Severe immune thrombocytopenia purpura (ITP) presents a clinical challenge. Second-line treatment options are variable without a precise protocol. We present 46 severe ITP patients treated with mycophenolate mofetil (MMF), retrospectively identified from three London teaching hospitals. Data was collected on patient demographics, co-morbidities and previous treatment strategies. Our key interest was whether there was a sustained response in platelet count to MMF. Patients included 27 males and 19 females whose ages ranged from 19 to 93 years old (median 52·5 years). Twenty-nine had primary ITP and 17 had secondary ITP, a third of whom had viral-associated disease. The standard dose of MMF was 1 g/day. Twenty-four patients (52%) responded with 15 (33%) achieving a complete response. No active viral-associated ITP patients demonstrated a response to MMF, although numbers were small (n = 4). We were not able to demonstrate a difference between responders and non-responders based on gender, age, previous therapies or time since diagnosis of ITP. Three of four previously splenectomized patients responded, two achieving complete response. We conclude that MMF is a useful steroid-sparing immunosuppressant to be considered in the second-line or later treatment of ITP.

  15. Ulcerative cutaneous polyarteritis nodosa treated with mycophenolate mofetil and pentoxifylline.

    PubMed

    Kluger, Nicolas; Guillot, Bernard; Bessis, Didier

    2011-06-01

    Cutaneous polyarteritis nodosa (CPAN) is a self-limited cutaneous vasculitis characterized by painful nodules, affecting mostly the lower limbs, and livedo reticularis. Despite its benign course, CPAN may display a chronic relapsing evolution with repeated exacerbations. Ulcerative CPAN has a more prolonged evolution and is associated with peripheral neuropathy. We report on a patient with a 20-year history of ulcerative and painful CPAN, refractory to multiple immunosuppressive treatments, treated successfully by mycophenolate mofetil and pentoxifylline.

  16. EARLY TERMINATION OF A TRIAL OF MYCOPHENOLATE MOFETIL FOR TREATMENT OF INTERSTITIAL CYSTITIS/PAINFUL BLADDER SYNDROME: LESSONS LEARNED

    PubMed Central

    Yang, Claire C.; Burks, David A.; Propert, Kathleen J.; Mayer, Robert D.; Peters, Kenneth M.; Nickel, J. Curtis; Payne, Christopher K.; FitzGerald, Mary P.; Hanno, Philip M.; Chai, Toby C.; Kreder, Karl J.; Lukacz, Emily S.; Foster, Harris E.; Cen, Liyi; Landis, J. Richard; Kusek, John W.; Nyberg, Leroy M.

    2011-01-01

    Purpose To evaluate the efficacy and tolerability of mycophenolate mofetil (MMF) in patients with treatment refractory interstitial cystitis/painful bladder syndrome (IC/PBS). Materials and Methods Two hundred and ten patients with IC/PBS were to be randomized into a multicenter, placebo-controlled trial using a 2:1 randomization. Participants who had failed at least three IC/PBS-specific treatments and had at least moderately severe symptoms were enrolled in a 12-week treatment study. The primary study endpoint was the Global Response Assessment (GRA). Secondary endpoints included general and disease-specific symptom questionnaires and voiding diaries. Results Only 58 subjects were randomized before a black box warning regarding MMF safety was issued by the manufacturer in October 2007. The trial was halted, and an interim analysis was performed and presented to an independent Data and Safety Monitoring Board. Of the subjects randomized at the time of study cessation, 6/39 (15%) were considered responders for MMF, compared to 3/19 (16%) of controls (p=0.67). Secondary outcome measures reflected more improvement among controls. Conclusion In a randomized placebo-controlled trial that was prematurely halted, MMF demonstrated efficacy similar to placebo in treating symptoms of refractory IC/PBS. The results of this limited study cannot be used to confirm or refute the hypothesis that immunosuppressive therapy may be beneficial to at least a subgroup of IC\\PBS patients. Despite study termination, there are lessons that can be gleaned to inform future investigations. PMID:21238993

  17. Mycophenolate mofetil attenuates pulmonary arterial hypertension in rats

    SciTech Connect

    Suzuki, Chihiro; Takahashi, Masafumi . E-mail: masafumi@sch.md.shinshu-u.ac.jp; Morimoto, Hajime; Izawa, Atsushi; Ise, Hirohiko; Hongo, Minoru; Hoshikawa, Yasushi; Ito, Takayuki; Miyashita, Hiroshi; Kobayashi, Eiji; Shimada, Kazuyuki; Ikeda, Uichi

    2006-10-20

    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.

  18. Insights on chronic-relapsing opsoclonus-myoclonus from a pilot study of mycophenolate mofetil.

    PubMed

    Pranzatelli, Michael R; Tate, Elizabeth D; Travelstead, Anna L; Baumgardner, Christine A; Gowda, Narayana V; Halthore, Sri N; Kerstan, Peter; Kossak, Brian D; Mitchell, Wendy G; Taub, Jeffrey W

    2009-03-01

    Opsoclonus-myoclonus syndrome is characterized by abnormal lymphocyte trafficking into brain. The authors hypothesized that mycophenolate mofetil, a lymphocyte proliferation inhibitor, might be therapeutic. The cerebrospinal fluid and blood immunophenotypes of 15 children with predominantly chronic-relapsing opsoclonus-myoclonus syndrome were compared before and after treatment by flow cytometry. Mycophenolate mofetil reduced the cerebrospinal fluid expansion of HLA-DR+ activated T cells (-40%); the frequency of other T-cell or natural killer cell subsets remained unchanged, but cerebrospinal fluid B cells increased significantly. Adrenocorticotropic hormone dose was lowered by 64% over an average of 1.5 years, yet 73% eventually relapsed despite therapeutic drug levels. Prior treatment with rituximab prevented relapse-associated increase in cerebrospinal fluid B cells, without hindering mycophenolate mofetil-induced reduction in T-cell activation. These data demonstrate resistant immunologic problems in chronic-relapsing opsoclonus-myoclonus syndrome. Mycophenolate mofetil did not prevent relapse. The novel effect of mycophenolate mofetil on chronically activated T cells may contribute to its efficacy in T-cell mediated neurological disorders.

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

    PubMed

    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.

  20. Mycophenolate Mofetil (MMF) Efficacy in Glomerulonephritis (GN), a Retrospective Analysis.

    PubMed

    Huraib, Sameer O; Qureshi, Junaid I; Quadri, Khaja Hm; Al Flaiw, Ahmed; Al Ghamdi, Ghormullah; Jumani, Abdulqadir; Al Hejaili, Fayez; Raza, Hammad; Al Johani, Abdulaziz; Al-Katheri, Abdulmalik; Al-Khader, Abdullah A

    2005-01-01

    Mycophenolate Mofetil MMF has been widely used in post-transplant immunosuppression. Its role is emerging in GN. MMF demonstrated promising results compared with cyclosphosphamide in stage IV lupus nephritis, in a recently published trial. It has been found to have a wide safety profile, with mostly gastroinetestinal side effects, which can be avoided through titration. Its action is through inhibition of the enzyme IMDPH (ionosine monophosphate dehydrogenase), leading to purine antagonism and inhibition of lymphocytes. We were aiming to demonstrate the efficacy of MMF in our GN population. In this study, we reviewed 17 patients who received MMF (dose - 1 gm po bid) for the past year. They were only included if it was given for the management of resistant primary glomerulonephritis. Complete remission has been defined as proteinuria of less than 0.5 g/day and partial remission as a reduction of proteinuria 50% of starting MMF therapy; all 17 MMF therapy patients uniformly achieved good BP ((29%) achieved complete remission and this group consisted of 1 membranous GN, 2 lupus GN (type IV and membranous), one FSGS and one with MPGN. Four of 17 (23%) were non-responders to therapy. This group articles.aspx? id=41 to side effects. We conclude that the MMF appears to be an effective alternate treatment modality in resistant membranous GN, lupus nephritis (type IV and V) and possibly MPGN, and to a lesser extent in resistant FSGS. Further prospective data may demonstrate the efficacy of MMF in GN.

  1. Update on the Teratogenicity of Maternal Mycophenolate Mofetil

    PubMed Central

    Coscia, Lisa A.; Armenti, Dawn P.; King, Ryan W.; Sifontis, Nicole M.; Constantinescu, Serban; Moritz, Michael J.

    2015-01-01

    Mycophenolic acid (MPA) products, namely mycophenolate mofetil and mycophenolate sodium, are immunosuppressive medications used to prevent rejection in solid organ transplant recipients and to treat various autoimmune disorders. Mycophenolate therapy is considered to be teratogenic based on observational studies of pregnancies exposed to MPA, which demonstrated an increased incidence of miscarriages in pregnancies exposed to MPA during their first trimester and a pattern of birth defects in the offspring of some pregnancies exposed to MPA. Herein, we have detailed case and series reports in a comprehensive literature review summarizing what is known to date regarding fetal exposure to MPA. Based on evidence from the literature, results of postmarketing surveillance, and information from registries such as the National Transplantation Pregnancy Registry in the United States, it is advised that pregnancy be avoided by women taking MPA. Preconception planning offers the opportunity to explore the alternatives to protect the mother, her transplanted organ, and minimize fetal risk. How to proceed in cases of unplanned pregnancies exposed to MPA in transplant recipients is a complex issue. Research involving large epidemiological studies is expected to be sparse as women heed the warnings about becoming pregnant on MPA. Published recommendations for managing MPA in women of childbearing potential include discontinuing the medication prior to conception, switching the MPA to another medication, or discontinuing the MPA when the pregnancy is discovered. PMID:27617117

  2. Omeprazole impairs the absorption of mycophenolate mofetil but not of enteric-coated mycophenolate sodium in healthy volunteers.

    PubMed

    Kees, M G; Steinke, T; Moritz, S; Rupprecht, K; Paulus, E M; Kees, F; Bucher, M; Faerber, L

    2012-08-01

    In 2 crossover studies, 12 healthy volunteers (6 male/6 female) received a single oral dose of mycophenolate mofetil (MMF) 1000 mg or an equimolar dose of enteric-coated mycophenolate sodium (EC-MPS) 720 mg fasting with and without coadministered omeprazole 20 mg bid. The plasma concentrations of mycophenolic acid (MPA) and of the inactive metabolite mycophenolic acid glucuronide (MPA-G) were measured by high-performance liquid chromatography (HPLC). In addition, dissolution of MMF 500 mg or EC-MPS 360 mg tablets was determined using an USP paddle apparatus in aqueous buffer of pH 1 to 7. The bioavailability of MPA following administration of MMF or EC-MPS was similar except for the time to peak concentration, which was longer in the EC-MPS group. Concomitant treatment with omeprazole lowered significantly C(max) and AUC(12h) of MPA following administration of MMF. The pharmacokinetics of EC-MPS was not affected. Dissolution of MMF in aqueous buffer decreased dramatically at pH above 4.5. The EC-MPS tablet was stable up to pH 5. Above, EC-MPS was quantitatively disintegrated and MPS quantitatively dissolved. There is strong evidence that impaired absorption of MMF with concomitant proton pump inhibitors is due to incomplete dissolution of MMF in the stomach at elevated pH.

  3. Oral ulcers produced by mycophenolate mofetil in two liver transplant patients.

    PubMed

    Naranjo, J; Poniachik, J; Cisco, D; Contreras, J; Oksenberg, D; Valera, J M; Díaz, J C; Rojas, J; Cardemil, G; Mena, S; Castillo, J; Rencoret, G; Godoy, J; Escobar, J; Rodríguez, J; Leyton, P; Fica, A; Toledo, C

    2007-04-01

    Oral ulcers are a frequent problem in transplant medicine. It is important to consider infectious etiologies, exacerbated by the immunosuppressive treatment, but other etiologies are also possible, like adverse drug reactions. Mycophenolate mofetil (MMF) is an immunosuppressive medication that has been used in combination with calcineurin inhibitors and steroids. Reports of renal transplant patients with oral ulcers related to MMF have appeared lately and herein we have described 2 cases in liver transplant patients. Their oral ulcers resolved quickly after suspension of the medication. Our 2 cases in liver transplant patients represented a unique setting for this type of complication.

  4. Determination of mycophenolic acid and mycophenolate mofetil by high-performance liquid chromatography using postcolumn derivatization.

    PubMed

    Renner, U D; Thiede, C; Bornhäuser, M; Ehninger, G; Thiede, H M

    2001-01-01

    An efficient method to lower the optical detection limit is described using the displacement of an absorption and emission band of an analyte after a polarity change in different solvents. This solvatochromic effect was used in a RP-HPLC assay for the fluorescence detection of mycophenolic acid (6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-5-phthalanyl)-4-methyl-4-hexenoic acid, MPA) and the prodrug mycophenolate mofetil (MMF), the N-(2-hydroxyethyl)morpholino ester of MPA. The rational to use fluorescence detection is based on the behavior of MMF and MPA, which fluoresce in a basic medium (pH >9.5). Following a simple protein precipitation, the analytes were separated in an isocratic RP-HPLC system. The postcolumn generation of the phenolate anions of MPA and MMF was achieved by addition of an aqueous sodium hydroxide solution regulated by a newly developed continuous-flow liquid control system. MPAG, not directly accessible for fluorescence detection, was analyzed after enzymatic deglucuronidation to MPA. Compared to published quantification limits for MPA and MMF by UV detection, this method is more than 100-fold more sensitive, with a lower limit of quantification of 45 fmol for both MPA and MMF.

  5. Population pharmacokinetics and dose optimization of mycophenolic acid in HCT recipients receiving oral mycophenolate mofetil.

    PubMed

    Li, H; Mager, D E; Sandmaier, B M; Maloney, D G; Bemer, M J; McCune, J S

    2013-04-01

    We sought to create a population pharmacokinetic model for total mycophenolic acid (MPA), to study the effects of different covariates on MPA pharmacokinetics, to create a limited sampling schedule (LSS) to characterize MPA exposure (i.e., area under the curve or AUC) with maximum a posteriori Bayesian estimation, and to simulate an optimized dosing scheme for allogeneic hematopoietic cell transplantation (HCT) recipients. Four thousand four hundred ninety-six MPA concentration-time points from 408 HCT recipients were analyzed retrospectively using a nonlinear mixed effects modeling approach. MPA pharmacokinetics was characterized with a two-compartment model with first-order elimination and a time-lagged first-order absorption process. Concomitant cyclosporine and serum albumin were significant covariates. The median MPA clearance (CL) and volume of the central compartment were 24.2 L/hour and 36.4 L, respectively, for a 70 kg patient receiving tacrolimus with a serum albumin of 3.4 g/dL. Dosing simulations indicated that higher oral MMF doses are needed with concomitant cyclosporine, which increases MPA CL by 33.8%. The optimal LSS was immediately before and at 0.25 hours, 1.25 hours, 2 hours, and 4 hours after oral mycophenolate mofetil administration. MPA AUC in an individual HCT recipient can be accurately estimated using a five-sample LSS and maximum a posteriori Bayesian estimation.

  6. Safety of oral and intravenous mycophenolate mofetil in healthy cats.

    PubMed

    Slovak, Jennifer E; Villarino, Nicolas F

    2017-02-01

    Objectives The aim of this study was to evaluate the safety and clinical effects of intravenous (IV) and oral mycophenolate mofetil (MMF) in healthy cats. Methods A total of 24 healthy adult cats weighing >3.5 kg were either administered IV MMF (over a 2 h infusion) or oral MMF. The dosages used were as follows: 5 mg/kg IV once (n = 2), 10 mg/kg q12h IV for 1 day (n = 1), 20 mg/kg q12h IV for 1 day (n = 6) and 10 mg/kg q12h IV for 3 days (n = 5). Blood was collected from each cat at intervals of up to 12 h from the last dose for analysis purposes. Oral MMF was given at 10 mg/kg q12h for 7 days (n = 3), 15 mg/kg q12h for 7 days (n = 3) and 15 mg/kg q8h for 7 days (n = 4). Results Side effects to MMF were minimal. There was no anorexia or vomiting noted in any of the cats during or after IV medication administration. Only 4/14 cats had diarrhea from 12-48 h after IV administration. There was hyporexia in 1/10 cats given oral MMF and no vomiting noted. In 5/10 cats given oral MMF, there was diarrhea between days 2 and 7 of the study. Conclusions and relevance Cats tolerate MMF at an IV dose of 10 mg/kg q12h for 3 days and an oral dose ⩽15 mg/kg q12h for up to 7 days. There seems to be a dose-dependent incidence of gastrointestinal side effects. MMF may be a useful alternative immunosuppressant to be considered for use in some cats.

  7. Enhancement of Mycophenolate Mofetil Permeation for Topical Use by Eucalyptol and N-Methyl-2-pyrrolidone

    PubMed Central

    Songkram, Chalermkiat

    2016-01-01

    Mycophenolate mofetil (MMF) is a prodrug of mycophenolic acid (MPA) which can be metabolized by esterase. MMF has been approved by the United States Food and Drug Administration (USFDA) for treatment of psoriasis patient with skin symptoms. However, it remains unclear whether MMF is efficiently effective to treat skin symptoms developed from psoriasis. The insufficient amount of MMF penetrating through the skin results in the treatment failure due to the difficulty in MMF penetration through the stratum corneum. Skin permeation enhancers such as eucalyptol (EUL) and N-methyl-2-pyrrolidone (NMP) potentially aid in increasing skin penetration. This study aimed to investigate the effects of a concentration ratio (% w/v) between two enhancers (EUL and NMP). The results showed that EUL enhanced MMF permeation with an enhancement ratio (ER) of 3.44 while NMP was not able to promote the penetration of MMF. Interestingly, the synergistic effect of the two enhancers was observed with a suitable ratio given that the ER was 8.21. EUL and NMP are promising enhancers for the development of MMF based skin product. PMID:27069715

  8. Autoimmune myelofibrosis with pancytopenia as a presenting manifestation of systemic lupus erythematosus responsive to mycophenolate mofetil.

    PubMed

    Ungprasert, P; Chowdhary, V R; Davis, M D; Makol, A

    2016-04-01

    Hematological abnormalities, such as anemia, leucopenia, and thrombocytopenia, secondary to peripheral destruction, are common in systemic lupus erythematosus (SLE). However, cytopenias from autoimmune myelofibrosis (AIMF) are extremely uncommon in SLE, with less than 40 reported cases in the literature. We report the case of a 33-year-old female who presented with bullous skin lesions and pancytopenia as the presenting manifestation of what was ultimately diagnosed as SLE with AIMF. She responded well to glucocorticoids and mycophenolate mofetil.

  9. Mycophenolate mofetil as a steroid-sparing agent in sarcoid-associated renal disease.

    PubMed

    Zaidi, Anita A; DeVita, Maria V; Michelis, Michael F; Rosenstock, Jordan L

    2015-01-01

    Steroids are the mainstay of treatment for renal sarcoidosis. Many patients with sarcoidosis are chronically dependent on steroids and there is limited data on the use of steroid-sparing agents. This is a case of a patient that has remained in remission using mycophenolate mofetil (MMF) as a steroid-sparing agent. The patient is a 56-year-old female with a history of sarcoidosis diagnosed by lymph node biopsy who developed 3 episodes of acute kidney injury (AKI) in the setting of exacerbations of her sarcoidosis, each responding to prednisone treatment. Due to possible lifelong need for prednisone, MMF was started as a steroid-sparing treatment. She tolerated the MMF well and has now been steroidfree for 22 months. There have been only a few case reports about the use of MMF as a steroid-sparing agent in sarcoid-associated renal disease, in which patients could be successfully weaned off steroids. This is the longest reported follow-up of a patient being off steroids while on MMF. It is also notable for the patient having a relapse on the MMF which responded to an increased dose. MMF should be studied further as a potential steroid-sparing agent in the treatment of sarcoid associated renal disease.

  10. Infundibuloneurohypophysitis Associated With Sjögren Syndrome Successfully Treated With Mycophenolate Mofetil

    PubMed Central

    Louvet, Camille; Maqdasy, Salwan; Tekath, Marielle; Grobost, Vincent; Rieu, Virginie; Ruivard, Marc; Le Guenno, Guillaume

    2016-01-01

    Abstract Hypophysitis is an inflammatory disorder of the pituitary gland and corticosteroids are usually recommended as the first-line treatment. Hypophysitis related to primary Sjögren syndrome (pSS) is uncommon. We describe the unusual case of a patient with infundibuloneurohypophysitis associated with pSS successfully treated with mycophenolate mofetil (MMF). We describe a case of a 60-year-old man with a medical history of pSS presented with central diabetes insipidus and panhypopituitarism. Magnetic resonance imaging (MRI) revealed a thickening of the pituitary stalk and intense enhancement of the posterior pituitary, pituitary stalk, and hypothalamus. We diagnosed infundibuloneurohypophysitis associated with pSS. Hormonal replacement was started immediately and MMF was introduced without corticosteroids. After 9 months of treatment, MRI of the pituitary revealed a complete regression of the nodular thickening of the pituitary stalk, with normal enhancement and appearance of the pituitary. The pituitary axes had completely recovered, whereas the diabetes insipidus was partially restored. Our findings suggest that MMF is an effective alternative to corticosteroids for the treatment of lymphocytic hypophysitis associated with an autoimmune disease. Furthermore, this report could contribute to extend the spectrum of the neurological and endocrinological manifestations of pSS. PMID:27043673

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

    PubMed

    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.

  12. Self-resolution of Epstein-Barr virus-associated B-cell lymphoma in a patient with dermatomyositis following withdrawal of mycophenolate mofetil and methotrexate.

    PubMed

    Waldman, Mark A; Callen, Jeffrey P

    2004-08-01

    Self-resolving Epstein-Barr virus (EBV)-associated lymphomas have become more common with the use of immunosuppressive agents in both transplant patients and patients with connective tissue disorders. Immunosuppressive agents are often used for control of dermatomyositis, but their use has not been linked to subsequent malignancy. We present a 46-year-old woman with dermatomyositis, who developed an EBV-associated B-cell lymphoma of the brain while on oral methotrexate, mycophenolate mofetil and low-dose prednisone. The patient's lymphoma gradually resolved "spontaneously" upon discontinuation of the methotrexate and mycophenolate mofetil. The potential for EBV-associated B-cell lymphoma to self-resolve should be recognized by the clinician in order to prevent unnecessary and potentially toxic treatments including radiation therapy or multi-drug chemotherapy.

  13. Refractory optic perineuritis due to granulomatosis with polyangiitis successfully treated with methotrexate and mycophenolate mofetil combination therapy

    PubMed Central

    Kimura, Yoshitaka; Asako, Kurumi; Kikuchi, Hirotoshi; Kono, Hajime

    2017-01-01

    Optic perineuritis is an uncommon inflammatory disorder of the optic sheath that causes visual loss or eye pain. There are few case reports of optic perineuritis associated with granulomatosis with polyangiitis. Herein we report the case of a 37-year-old male with granulomatosis with polyangiitis and who presented with headache, blurred vision in the right eye, diplopia, and numbness in the right forehead. Brain magnetic resonance images (MRI) findings revealed hypertrophic pachymeningitis and refractory optic perineuritis. These were manageable only by means of weekly methotrexate and mycophenolate mofetil combination therapy but not with methotrexate, mycophenolate mofetil, intravenous cyclophosphamide, rituximab, azathioprine, or cyclosporine individually. PMID:28293459

  14. Pharmacokinetics of mycophenolic acid in kidney transplant recipients treated with a low dose (1 gram/day) of mycophenolate mofetil.

    PubMed

    Julasareekul, Wichian; Eiam-Ong, Somchai; Bejraputra, Ornanong; Seublinvong, Tada

    2003-08-01

    Pharmacokinetic studies of mycophenolic acid (MPA) were performed in 16 stable Thai kidney transplant recipients treated with 1 g/d of mycophenolate mofetil (MMF). The complete area under the blood concentration-time curve (AUC) of MPA was determined using the linear trapezoidal rule from 8 concentrations at, 0, 1, 2, 3, 4, 6, 8, and 12 h after MMF administration. The mean values of AUC(0-12) were 37.54 + 0.80 microg x h/ml. MPA concentrations at 8 h after dosing, not the trough or maximum levels, showed the best correlation with AUC(0-12) (r2 = 0.72). The equation model of abbreviated AUC of MPA, derived by multiple linear regression analysis, that had the highest correlation (r2) and lowest absolute prediction error (APE) was: AUC = 0.6 C1 + 1.9 C3 + 8.68 C8 + 4.65 (r2 = 0.92, APE = 2.05 +/- 0.32%). The best abbreviated AUC equations obtained by linear trapezoidal rule were: AUC = 4.5 C0 + C1 + 1.5 C2 + 5 C4 (r2 = 0.78, APE = 5.78 +/- 1.14%) and AUC = 5 C0 + C1 + C2 + 5 C3 (r2 = 0.76, APE = 6.21 +/- 1.46%).

  15. Down-regulation of multiple low dose streptozotocin-induced diabetes by mycophenolate mofetil

    PubMed Central

    MAKSIMOVIC-IVANIC, D; TRAJKOVIC, V; MILJKOVIC, DJ; STOJKOVIC, M MOSTARICA; STOSIC-GRUJICIC, S

    2002-01-01

    The new immunosuppressive agent mycophenolate mofetil (MMF) has been shown recently to exert a protective effects in certain animal models of autoimmunity, including diabetes in diabetes-prone bio-breeding (BB) rats. In the present study, the immunomodulatory potential of MMF was investigated in autoimmune diabetes induced by multiple low doses of streptozotocin (MLD-STZ) in genetically susceptible DA rats 20 mg STZ/kg body weight (b.w.) for 5 days] and CBA/H mice (40 mg STZ/kg b.w. for 5 days). In both species, short time treatment of animals with MMF (25 mg/kg) during the early development of the disease, as well as continuous MMF treatment, prevented the appearance of hyperglycaemia and inflammatory infiltrates in the pancreatic tissue. Moreover, clinical manifestations of diabetes were suppressed by application of the drug after the onset of clinical symptoms. Treatment with guanosine (1 mg/kg) in parallel with MMF completely reversed MMF activity in vivo, indicating that inhibition of inosine monophosphate dehydrogenase (IMPDH) was responsible for the observed suppressive effects. MMF-mediated protection from diabetes correlated with reduced ex vivo spontaneous spleen mononuclear cell (MNC) proliferation and defective adhesive cell interactions. MMF-treated animals also had lower local production of IFN-γ, as well as IL-12 and nitric oxide (NO) production by peripheral tissues (spleen and peritoneal cells), compared to that in control diabetic groups, while IL-10 level was elevated. Together, these data demonstrate that MMF interferes with autoimmune process in streptozotocin-induced diabetes at multiple levels, including lymphocyte proliferation and adhesion, as well as pro/anti-inflammatory cytokine balance. PMID:12165076

  16. Circadian variation of cytotoxicity and genotoxicity induced by an immunosuppressive agent "Mycophenolate Mofetil" in rats.

    PubMed

    Dridi, Ichrak; Grissa, Intissar; Ezzi, Lobna; Chakroun, Sana; Ben-Cherif, Wafa; Haouas, Zohra; Aouam, Karim; Ben-Attia, Mossadok; Reinberg, Alain; Boughattas, Naceur A

    2016-01-01

    Immunosuppressive drugs such as Mycophenolate Mofetil (MMF) are used to suppress the immune system activity in transplant patients and reduce the risk of organ rejection. The present study investigates whether the potential cytotoxicity and genotoxicity varied according to MMF dosing-time in Wistar Rat. A potentially toxic MMF dose (300 mg/kg) was acutely administered by the i.p. route in rats at four different circadian stages (1, 7, 13 and 19 hours after light onset, HALO). Rats were sacrificed 3 days following injection, blood and bone marrow were removed for determination of cytotoxicity and genotoxicity analysis. The genotoxic effect of this pro-drug was investigated using the comet assay and the micronucleus test. Hematological changes were also evaluated according to circadian dosing time. MMF treatment induced a significant decrease at 7 HALO in red blood cells, in the hemoglobin rate and in white blood cells. These parameters followed a circadian rhythm in controls or in treated rats with an acrophase located at the end of the light-rest phase. A significant, thrombocytopenia was observed according to MMF circadian dosing time. Furthermore, abnormally shaped red cells, sometimes containing micronuclei, poikilocytotic in red cells and hypersegmented neutrophil nuclei were observed with MMF treatment. The micronucleus test revealed damage to chromosomes in rat bone marrow; the comet assay showed significant DNA damage. This damage varied according to circadian MMF dosing time. The injection of MMF in the middle of the dark-activity phase produced a very mild hematological toxicity and low genotoxicity. Conversely, it induced maximum hematological toxicity and genotoxicity when the administration occurred in the middle of the light-rest phase, which is physiologically analogous to the end of the activity of the diurnal phase in human patients.

  17. Improved gastrointestinal symptoms and quality of life after conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in renal transplant patients receiving tacrolimus.

    PubMed

    Hwang, Hyeon Seok; Hyoung, Bok Jin; Kim, Sol; Oh, Ha Young; Kim, Yon Su; Kim, Jung Kyung; Kim, Yeong Hoon; Kim, Yong Lim; Kim, Chan Duck; Shin, Gyu Tae; Yang, Chul Woo

    2010-12-01

    It is reported that a conversion from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) relieves gastrointestinal (GI) symptom burden and improves health-related quality of life (HRQoL). However, it is unclear whether renal transplant recipients using tacrolimus receive the same benefit from the conversion. In this prospective, multi-center, open-label trial, patients were categorized into two groups by their GI symptom screening. Equimolar EC-MPS (n=175) was prescribed for patients with GI burdens; those with no complaints remained on MMF (n=83). Gastrointestinal Symptom Rating Scale (GSRS) and Gastrointestinal Quality of Life Index (GIQLI) were evaluated at baseline and after one month. Patients and physicians completed Overall Treatment Effect (OTE) at one month. EC-MPS-converted patients had worse GSRS and GIQLI scores at baseline than MMF-continued patients (all P<0.001). Significant improvements in GSRS and GIQLI scores were observed for EC-MPS-converted patients at one month, but MMF-continued patients showed worsened GSRS scores (all P<0.05). OTE scale indicated that EC-MPS patients improved in overall GI symptoms and HRQoL more than MMF patients did (P<0.001). In tacrolimus-treated renal transplant recipients with GI burdens, a conversion from MMF to EC-MPS improves GI-related symptoms and HRQoL.

  18. Spectroscopy and Molecular Modeling Study on the Interaction Between Mycophenolate Mofetil and Pepsin.

    PubMed

    Ma, Xiaoli; Guo, Liuqi; Wang, Qing; He, Jiawei; Li, Hui

    2016-03-01

    Mycophenolate mofetil (MMF) is an immunosuppressant used in clinical practice to limit the rejection of transplanted organs. MMF is absorbed and metabolized by the gastrointestinal tract and converted to mycophenolic acid by esterases in the plasma, liver, and kidney. Mycophenolic acid is the resulting active metabolite. The interaction of MMF with pepsin may affect the transfer and distribution of MMF. Given this effect, the present study investigated the interaction behavior between pepsin with MMF using docking simulation and spectroscopy method at different temperatures. The results of spectroscopy revealed that MMF has strong ability to quench the fluorescence of pepsin. The results also show that the acting force for binding was composed of hydrophobic forces. The three-dimensional fluorescence spectra and synchronous spectroscopy employed to determine the conformation showed that the binding of MMF with pepsin could induce MMF conformation and microenvironment changes. Furthermore, the molecular interaction distance and energy-transfer efficiency between pepsin and MMF were determined based on the Förster non-radiative energy-transfer mechanism. Docking simulation showed that MMF entered the hydrophobic cavity of pepsin, and a hydrogen bond was formed between the oxygen atoms of the carbanyl group of MMF and hydrogen atoms of tyrosine 189 of pepsin.

  19. Population Pharmacokinetics and Dose Optimization of Mycophenolic Acid in HCT Recipients Receiving Oral Mycophenolate Mofetil

    PubMed Central

    Li, H; Mager, D E; Sandmaier, B M; Maloney, D G; Bemer, M J; McCune, J S

    2012-01-01

    We sought to create a population pharmacokinetic model for total mycophenolic acid (MPA), to study the effects of different covariates on MPA pharmacokinetics, to create a limited sampling schedule (LSS) to characterize MPA exposure (i.e., area under the curve or AUC) with maximum a posteriori Bayesian estimation, and to simulate an optimized dosing scheme for allogeneic hematopoietic cell transplantation (HCT) recipients. 4,496 MPA concentration-time points from 408 HCT recipients were analyzed retrospectively using a nonlinear mixed effects modeling approach. MPA pharmacokinetics was characterized with a two-compartment model with first-order elimination and a time-lagged first-order absorption process. Concomitant cyclosporine and serum albumin were significant covariates. The median MPA clearance and volume of the central compartment were 24.2 L/hr and 36.4 L, respectively, for a 70 kg patient receiving tacrolimus with a serum albumin of 3.4 g/dL. Dosing simulations indicated that higher oral MMF doses are needed with concomitant cyclosporine, which increases MPA clearance by 33.8%. The optimal LSS was immediately before and at 0.25, 1.25, 2, and 4hr after oral MMF administration. MPA AUC in an individual HCT recipient can be accurately estimated using a five-sample LSS and maximum a posteriori Bayesian estimation. PMID:23382105

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

    PubMed

    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.

  1. Mycophenolate mofetil (MMF): firing at the atherosclerotic plaque from different angles?

    PubMed

    van Leuven, Sander I; Kastelein, John J P; Allison, Anthony C; Hayden, Michael R; Stroes, Erik S G

    2006-02-01

    Atherosclerosis is characterized by a persistent, low-grade inflammatory state in which immune cell activation is inseparably linked to plaque formation and destabilization. The T-lymphocyte in particular has emerged as a pivotal player throughout the course of atherogenesis. As a consequence, the concept that immune modulation is a suitable target for cardiovascular prevention is currently an important focus of research. Mycophenolate mofetil (MMF) has emerged as a non-competitive inhibitor of inosine monophosphate dehydrogenase (IMPDH) that exerts cytostatic effects, particularly on proliferating T-lymphocytes. In addition, MMF has other immune-modulating effects, such as downregulation of the expression of adhesion molecules and attenuation of monocyte and macrophage responses. Given the added benefit that MMF is well tolerated, this immunosuppressive agent constitutes an attractive candidate for the modulation of inflammatory activation in atherogenesis. The present review provides an overview of the potential anti-atherogenic properties of MMF.

  2. Mycophenolate mofetil toxicity mimicking acute cellular rejection in a small intestinal transplant

    PubMed Central

    Apostolov, Ross; Asadi, Khashayar; Lokan, Julie; Kam, Ning; Testro, Adam

    2017-01-01

    Mycophenolate mofetil (MMF) is an important medication used for maintenance immunosuppression in solid organ transplants. A common gastrointestinal (GI) side effect of MMF is enterocolitis, which has been associated with multiple histological features. There is little data in the literature describing the histological effects of MMF in small intestinal transplant (SIT) recipients. We present a case of MMF toxicity in a SIT recipient, with histological changes in the donor ileum mimicking persistent acute cellular rejection (ACR). Concurrent biopsies of the patient’s native colon showed similar changes to those from the donor small bowel, suggesting a non-graft specific process, raising suspicion for MMF toxicity. The MMF was discontinued and complete resolution of these changes occurred over three weeks. MMF toxicity should therefore be considered as a differential diagnosis for ACR and graft-versus-host disease in SITs. PMID:28280702

  3. Liquid chromatography tandem mass spectrometry method for the quantitation of mycophenolate mofetil in human plasma: Application to a bioequivalence study and metabolite identification.

    PubMed

    Partani, Pankaj; Verma, Saurabh Manaswita; Monif, Tausif

    2015-10-01

    We established a sensitive, selective, and rapid analytical method for the quantitation and pharmacokinetic investigation of mycophenolate mofetil in human plasma. To our knowledge, this is the first method that characterizes presence of mycophenolate mofetil glucuronide in clinical samples through tandem mass spectrometry detection and resolves mycophenolate mofetil from its glucuronide metabolite. Liquid chromatography coupled to tandem mass spectrometry detection in positive ion mode was selected to provide optimal selectivity and sensitivity. Due to the ionizable characteristics of the mycophenolate mofetil, a mixed-mode cation-exchange disposable extraction cartridge was prudently chosen. The chromatographic separation was achieved on Luna(®) C18(2) (100×4.60 mm) column using mobile phase consisting of a mixture of 1±0.05 mM ammonium formate in water, titrated to pH 3.1±0.1 with formic acid, and methanol (20:80, v/v), at a flow rate of 0.7 mL/min. The detection was led at m/z ratios of 434.4→ 114.2 and 438.4→ 118.3, for mycophenolate mofetil and mycophenolate mofetil-D4, respectively. The developed method was linear between 40.2-4986.0 pg/mL. All validation parameters were within the defined limits. The validated method was then successfully applied for the evaluation of bioequivalence parameters of mycophenolate mofetil after an oral administration of 500 mg mycophenolate mofetil tablet to healthy male Indian volunteers.

  4. Oral mycophenolate mofetil prevents in-stent intimal hyperplasia without edge effect.

    PubMed

    Ilkay, Erdogan; Tirikli, Latif; Ozercan, Ibrahim; Yavuzkir, Mustafa; Karaca, Ilgin; Rahman, Ali; Arslan, Nadi

    2006-01-01

    Neointimal hyperplasia is in the forefront in in-stent restenosis. Prevention of in-stent restenosis is possible by reducing and inhibiting the hyperplasia of smooth muscle cells. The authors planned this study to test the hypothesis that when administered orally, mycophenolate mofetil (MMF) could inhibit in-stent neointimal hyperplasia. The study included 14 New Zealand rabbits. The rabbits were allocated to 2 different groups: Group 1 included 7 rabbits that were given MMF, 40 mg/kg/day by oral route. Group 2 included 7 rabbits that were not given MMF after the stenting. Sampling materials were taken before and after stenting by incising the artery so as to cover a 5-mm area. The samples taken from the edge of the stent in Group 1 showed focal neointimal cell proliferation, but it was less than that from the control group. Neointimal thickness was 0.048 +/-0.009 mm and neointimal area was 0.0925 +/-0.019 mm(2). Apparent neointimal cell proliferation and thickening of the intimal layer were observed in Group 2. Neointimal thickness at the stent edge was 0.147 +/-0.051 mm and the neointimal area was 0.154 +/-0.023 mm(2). The differences between groups in terms of neointimal thickness and neointimal area were statistically significant (p=0.001 for thickness and p=0.001 for area). In-stent artery samples of Group 1 showed that some subjects had no neointimal cell proliferation, while others had very limited focal intimal thickening. Neointimal thickening was 0.071 +/-0.003 mm and neointimal area was 0.073 +/-0.003 mm(2). In Group 2 apparent, and mostly focal, neointimal cell proliferation and formation of intimal layer were observed in the stent. Neointimal thickening was 0.154 +/-0.069 mm and neointimal area was 0.279 +/-0.059 mm(2). The comparison between groups showed significant differences (p=0.011 for thickness and p=0.001 for area). It was established in the third month that endothelialization was completed in both groups. Oral MMF decreased in-stent intimal

  5. The use of mycophenolate mofetil suspension in pediatric renal allograft recipients.

    PubMed

    Bunchman, T; Navarro, M; Broyer, M; Sherbotie, J; Chavers, B; Tönshoff, B; Birk, P; Lerner, G; Lirenman, D; Greenbaum, L; Walker, R; Zimmerhackl, L B; Blowey, D; Clark, G; Ettenger, R; Arterburn, S; Klamerus, K; Fong, A; Tang, H; Thomas, S; Ramos, E

    2001-12-01

    Mycophenolate mofetil (MMF) is widely used to prevent acute rejection in adults after renal, cardiac, and liver transplantation. This study investigated the safety, tolerability, and pharmacokinetics of MMF suspension in pediatric renal allograft recipients. One hundred renal allograft recipients were enrolled into three age groups (33 patients, 3 months to <6 years; 34 patients, 6 to <12 years; 33 patients, 12 to 18 years). Patients received MMF 600 mg/m2 b.i.d. concomitantly with cyclosporine and corticosteroids with or without antilymphocyte antibody induction. One year after transplantation, patient and graft survival (including death) were 98% and 93%, respectively. Twenty-five patients (25%) experienced a biopsy-proven (Banff grade borderline or higher) or presumptive acute rejection within the first 6 months post-transplantation. Analysis of pharmacokinetic parameters for mycophenolic acid (MPA) and mycophenolic acid glucuronide showed no clinically significant differences among the age groups. The dosing regimen of MMF 600 mg/m2 b.i.d. achieved the targeted early post-transplantation MPA 12-h area under concentration-time curve (AUC0-12) of 27.2 microg h per ml. Adverse events had similar frequencies among the age groups (with the exception of diarrhea, leukopenia, sepsis, and anemia, which were more frequent in the <6 years age group) and led to withdrawal of MMF in about 10% of patients. Administration of MMF 600 mg/m2 b.i.d. is effective in prevention of acute rejection, provides predictable pharmacokinetics, and is associated with an acceptable safety profile in pediatric renal transplant recipients.

  6. Influence of cyclosporine and everolimus on the main mycophenolate mofetil pharmacokinetic parameters

    PubMed Central

    Noreikaitė, Aurelija; Saint-Marcoux, Franck; Marquet, Pierre; Kaduševičius, Edmundas; Stankevičius, Edgaras

    2017-01-01

    Abstract The objective of the present study was to assess the effect of cyclosporine (CsA) on the pharmacokinetic parameters of mycophenolic acid (MPA), an active mycophenolate mofetil (MMF) metabolite, and to compare with the effect of everolimus (EVR). Anonymized medical records of 404 kidney recipients were reviewed. The main MPA pharmacokinetic parameters (AUC(0–12) and Cmax) were evaluated. The patients treated with a higher mean dose of CsA displayed higher MPA AUC(0–12) exposure in the low-dose MMF group (1000 mg/day) (40.50 ± 10.97 vs 28.08 ± 11.03 h mg/L; rs = 0.497, P < 0.05), medium-dose MMF group (2000 mg/day) (43.00 ± 6.27 vs 28.85 ± 11.08 h mg/L; rs = 0.437, P < 0.01), and high-dose MMF group (3000 mg/day) (56.75 ± 16.78 vs 36.20 ± 3.70 h mg/L; rs = 0.608, P < 0.05). A positive correlation was also observed between the mean CsA dose and the MPA Cmax in the low-dose MMF group (Cmax 22.83 ± 10.82 vs 12.08 ± 5.59 mg/L; rs = 0.507, P < 0.05) and in the medium-dose MMF group (22.77 ± 8.86 vs 13.00 ± 6.82 mg/L; rs = 0.414, P < 0.01). The comparative analysis between 2 treatment arms (MMF + CsA and MMF + EVR) showed that MPA AUC(0–12) exposure was by 43% higher in the patients treated with a medium dose of MMF and EVR than in the patients treated with a medium dose of MMF and CsA. The data of the present study suggest a possible CsA versus EVR influence on MMF pharmacokinetics. Study results show that CsA has an impact on the main MPA pharmacokinetic parameters (AUC(0–12) and Cmax) in a CsA dose-related manner, while EVR mildly influence or does not affect MPA pharmacokinetic parameters. Low-dose CsA (lower than 180 mg/day) reduces MPA AUC(0–12) exposure under the therapeutic window and may lead to ineffective therapy, while a high-dose CsA (>240 mg/day) is related to greater than 10 mg/L MPA Cmax and increases the

  7. Influence of cyclosporine and everolimus on the main mycophenolate mofetil pharmacokinetic parameters: Cross-sectional study.

    PubMed

    Noreikaitė, Aurelija; Saint-Marcoux, Franck; Marquet, Pierre; Kaduševičius, Edmundas; Stankevičius, Edgaras

    2017-03-01

    The objective of the present study was to assess the effect of cyclosporine (CsA) on the pharmacokinetic parameters of mycophenolic acid (MPA), an active mycophenolate mofetil (MMF) metabolite, and to compare with the effect of everolimus (EVR).Anonymized medical records of 404 kidney recipients were reviewed. The main MPA pharmacokinetic parameters (AUC(0-12) and Cmax) were evaluated.The patients treated with a higher mean dose of CsA displayed higher MPA AUC(0-12) exposure in the low-dose MMF group (1000 mg/day) (40.50 ± 10.97 vs 28.08 ± 11.03 h mg/L; rs = 0.497, P < 0.05), medium-dose MMF group (2000 mg/day) (43.00 ± 6.27 vs 28.85 ± 11.08 h mg/L; rs = 0.437, P < 0.01), and high-dose MMF group (3000 mg/day) (56.75 ± 16.78 vs 36.20 ± 3.70 h mg/L; rs = 0.608, P < 0.05).A positive correlation was also observed between the mean CsA dose and the MPA Cmax in the low-dose MMF group (Cmax 22.83 ± 10.82 vs 12.08 ± 5.59 mg/L; rs = 0.507, P < 0.05) and in the medium-dose MMF group (22.77 ± 8.86 vs 13.00 ± 6.82 mg/L; rs = 0.414, P < 0.01).The comparative analysis between 2 treatment arms (MMF + CsA and MMF + EVR) showed that MPA AUC(0-12) exposure was by 43% higher in the patients treated with a medium dose of MMF and EVR than in the patients treated with a medium dose of MMF and CsA.The data of the present study suggest a possible CsA versus EVR influence on MMF pharmacokinetics. Study results show that CsA has an impact on the main MPA pharmacokinetic parameters (AUC(0-12) and Cmax) in a CsA dose-related manner, while EVR mildly influence or does not affect MPA pharmacokinetic parameters. Low-dose CsA (lower than 180 mg/day) reduces MPA AUC(0-12) exposure under the therapeutic window and may lead to ineffective therapy, while a high-dose CsA (>240 mg/day) is related to greater than 10 mg/L MPA Cmax and increases the likelihood of adverse events.

  8. Evaluation of limited sampling strategies for mycophenolic acid after mycophenolate mofetil intake in adult kidney transplant recipients.

    PubMed

    Barraclough, Katherine A; Isbel, Nicole M; Franklin, Michael E; Lee, Katie J; Taylor, Paul J; Campbell, Scott B; Petchey, William G; Staatz, Christine E

    2010-12-01

    Multiple limited sampling strategies (LSSs) have been proposed for estimation of mycophenolic acid (MPA) area under the concentration-time curve from 0 to 12 hours postdose (AUC 0-12) after mycophenolate mofetil intake. The aim of this study was to provide summary information on all published LSSs for MPA and to evaluate their predictive performance in an independent population of kidney transplant recipients. Seventy-eight LSSs for MPA were identified. Sixty-nine full AUC profiles were collected from 45 subjects (25 cotreated with cyclosporine and 20 with tacrolimus). Predicted MPA AUC 0-12, calculated by applying the relevant concentration measurements within the LSS equations, was compared with full AUC calculated by using all concentration measurements in the linear trapezoidal rule. Four error indices (median prediction error, median percentage prediction error [MPPE], root median squared prediction error, and median absolute percentage prediction error [MAPE]) were used to evaluate bias and imprecision. Twelve of the 25 LSSs for cyclosporine-cotreated recipients and one of the 53 LSSs for tacrolimus-cotreated recipients displayed acceptable (less than 15%) bias and imprecision. In the cyclosporine group, two equations demonstrated the highest predictive power, one that used four time points in the first 6 hours postdose (r2 = 0.84, MPPE 1.6%, MAPE 7.8%) and one that used four time points in the first 4 hours postdose (r2 = 0.76, MPPE -0.8%, MAPE 10.2%). In the tacrolimus group, an equation that used two time points in the first 4 hours postdose was superior (r2 = 0.80, MPPE -3.0%, MAPE 13.6%). Application of the LSSs most appropriate for cyclosporine-cotreated patients to the tacrolimus-cotreated group resulted in clinically unacceptable bias and imprecision and vice versa. High variability in performance of LSSs highlights the importance of validating any LSS before applying it to an alternative population. Attention to comedication use is of particular

  9. A case of non-regenerative immune-mediated anemia treated by combination therapy of human immune globulin and mycophenolate mofetil in a dog.

    PubMed

    Yuki, M

    2011-01-01

    A 12-year-old female Shih Tzu dog was referred with diarrhea. Hematological examination indicated severe non-regenerative anemia. Bone marrow aspiration smears and core biopsy specimens revealed normal bone marrow. Based on those results, non-regenerative immune-mediated anemia was diagnosed. The dog was initially treated using prednisolone and cyclosporine. However, this treatment regimen did not prove effective. Nevertheless, the patient achieved a good hematological response after the administration of a combination therapy of human immune globulin and mycophenolate mofetil. Such a combination therapy may prove effective against non-regenerative immune-mediated anemia.

  10. Involvement of carboxylesterase 1 and 2 in the hydrolysis of mycophenolate mofetil.

    PubMed

    Fujiyama, Nobuhiro; Miura, Masatomo; Kato, Shoutaro; Sone, Tomomichi; Isobe, Masakazu; Satoh, Shigeru

    2010-12-01

    Mycophenolate mofetil (MMF) is the ester prodrug of the immunosuppressant agent mycophenolic acid (MPA) and is rapidly activated by esterases after oral administration. However, the role of isoenzymes in MMF hydrolysis remains unclear. Although human plasma, erythrocytes, and whole blood contain MMF hydrolytic activities, the mean half-lives of MMF in vitro were 15.1, 1.58, and 3.20 h, respectively. Thus, blood esterases seemed to contribute little to the rapid MMF disappearance in vivo. In vitro analyses showed that human intestinal microsomes exposed to 5 and 10 μM MMF exhibited hydrolytic activities of 2.38 and 4.62 nmol/(min · mg protein), respectively. Human liver microsomes exhibited hydrolytic activities of 14.0 and 26.1 nmol/(min · mg protein), respectively, approximately 6-fold higher than those observed for intestinal microsomes. MMF hydrolytic activities in human liver cytosols were 1.40 and 3.04 nmol/(min · mg protein), respectively. Because hepatic cytosols generally contain 5-fold more protein than microsomes, MMF hydrolysis in human liver cytosols corresponded to approximately 50% of that observed in microsomes. Fractions obtained by 9000g centrifugation of supernatants from COS-1 cells expressing human carboxylesterase (CES) 1 or 2 exhibited MMF hydrolytic activity, with CES1-containing fractions showing higher catalytic efficiency than CES2-containing fractions. The CES inhibitor bis-p-nitrophenylphosphate inhibited MMF hydrolysis in human liver microsomes and cytosols with IC(50) values of 0.51 and 0.36 μM, respectively. In conclusion, both intestinal and hepatic CESs and in particular CES1 may be involved in MMF hydrolysis and play important roles in MMF bioactivation. Hepatic CES1 activity levels may help explain the between-subject variability observed for MMF usage.

  11. Pneumocystis jirovecii pneumonia in mycophenolate mofetil-treated patients with connective tissue disease: analysis of 17 cases.

    PubMed

    Zhang, Yongfeng; Zheng, Yi

    2014-12-01

    The association of Pneumocystis jirovecii pneumonia (PJP) with connective tissue disease (CTD) and mycophenolate mofetil's (MMF) potent activity against PJP have been separately reported. Until now, there have been no papers describing the occurrence of PJP following MMF treatment in CTD patients. The objective of this study was to describe the clinical features, risk factors, outcomes of PJP in patients with CTD and investigates the effects of MMF on the occurrence of PJP in China. In this retrospective cohort study, we performed a chart review, analyzing clinical features, treatment, and outcomes of PJP in patients with CTD in a single hospital. A total of 17 cases met the inclusion criteria of having PJP and a CTD diagnosis: systemic lupus erythematosus; polymyositis; dermatomyositis; rheumatoid arthritis; Wegener's granulomatosis; and microscopic polyangiitis. Sixteen patients were treated with glucocorticoids (GCs) plus immunosuppressive drugs. Only one patient had GCs without immunosuppressive drugs. Ten subjects (62.5 %) received MMF (1-1.5 g/day), and all ten had lymphopenia. The mortality rates of MMF and non-MMF patients were 50 and 14 %, respectively. This study is the first report of PJP following MMF plus GC treatment in patients with CTD. CTD itself may be a risk factor for PJP. When CTD patients receiving MMF therapy have low lymphocyte counts and/or CD4 lymphocyte counts <250/µL, we should be care of occurrence of PJP.

  12. Physical and Chemical Stability of Mycophenolate Mofetil (MMF) Suspension Prepared at the Hospital.

    PubMed

    Fahimi, Fanak; Baniasadi, Shadi; Mortazavi, Seyed Alireza; Dehghan, Hanie; Zarghi, Afshin

    2012-01-01

    To evaluate the physical and chemical stability of a suspension of mycophenolate mofetil (MMF) prepared in the hospital from commercially available MMF capsules and tablets. Extemporaneous pharmacy was used as a feasible method in this experimental study to prepare suspension form of MMF. Suspension formulations were prepared from both tablets and capsules forms of MMF. Thereafter the stability parameters such as pH, microbial control, thermal and physical stability and particle sizes were evaluated. The amount of MMF, in the suspension was measured at various time points by HPLC. The HPLC method showed that concentration of suspensions prepared from tablets and capsules were 49 mg/mL and 50 mg/mL at time 0, respectively. The effective amount of suspensions prepared from capsules was 101% at time 0, 100% after 7 days, 98% after 14 days, and less than 70% after 28 days. According to the obtained results in this study, capsule-based suspension was stable for as long as 14 days at 5°C. This formulation appears to be clinically acceptable and provides a convenient dosage form for pediatric patients and for adults during the early postoperative period.

  13. Fructooligosaccharide raftilose reduces the mycophenolate mofetil-induced complications: Hematological and biochemical alterations.

    PubMed

    Cheraghi, Hadi; Khaki, Zohreh; Malekinejad, Hassan; Sasani, Farhang

    2015-01-01

    Mycophenolate mofetil (MMF) is a selective inhibitor of Inosine-5'-monophosphate dehydrogenase. Gastrointestinal (GI) disturbances in immature ones are reported for MMF-induced compilations, which in the case of occurrence dose reduction is required. Thus, in the present study, the fructooligosaccharide raftilose(®) (RFT) was co-administrated with MMF to estimate the protective effect of RFT against MMF-induced GI complications. Thirty six immature male Wistar rats were divided into six groups including: Control (normal saline), RFT-treated (100 mg kg(-1)), MMF-treated (20 mg kg(-1)), MMF + LRFT (50 mg kg(-1)), MMF + MRFT (100 mg kg(-1)) and MMF + HRFT (200 mg kg(-1)) groups. The hematocrit (Hct), lymphocyte/total WBC, feces water content and pH were analyzed. Moreover, the hepatic functional tests, kidney-related biomarkers, lipid and protein profiles, total antioxidant capacity (TAC), malondialdehyde (MDA) and nitric oxide (NO) contents were assessed. Co-administration of RFT stabilized the MMF-reduced body weight. The MMF significantly diminished Hct and lymph/total WBC (p < 0.05). Only MRFT enhanced the lymphocyte/total WBC. Increased water content, no changes in feces pH, increased serum ALT and AST, no alteration in urea and mild enhancement in creatinine were demonstrated in MMF-received animals. However, RFT at low dose ameliorated the feces parameters and reduced ALT. No significant changes were demonstrated for serum lipid and protein profiles in MMF- and RFT + MMF-treated groups. The RFT enhanced the serum TAC, reduced MDA and NO contents. In conclusion, our data suggested that RFT could be considered as an effective agent to subsidize the MMF-induced clinical, hematological and biochemical disorders.

  14. Fructooligosaccharide raftilose reduces the mycophenolate mofetil-induced complications: Hematological and biochemical alterations

    PubMed Central

    Cheraghi, Hadi; Khaki, Zohreh; Malekinejad, Hassan; Sasani, Farhang

    2015-01-01

    Mycophenolate mofetil (MMF) is a selective inhibitor of Inosine-5′-monophosphate dehydrogenase. Gastrointestinal (GI) disturbances in immature ones are reported for MMF-induced compilations, which in the case of occurrence dose reduction is required. Thus, in the present study, the fructooligosaccharide raftilose® (RFT) was co-administrated with MMF to estimate the protective effect of RFT against MMF-induced GI complications. Thirty six immature male Wistar rats were divided into six groups including: Control (normal saline), RFT-treated (100 mg kg-1), MMF-treated (20 mg kg-1), MMF + LRFT (50 mg kg-1), MMF + MRFT (100 mg kg-1) and MMF + HRFT (200 mg kg-1) groups. The hematocrit (Hct), lymphocyte/total WBC, feces water content and pH were analyzed. Moreover, the hepatic functional tests, kidney-related biomarkers, lipid and protein profiles, total antioxidant capacity (TAC), malondialdehyde (MDA) and nitric oxide (NO) contents were assessed. Co-administration of RFT stabilized the MMF-reduced body weight. The MMF significantly diminished Hct and lymph/total WBC (p < 0.05). Only MRFT enhanced the lymphocyte/total WBC. Increased water content, no changes in feces pH, increased serum ALT and AST, no alteration in urea and mild enhancement in creatinine were demonstrated in MMF-received animals. However, RFT at low dose ameliorated the feces parameters and reduced ALT. No significant changes were demonstrated for serum lipid and protein profiles in MMF- and RFT + MMF-treated groups. The RFT enhanced the serum TAC, reduced MDA and NO contents. In conclusion, our data suggested that RFT could be considered as an effective agent to subsidize the MMF-induced clinical, hematological and biochemical disorders. PMID:26973768

  15. Mycophenolate mofetil prevents cerebrovascular injury in stroke-prone spontaneously hypertensive rats.

    PubMed

    Dhande, Isha S; Zhu, Yaming; Braun, Michael C; Hicks, M John; Wenderfer, Scott E; Doris, Peter A

    2017-03-01

    Stroke-prone spontaneously hypertensive rats (SHR-A3) develop strokes and progressive kidney disease as a result of naturally occurring genetic variations. We recently identified genetic variants in immune signaling pathways that contribute to end-organ injury. The present study was designed to test the hypothesis that a dysregulated immune response promotes stroke susceptibility. We salt-loaded 20 wk old male SHR-A3 rats and treated them with the immunosuppressant mycophenolate mofetil (MMF, 25 mg/kg/day po) (n = 8) or vehicle (saline) (n = 9) for 8 wk. Blood pressure (BP) was measured weekly by telemetry. Compared with vehicle-treated controls, MMF-treated SHR-A3 rats had improved survival and lower neurological deficit scores (1.44 vs. 0.125; P < 0.02). Gross morphology of the brain revealed cerebral edema in 8 of 9, and microbleeds and hemorrhages in 5 of 9 vehicle-treated rats. These lesions were absent in MMF-treated rats. Brain CD68 expression, indicating macrophage/microglial activation, was upregulated in vehicle-treated rats with microbleeds and hemorrhages but was undetectable in the brains of MMF-treated rats. MMF also prevented renal injury in SHR-A3 rats, evidenced by reduced proteinuria (albumin:creatinine) from 7.52 to 1.05 mg/mg (P < 0.03) and lower tubulointerstitial injury scores (2.46 vs. 1.43; P < 0.01). Salt loading resulted in a progressive increase in BP, which was blunted in rats receiving MMF. Our findings provide evidence that abnormal immune activation predisposes to cerebrovascular and renal injury in stroke-prone SHR-A3 rats.

  16. Mycophenolate mofetil suspension in pediatric renal transplantation: three-year data from the tricontinental trial.

    PubMed

    Höcker, Britta; Weber, Lutz T; Bunchman, Timothy; Rashford, Michelle; Tönshoff, Burkhard

    2005-08-01

    Mycophenolate mofetil (MMF) is widely used to prevent acute rejection in adult solid organ transplant recipients, but data in children and adolescents are scarce. This prospective, multicenter, open-labeled, single-arm study investigated the efficacy and safety of an MMF-based immunosuppressive regimen in 100 pediatric renal transplant recipients over a 3-yr period of time. Three age groups were formed (<6 yr, n = 33; 6 to <12 yr, n = 34; 12-18 yr, n = 33). Basic immunosuppression consisted of MMF (600 mg/m(2) b.i.d), cyclosporin A microemulsion and corticosteroids. Seventy-three percent of patients were given anti-lymphocyte antibody induction therapy, of whom 74% received anti-thymocyte globulin. Patient and graft survival 3 yr after transplantation amounted to 98 and 95%, respectively. Twenty-five percent of all patients suffered a biopsy-proven acute rejection episode in the first 6 month post-transplant. Children undergoing induction therapy exhibited a numerically lower rejection rate (21 vs. 37%, p = 0.11). Three years after transplantation, the acute rejection rate added up to 30% (26% with induction therapy vs. 41% without induction therapy, p = 0.21). The number of patients with acute rejection was lowest in the youngest age group (18%), in comparison with 39% in the 6 to <12 yr and 33% in the 12-18 yr age group, respectively. For the entire patient population, the rate of patients who withdrew prematurely because of adverse events was low (12%). The present study shows that MMF therapy in pediatric renal transplant recipients leads to an excellent patient and graft survival 3 yr post-transplant with an acceptable safety profile.

  17. Autoimmune lymphoproliferative syndrome: response to mycophenolate mofetil and pyrimethamine/sulfadoxine in a 5-year-old child.

    PubMed

    Arora, Sunaina; Singh, Neeraj; Chaudhary, Gurmeet Kaur; John, M Joseph

    2011-06-01

    Autoimmune Lymphoproliferative Syndrome (ALPS) is a rare inherited disorder of disrupted lymphocyte homeostasis characterized by chronic splenomegaly and lymphadenopathy of early onset, hypergammaglobulinemia (Ig G and Ig A), autoimmune phenomena, and expanded populations of TCR-α/β+, CD3+, CD4-, CD8-T cells (Fisher et al. Cell 81:935-946; 1995), called double negative T-cells [(DN) T cells]. We discuss a case of ALPS which showed good response to immunosuppressant drug Mycophenolate-Mofetil in combination with Pyrimethamine/Sulfadoxine.

  18. Tacrolimus with mycophenolate mofetil (MMF) or sirolimus vs. cyclosporine with MMF in cardiac transplant patients: 1-year report.

    PubMed

    Kobashigawa, J A; Miller, L W; Russell, S D; Ewald, G A; Zucker, M J; Goldberg, L R; Eisen, H J; Salm, K; Tolzman, D; Gao, J; Fitzsimmons, W; First, R

    2006-06-01

    The most advantageous combination of immunosuppressive agents for cardiac transplant recipients has not yet been established. Between November 2001 and June 2003, 343 de novo cardiac transplant recipients were randomized to receive steroids and either tacrolimus (TAC) + sirolimus (SRL), TAC + mycophenolate mofetil (MMF) or cyclosporine (CYA) + MMF. Antilymphocyte induction therapy was allowed for up to 5 days. The primary endpoint of >/=3A rejection or hemodynamic compromise rejection requiring treatment showed no significant difference at 6 months (TAC/MMF 22.4%, TAC/SRL 24.3%, CYA/MMF 31.6%, p = 0.271) and 1 year (p = 0.056), but it was significantly lower in the TAC/MMF group when compared only to the CYA/MMF group at 1 year (23.4% vs. 36.8%; p = 0.029). Differences in the incidence of any treated rejection were significant (TAC/SRL = 35%, TAC/MMF = 42%, CYA/MMF = 59%; p < 0.001), as were median levels of serum creatinine (TAC/SRL = 1.5 mg/dL, TAC/MMF = 1.3 mg/dL, CYA/MMF = 1.5 mg/dL; p = 0.032) and triglycerides (TAC/SRL = 162 mg/dL, TAC/MMF = 126 mg/dL, CYA/MMF = 154 mg/dL; p = 0.028). The TAC/SRL group encountered fewer viral infections but more fungal infections and impaired wound healing. These secondary endpoints suggest that the TAC/MMF combination appears to offer more advantages than TAC/SRL or CYA/MMF in cardiac transplant patients, including fewer >/=3A rejections or hemodynamic compromise rejections and an improved side-effect profile.

  19. [Effects of mycophenolate mofetil in ischemic acute renal failure in rats].

    PubMed

    Chávez-Velásquez, M; Pons, H; Medina, M; Quiroz, Y; Parra, G; Herrera, J

    2007-01-01

    Mycophenolate mofetil (MMF) is a purine synthesis inhibitor commonly used as immunosupresive agent in transplantation. Kidney grafts undergo more or less prolonged cold ischemia after harvesting which results in variable degrees of ischemia reperfusion injury. To determine whether the inhibition of early events of cellular infiltration may influence the severity of damage induced by ischemic acute renal failure, 45 Sprague Dawley rats were given MMF at a dose of 20mg/kg/day (MMF-rats) by gavage 2 days before (pre-MMF group, n=15) or after (post-MMF group, n=15) clamping the left renal artery for 40 minutes followed by rigt-sided nephrectomy. (control group, n=15) received vehicle. Serum Creatinine (Screat) was measured daily in all groups. On the 2nd post-ischemic day Screat was significantly lower (p=0.001) in pre-MMF group compared with post-MMF group and control group (4 +/- 2mg/dl post-MMF group vs 1.7 +/- 1.2 mg/dl pre-MMF group, control group 5+/-2, p< 0.05). Kidney biopsies shown that the histologic damage was 54 +/- 28% in post-MMF group vs 34+/- 22% in pre-MMF group and 61 +/- 25% in control group (pre-MMF vs post-MMF, p NS). On the 5th day post-ischemic, MMF-rats showed more severe tubulointerstitial necrosis (pre-MMF group: 17 +/- 20 %, post-MMF group: 33 +/- 27%) than controls (4 +/- 5%). The severity of ATN was significantly higher in post-MMF group compared with controls (p=0.01). Tubulointersticial T-lymphocyte (T CD 5) and monocyte (ED 1) infiltration evaluated on the 2nd post-ischemic day was less intense in group I (T CD5: 3 +/- 3, ED 1: 10 +/- 9, cel/mm2) compared to post-MMF group (T CD 5: 10 +/- 4, ED 1: 55 +/- 40) and to control group (T CD 5: 10+/- 4, ED 1: 64 +/- 46). However, on the 5th post-ischemia day, ED 1 infiltration was significantly higher in post-MMF group (24 +/- 18%) compared to pre-MMF group (5 +/- 5, p NS) and also in pre-MMF group vs control group (31 +/- 33, p< 0.05). Our results suggest that MMF given before a renal ischemic

  20. Mycophenolate mofetil (MMF) does not slow the progression of subclinical atherosclerosis in SLE over 2 years.

    PubMed

    Kiani, Adnan N; Magder, Laurence S; Petri, Michelle

    2012-09-01

    Accelerated atherosclerosis is a major cause of mortality in SLE. Mycophenolate mofetil (MMF) has been shown to suppress growth factor-induced proliferation of vascular smooth muscle and endothelial cells in animal models. We hypothesized that MMF might modify the inflammatory component of atherosclerosis in SLE. We examined the effect of MMF on atherosclerosis as measured by changes in carotid intima-media thickness (IMT) or coronary artery calcium (CAC) over 2 years. CAC and carotid IMT were measured at baseline and 2 years later in a cohort of 187 patients with SLE. The cohort was 91% women, 59% Caucasian, and 35% African-American, with a mean age of 45 ± 11 years. Of these, 12.5% (n = 25) received MMF during follow-up. The daily dose ranged from 500 to 3,000 mg/day, and duration ranged from 84 days to the entire 2 years. We divided MMF users into three groups: low exposure (<1,500 mg average daily dose), high exposure (≥1,500 average daily dose), and any exposure of MMF (<1,500 or ≥1,500 average daily dose) for 2 years. The mean CAC increased in all four groups: no MMF: 1.17-1.28, low MMF: 1.02-1.13, high MMF: 1.44-1.61, and any MMF: 1.21-1.34 log-Agatston units. Compared to no MMF, there was no statistically different change between the three groups (p = 0.99, 0.87, and 0.91). Similarly, mean carotid IMT increased in all four groups: no MMF: 0.58-0.66, low MMF: 0.55-0.60, high MMF: 0.56-0.71, and any MMF: 0.56-0.66. We then adjusted for statin use, lupus nephritis, body mass index, systolic blood pressure, cholesterol, and age during the 2-year follow-up. The association between MMF exposure and change in CAC or carotid IMT was not statistically significant (p = 0.63 for CAC, and p = 0.085 for carotid IMT). There was no evidence that MMF slowed or decreased the progression of atherosclerosis as measured by carotid IMT or CAC. Because the number of patients taking MMF was only twenty-five, larger studies for longer time periods are needed to explore any

  1. Pharmacokinetic and pharmacodynamic analysis of inosine monophosphate dehydrogenase activity in hematopoietic cell transplantation recipients treated with mycophenolate mofetil.

    PubMed

    Li, Hong; Mager, Donald E; Sandmaier, Brenda M; Storer, Barry E; Boeckh, Michael J; Bemer, Meagan J; Phillips, Brian R; Risler, Linda J; McCune, Jeannine S

    2014-08-01

    A novel approach to personalizing postgrafting immunosuppression in hematopoietic cell transplantation (HCT) recipients is evaluating inosine monophosphate dehydrogenase (IMPDH) activity as a drug-specific biomarker of mycophenolic acid (MPA)-induced immunosuppression. This prospective study evaluated total MPA, unbound MPA, and total MPA glucuronide plasma concentrations and IMPDH activity in peripheral blood mononuclear cells (PMNCs) at 5 time points after the morning dose of oral mycophenolate mofetil (MMF) on day +21 in 56 nonmyeloablative HCT recipients. Substantial interpatient variability in pharmacokinetics and pharmacodynamics was observed and accurately characterized by the population pharmacokinetic-dynamic model. IMPDH activity decreased with increasing MPA plasma concentration, with maximum inhibition coinciding with maximum MPA concentration in most patients. The overall relationship between MPA concentration and IMPDH activity was described by a direct inhibitory maximum effect model with an IC50 of 3.23 mg/L total MPA and 57.3 ng/mL unbound MPA. The day +21 IMPDH area under the effect curve (AUEC) was associated with cytomegalovirus reactivation, nonrelapse mortality, and overall mortality. In conclusion, a pharmacokinetic-dynamic model was developed that relates plasma MPA concentrations with PMNC IMPDH activity after an MMF dose in HCT recipients. Future studies should validate this model and confirm that day +21 IMPDH AUEC is a predictive biomarker.

  2. Bioavailability of a new generic formulation of mycophenolate mofetil MMF 500 versus CellCept in healthy adult volunteers.

    PubMed

    Masri, M A; Rizk, S; Attia, M L E; Barbouch, H; Rost, M

    2007-05-01

    Several studies have revealed a decreased incidence of early graft rejection with the use of mycophenate mofetil (MMF). The cost of the drug is, however, prohibitive especially in developing countries with limited resources. We compared the pharmacokinetic profile of a new MMF generic formulation (MMF 500 batch number: 06T3001; Medis Tunis) with those of Cellcept, (batch number: M1427; Hoffmann La Roche, Switzerland) in healthy volunteers. The study was double-blinded to investigator and volunteers. It had a balanced randomized, two-treatment, two-period, two-sequence, single-dose, crossover, comparative oral bioavailability design in adult healthy human volunteers. The study was designed, performed, and monitored by CRO Transmedical s.a.l International (Beirut, Lebanon) in accordance with the Basic Principals defined in the US 21 CFR Part 312.20, and the principals enunciated in the World Medical Association Declaration of Helsinki. We included nonsmoking healthy volunteers between the ages of 22 and 45 years. The subjects were admitted to the hospital one night prior to blood sampling. After volunteers received the same dinner, they were fasted overnight and for 2 hours postdosing. At 8 am each person received a single oral dose of 500 mg of either formulation. Blood samples were collected to construct the pharmacokinetic profiles as follows: 0, 0.15, 0.30, 0.45 minutes and 1, 1.15, 1.30, 2, 4, 6, 10, 12, and 24 hours. Water and food intake were the same for all volunteers during the whole study period. Following an 8-day washout period, the subjects were crossed over. Plasma mycophenolic acid concentrations were determined using a high-performance liquid chromatography validated enzyme-linked immunosorbent assay-based method (TransMedical, Beirut Lebanon). Physical examinations, hematology, urinanalysis, serum chemistry tests, and liver enzymes were performed at screening and at the end of each period. Subjects were monitored for safety and adverse events

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

    PubMed

    Madrakian, Tayyebeh; 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 0.87V and 1.1V vs. Ag/AgCl for MPM and an oxidation peak at 0.87V vs. Ag/AgCl for MPA in phosphate buffer solution of pH5.0. 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(-6) to 1.6×10(-4)molL(-1) and 2.5×10(-6)molL(-1) to 6.0×10(-5)molL(-1) for MPM and MPA, respectively. The detection limit was found to be 9.0×10(-7)molL(-1) and 4.0×10(-7)molL(-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.

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

    PubMed Central

    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

    2015-01-01

    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. PMID:26561804

  5. Impact of mycophenolate mofetil (MMF)-related gastrointestinal complications and MMF dose alterations on transplant outcomes and healthcare costs in renal transplant recipients.

    PubMed

    Tierce, J C; Porterfield-Baxa, J; Petrilla, A A; Kilburg, A; Ferguson, R M

    2005-12-01

    Mycophenolate mofetil (MMF), a mycophenolic acid prodrug, is a highly effective adjunct immunosuppressive agent in transplant therapy. Although MMF is generally well tolerated, optimal therapy may be limited by adverse effects, in particular gastrointestinal (GI) toxicity, which has been reported to occur in up to 45% of MMF-treated patients. MMF dose changes resulting from these adverse events may lead to sub-therapeutic dosing and impaired clinical outcomes. This retrospective study analyzed clinical records from 772 renal transplant patients from 10 US transplant centers who were initiated on MMF. The analysis revealed that 49.7% (n = 382) of patients experienced at least one GI complication within the first 6 months post-transplant, with 66.8% (n = 255) of these having multiple GI complications. Of the patients with GI complications, 39.0% experienced MMF dose adjustments or discontinuation of MMF therapy. Patients with GI complications who experienced MMF dose adjustments/discontinuation had a significantly increased incidence of acute rejections compared with patients without GI complications (30.2% vs. 19.4%; p = 0.005). Mean treatment costs were higher in patients with GI complications than in those with no GI complications, particularly in those who experienced MMF dose adjustments/discontinuation (p = 0.0001). The mean incremental cost for patients experiencing GI complications was US$3700 per patient during the 6 months post-transplant (p < 0.001), which was mainly attributable to hospitalization costs. In summary, GI complications and MMF dose adjustments/discontinuations are associated with a significant negative impact on transplant outcomes and markedly increase short-term treatment costs.

  6. Development and validation of limited sampling strategy equation for mycophenolate mofetil in children with systemic lupus erythematosus

    PubMed Central

    Prabha, R.; Mathew, B. S.; Jeyaseelan, V.; Kumar, T. S.; Agarwal, I.; Fleming, D. H.

    2016-01-01

    The aim of this study was to establish a limited sample strategy (LSS) to predict the mycophenolic acid (MPA) area under the curve (AUC)(0-12) in children with systemic lupus erythematosus (SLE). Three months after initiation of mycophenolate mofetil (MMF) 26 children with SLE presented for therapeutic drug monitoring of MPA. On the day of the test, 10 specimens were collected, analyzed, and MPA AUC(0-12) was calculated. Using step-wise regression analysis, LSS equations were developed. Using bootstrap validation, the predictive performance was calculated. The measured mean (standard deviation) for the trough concentration and AUC(0-12) were 2.55 (1.57) μg/ml and 62.6 (21.67) mg.h/L, respectively. The range of trough concentrations and AUC(0-12) were 0.7–5.54 μg/ml and 22.1–104.8 mg.h/L, respectively. The interindividual variability (%CV) for dose normalized AUC(0-12) and dose normalized Ctrough was 46.5% and 61.1%, respectively. The correlation between the concentrations at the different time points and MPA AUC(0-12) ranged from 0.05 (1.5 h) to 0.56 (4 h). Two LSS equations that included 4 or 5 time points up to 3 h were developed and validated. The 4 point LSS had a correlation (R2) of 0.88 and the 5 point LSS an R2 of 0.87. With respect to the 4 point and 5 point MPA LSS AUC(0-12), the bias was 1.92% and 1.96%, respectively, and the imprecision was 11.24% and 11.28%, respectively. A 4 point LSS which concludes within 3 h after the administration of the MMF dose was developed and validated, to determine the MPA AUC(0-12) in children with SLE. PMID:27942171

  7. Beneficial effect of the inosine monophosphate dehydrogenase inhibitor mycophenolate mofetil on survival and severity of glomerulonephritis in systemic lupus erythematosus (SLE)-prone MRLlpr/lpr mice

    PubMed Central

    Jonsson, C A; Svensson, L; Carlsten, H

    1999-01-01

    The aim of the present study was to evaluate the therapeutic effect of mycophenolate mofetil (MMF) on the course of disease in SLE-prone MRLlpr/lpr mice. Three-months-old mice displaying clinical symptoms of glomerulonephritis were given MMF (100 mg/kg per day) orally via the drinking water. Control mice received i.p. injections of cyclophosphamide (CYC) (1.8 mg/mouse per week) or saline. Survival, albuminuria and haematuria, immunoglobulin levels and anti-dsDNA antibodies in serum, frequencies of immunoglobulin-producing B lymphocytes and glomerular deposits of immunoglobulin and C3 were analysed. The results showed that MMF treatment significantly prolonged survival and reduced the occurrence of albuminuria and haematuria in MRLlpr/lpr mice. In addition, the number of immunoglobulin-producing B cells and serum levels of IgG and IgG anti-dsDNA antibodies were reduced after MMF and CYC treatment. MMF treatment significantly reduced the extent of deposition of C3 in glomeruli. We conclude that the reduced severity of glomerulonephritis following treatment of lupus-prone mice with MMF was as efficacious as that of CYC. These results warrant clinical trials of MMF in SLE patients with glomerulonephritis. PMID:10361247

  8. The effect of mycophenolate mofetil on disease development in the gld.apoE (-/-) mouse model of accelerated atherosclerosis and systemic lupus erythematosus.

    PubMed

    Richez, Christophe; Richards, Rocco J; Duffau, Pierre; Weitzner, Zachary; Andry, Christopher D; Rifkin, Ian R; Aprahamian, Tamar

    2013-01-01

    Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that is characterized by autoantibody production and inflammatory disease involving multiple organs. Premature atherosclerosis is a common complication of SLE and results in substantial morbidity and mortality from cardiovascular disease (CVD). The reasons for the premature atherosclerosis in SLE are incompletely understood, although chronic inflammation is thought to play an important role. There is currently no known preventative treatment of premature atherosclerosis in SLE. Mycophenolate mofetil (MMF) is an immunosuppressive agent that is commonly used for treatment of patients with SLE. In order to study the impact of this drug on murine lupus disease including premature atherosclerosis development, we treated gld.apoE(-/-) mice, a model of SLE and accelerated atherosclerosis, with MMF. We maintained seven-week old gld.apoE(-/-) mice on a high cholesterol Western diet with or without MMF. After 12 weeks on diet, mice receiving MMF showed decreased atherosclerotic lesion area compared to the control group. MMF treatment also improved the lupus phenotype, indicated by a significant decrease circulating autoantibody levels and ameliorating lupus nephritis associated with this model. This data suggests that the effects of MMF on the immune system may not only be beneficial for lupus, but also for inflammation driving lupus-associated atherosclerosis.

  9. A Pilot Study of Continuous Infusion of Mycophenolate Mofetil for Prophylaxis of Graft-versus-Host-Disease in Pediatric Patients.

    PubMed

    Windreich, Randy M; Goyal, Rakesh K; Joshi, Rujuta; Kenkre, Tanya S; Howrie, Denise; Venkataramanan, Raman

    2016-04-01

    Mycophenolate mofetil (MMF), an ester prodrug of mycophenolic acid (MPA), is used increasingly for graft-versus-host disease (GVHD) prophylaxis. Empiric fixed-dose-escalation strategies in pediatric hematopoietic cell transplantation (HCT) recipients have failed to achieve target MPA exposure. We evaluated the safety and feasibility of a pharmacokinetics-based dosing approach using a novel continuous infusion (CI) method of administration of MMF in pediatric HCT recipients. All patients received a myeloablative conditioning with cyclosporine A and MMF for GVHD prophylaxis. MMF was initiated on day 0 at a dose of 15 mg/kg every 8 hours. Based on steady-state pharmacokinetics, MMF was converted to CI to target a total MPA AUC(0-24) of 40 to 80 μg·hour/mL. The MMF dose was adjusted to maintain a total MPA steady-state concentration (Css) of 1.7 to 3.3 μg/mL. During the CI schedule, MPA AUC(0-24) was maintained at a mean of 40.1 μg·hour/mL (range, 20.6 to 63.8), and 17 of 19 patients (89%) achieved MPA Css within target of 1.7 to 3.3 μg/mL. Eighteen of 19 patients (95%) achieved neutrophil engraftment at a median of 13 days (range, 8 to 41) post-transplant and platelet engraftment at 39 days (range, 17 to 298) days post-transplant. Six of 18 assessable patients (33%) developed stages II to IV acute GVHD and 2 of 15 (13%) developed chronic GVHD. The MMF dose was reduced in 9 patients due to gastrointestinal symptoms (n = 6), low blood counts (n = 4), and viral infection (n = 3). Five patients with acute lymphoblastic leukemia relapsed, of whom 4 have died. Fifteen of 19 patients are alive with a median follow-up of 2.4 years (range, .4 to 4.9), with 3-year event-free and overall survival rates of 68% and 79%, respectively. In this pilot study of pharmacokinetically directed MMF dosing, we observed no toxic deaths, excellent engraftment, and low rates of grades III to IV acute and chronic GVHD. We found significantly lower half-life and higher drug clearance in

  10. Cardiovascular morbidity and mortality after liver transplantation: The protective role of Mycophenolate Mofetil.

    PubMed

    D'Avola, D; Cuervas-Mons, V; Martí, J; Ortiz de Urbina, J; Lladó, L; Jimenez, C; Otero, E; Suarez, F; Rodrigo, J M; Gómez, M A; Fraga, E; Lopez, P; Serrano, T; Rios, A; Fábrega, E; Herrero, J I

    2017-02-03

    Cardiovascular (CV) diseases are recognized long-term causes of death after liver transplantation (LT). The objective of this multicenter study was to analyse the prevalence and the evolution of CV risk factors and CV morbidity and mortality in 1819 liver transplant recipients along 5 years after LT. The influence of baseline variables on survival, morbidity and mortality was studied. There was a continuous and significant increase of the prevalence of all the CV risk factors (except smoking) after LT. CV diseases were the fourth cause of mortality in the 5 years after LT, causing 12% of deaths during the follow-up. Most CV events (39%) occurred in the first year after LT. Pre-existing CV risk factors such as age, pre-LT CV events, diabetes, metabolic syndrome and hyperuricemia, and mycophenolate-free immunosuppressive therapy, increased post-LT CV morbidity and mortality. The development of new onset CV risk factors after LT, such as dyslipidemia and obesity, independently affected late CV morbidity and mortality. Tacrolimus and steroids increased the risk of post-transplant diabetes, while cyclosporine increased the risk of arterial hypertension dyslipidemia and metabolic syndrome.

  11. Effects of mycophenolate mofetil introduction in liver transplant patients: results from an observational, non-interventional, multicenter study (LOBSTER).

    PubMed

    Schlitt, Hans J; Jonas, Sven; Ganten, Tom M; Grannas, Gerrit; Moench, Christian; Rauchfuss, Falk; Obed, Aiman; Tisone, Giuseppe; Pinna, Antonio D; Gerunda, Giorgio E; Beckebaum, Susanne

    2013-01-01

    The benefits of calcineurin inhibitor (CNI)-sparing regimens on renal function following liver transplantation (LT) have been demonstrated in clinical studies. This observational study assessed the real-life effects of mycophenolate mofetil (MMF) introduction in LT patients. Four hundred and ninety-seven patients in whom MMF was introduced according to local standards or clinical considerations were entered. Patients were grouped by time between transplantation and start of MMF (start of study): Group A (n = 263): ≤6 d; Group B (n = 64): >6 d to ≤1 month; Group C (n = 74): >1 month to ≤1 yr; and Group D (n = 96): >1 yr. CNI sparing occurred in all groups, particularly in Groups C and D. Mean MMF doses at 12 months were 1202.7, 1363.5, 1504.7, and 1578.1 mg/d, respectively, in Groups A-D. At introduction of MMF, median glomerular filtration rate was 73.3, 81.7, 62.7, and 53.7 mL/min/1.73 m(2) in Groups A-D. At 12 months, this decreased to 66 mL/min/1.73 m(2) in Groups A and B, remained stable in Group C, and increased in Group D (64.8 mL/min/1.73 m(2) ). Serious adverse drug reactions were lowest in Group D. In conclusion, MMF with a subsequent decrease in CNI was well tolerated and improved renal function even years after transplantation. A more forceful MMF dosing strategy with greater CNI sparing may further improve renal function.

  12. Efficacy and safety of a conversion from the original tacrolimus and mycophenolate mofetil to the generics Tacpan® and Mowel® after liver transplantation

    PubMed Central

    Vollmar, Johanna; Bellmann, Maren Christina; Darstein, Felix; Hoppe-Lotichius, Maria; Mittler, Jens; Heise, Michael; Rüttger, Bernd; Weyer, Veronika; Zimmermann, Anca; Lang, Hauke; Galle, Peter R; Zimmermann, Tim

    2015-01-01

    Background Expensive pharmaceuticals are a major reason for cost intensive health care systems. Long-term immunosuppressive therapy plays a relevant role after organ transplantation. Patents of original drugs have expired and cheaper products are available. Little data are available regarding efficacy and safety of generic immunosuppressive agents. Methods In this prospective study, 25 patients, who were clinically stable for a minimum of 2 years after liver transplantation, were converted from the original formulations of tacrolimus (TAC) and mycophenolate mofetil to the generics Tacpan® (TAP) and Mowel® (MOW). Patients were followed-up for 6 months. Results were compared retrospectively to 25 age- and sex-matched controls treated with the original brands. Results In the matched-pair analysis of TAC trough level/dose ratio, no significant difference was found between TAP/MOW and TAC/mycophenolate mofetil groups. No acute rejection occurred in either group. In total, 17 patients reported mild side effects in the TAP/MOW group. The most common side effects were gastrointestinal symptoms. Intra-individual analysis of costs revealed a considerable cost reduction in the TAP/MOW group (in median 25.03%; P<0.001). Conclusion In summary, the use of the generics TAP/MOW is effective and seems to be safe and cost-efficient in stable liver-transplantation patients. PMID:26604701

  13. Mycophenolate Mofetil for Induction and Maintenance of Remission in Microscopic Polyangiitis with Mild to Moderate Renal Involvement—A Prospective, Open-Label Pilot Trial

    PubMed Central

    Silva, Francisco; Specks, Ulrich; Kalra, Sanjay; Hogan, Marie C.; Leung, Nelson; Sethi, Sanjeev

    2010-01-01

    Background and objectives: Microscopic polyangiitis (MPA) is a systemic small-vessel vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCA), often targeting myeloperoxidase (MPO). Cyclophosphamide (CYC) plus corticosteroids (CS) is considered standard therapy for patients with renal involvement, but treatment response is not satisfactory in all patients and CYC has well recognized toxicity. This prospective pilot trial explored whether mycophenolate mofetil (MMF) represents an effective alternative to CYC for induction and maintenance of remission in MPA with mild to moderate renal involvement. Design, setting, participants, & measurements: Seventeen P-ANCA/MPO-ANCA-positive patients with MPA with mild to moderate renal involvement received MMF (1000 mg orally, twice daily) and CS (intravenous methylprednisolone, 1 to 3 g, followed by oral prednisone at 1 mg/kg per day). Oral CS were discontinued by month 6; MMF was continued through month 18. The primary outcome measure was remission by month 6 and stable renal function. Secondary endpoints included major relapses necessitating a switch to CYC plus CS, minor relapses requiring an increase in CS dosage, and adverse events. Results: Thirteen of 17 patients enrolled achieved the primary outcome, and 4 failed because of insufficient response, relapse, or MMF intolerance. Twelve patients remained in remission through month 18, renal function remained stable, and proteinuria improved. Side effects of MMF were mild, transient, and responsive to dose adjustments in all patients except one. Conclusions: MMF represents an alternative to CYC for induction and maintenance of remission in patients with MPO-ANCA-associated MPA with mild to moderate renal disease. PMID:20093349

  14. A randomized controlled trial of mycophenolate mofetil in patients with IgA nephropathy [ISRCTN62574616

    PubMed Central

    Hogg, Ronald J; Wyatt, Robert J

    2004-01-01

    Background IgAN is the most common type of glomerulonephritis in the world. Between 15 and 40 percent of adults and children diagnosed with IgAN eventually progress to ESRD. Despite the need for effective treatment strategies, very few RCTs for IgAN have been performed. The most effective therapies for IgAN appear to be corticosteroids, ACEi, and FOS that contain a high concentration of omega 3 fatty acids. While ACEi and FOS are generally well tolerated with minimal side effects, the use of high dose steroids over a long course of therapy is often associated with significant morbidity. Objective of the study The objective of the study is to test the hypothesis that treatment with the immunosuppressive agent, MMF, will lead to significant and sustained improvement in urinary protein excretion in patients with IgAN who have been pre-treated (and continue to be treated) with ACEi and FOS compared to a placebo control group of patients receiving comparable doses of ACEi and FOS without MMF. Design After a three month treatment period with the ACEi, lisinopril and the FOS, Omacor®, 100 (2 × 50) patients with IgAN and a urinary P/C ratio ≥ 0.6 (males) and ≥ 0.8 (females) and an estGFR ≥ 40 ml/min/1.73 m2 will be randomized to treatment with either MMF or placebo for one year. All patients will be followed off study drug for a second year, but will continue treatment with lisinopril and Omacor® for the two year duration of the study. The primary outcome measure of change in urine P/C ratio will be assessed at the end of years one and two. PMID:15043759

  15. Congenital Diaphragmatic Hernia and Microtia in a Newborn with Mycophenolate Mofetil (MMF) Exposure: Phenocopy for Fryns Syndrome or Broad Spectrum of Teratogenic Effects?

    PubMed Central

    Parisi, Melissa A.; Zayed, Hatem; Slavotinek, Anne M.; Rutledge, Joe C.

    2009-01-01

    A newborn female infant born to a woman on immunosuppressive medications including mycophenolate mofetil (MMF) for a renal graft secondary to lupus nephritis presented with congenital diaphragmatic hernia (CDH) and additional findings of microtia, esophageal atresia with tracheoesophageal fistula, cleft palate, congenital heart defect, digital anomalies, and dysmorphic facial features. Pulmonary hypoplasia resulted in death at day two of life. She was presumed to have Fryns syndrome based on diagnostic criteria established for this recessive disorder with prominent features including CDH, facial anomalies, and nail hypoplasia. In retrospect, this infant's findings are more likely the result of teratogenic exposure to MMF, as more recent data have emerged linking aural atresia, digital anomalies, and dysmorphic features to this drug. To date, this is the only human report of CDH in an infant with prenatal exposure to MMF, although the manufacturer's package insert alludes to animal studies with a broad spectrum of malformations, including CDH. Thus, a teratogenic exposure can mimic a known Mendelian genetic syndrome, and caution is urged in presuming a genetic etiology for infants with potential teratogenic exposure to relatively new drugs with limited published animal data. PMID:19449404

  16. Congenital diaphragmatic hernia and microtia in a newborn with mycophenolate mofetil (MMF) exposure: phenocopy for Fryns syndrome or broad spectrum of teratogenic effects?

    PubMed

    Parisi, Melissa A; Zayed, Hatem; Slavotinek, Anne M; Rutledge, Joe C

    2009-06-01

    A newborn female infant born to a woman on immunosuppressive medications including mycophenolate mofetil (MMF) for a renal graft secondary to lupus nephritis presented with congenital diaphragmatic hernia (CDH) and additional findings of microtia, esophageal atresia with tracheoesophageal fistula, cleft palate, congenital heart defect, digital anomalies, and dysmorphic facial features. Pulmonary hypoplasia resulted in death at day 2 of life. She was presumed to have Fryns syndrome based on diagnostic criteria established for this recessive disorder with prominent features including CDH, facial anomalies, and nail hypoplasia. In retrospect, this infant's findings are more likely the result of teratogenic exposure to MMF, as more recent data have emerged linking aural atresia, digital anomalies, and dysmorphic features to this drug. To date, this is the only human report of CDH in an infant with prenatal exposure to MMF, although the manufacturer's package insert alludes to animal studies with a broad spectrum of malformations, including CDH. Thus, a teratogenic exposure can mimic a known Mendelian genetic syndrome, and caution is urged in presuming a genetic etiology for infants with potential teratogenic exposure to relatively new drugs with limited published animal data.

  17. A critical analysis of racial difference with mycophenolate mofetil (MMF) dosing, clinical outcomes and adverse effects in pediatric kidney transplant patients.

    PubMed

    Jensen, C J; Shrivastava, S; Taber, D J; Weimert, N A; Shatat, I F; Orak, J; Chavin, K D; Baliga, P K

    2011-01-01

    There is paucity in the data examining the differences in mycophenolate mofetil (MMF) dosing and outcomes among pediatric kidney transplant recipients (PKTX) between races. The aims of this study were as follows (i) to assess whether higher doses of MMF are being utilized in African American (AA) PKTX (ii) to determine whether there is a correlation between MMF dose and outcomes between races, and (iii) to assess the adverse effects of MMF between races. This study analyzed 109 PKTX who received MMF between 7/99 and 5/08. Demographics were similar between groups. Fewer AAs received kidneys from living donors (18% vs. 44%), spent more time on dialysis (1.0 vs. 0.5 yr), and had more human leukocyte antigen mismatches (4 vs. 3). MMF doses among AA patients were higher throughout the study, with statistical differences at week 4, month 3, and month 18. AA patients had significantly higher acute rejection rates and trended toward poorer graft survival; infections, adverse events from MMF and post-transplant lymphoproliferative disease tended to be lower in the AA patients. AA PKTX received higher MMF doses within the first three yr post-transplant compared to their non-AA counterparts, yet demonstrate significantly more acute rejection episodes. Importantly, MMF caused fewer adverse events in AA patients, despite these patients receiving higher doses.

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

    PubMed

    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.

  19. Pharmacokinetic modelling and development of Bayesian estimators for therapeutic drug monitoring of mycophenolate mofetil in reduced-intensity haematopoietic stem cell transplantation

    PubMed Central

    Saint-Marcoux, Franck; Royer, Bernard; Debord, Jean; Larosa, Fabrice; Legrand, Faezeh; Deconinck, Eric; Kantelip, Jean-Pierre; Marquet, Pierre

    2009-01-01

    Background Mycophenolate mofetil (MMF), a prodrug of mycophenolic acid (MPA), is used during nonmyeloablative and reduced-intensity conditioning haematopoetic cell transplantation (HCT) to improve engraftment and reduce graft versus host disease (GVHD). However, information about MPA pharmacokinetics is sparse in this context and its use is still empirical. Objectives To perform a pilot pharmacokinetic study and to develop maximum a posteriori Bayesian estimators (MAP-BEs) for the estimation of MPA exposure in HCT. Patients and methods Fourteen patients given orally MMF 15 mg/kg 3 times daily were included. Two consecutive 8-hour PK profiles were performed the same day respectively three days before and 4 days after the HCT. One 8-hour PK profile was performed on day 27 after transplantation. For these 8-hours pharmacokinetic profiles, blood samples were collected pre-dose and 20, 40, 60, 90 min, 2, 4, 6 and 8 h post-dose after administration of the drug. Using the iterative two-stage method (ITS), two different one-compartment open PK models with first-order elimination were developed to describe the data: one with two gamma laws and one with three gamma laws to describe the absorption phase. For each PK profile, the Akaike criterion was calculated to evaluate model fitting. On the basis of the population PK parameters, MAP-BEs were developed for the estimation of MPA pharmacokinetics and area under the concentration-time curves (AUC0-8h) at the different studied periods using a limited sampling strategy (LSS). These MAP-BEs were then validated using a data-splitting method. Results The ITS approach allowed the development of MAP-BEs based either on “double-gamma” or “triple-gamma” models, the combination of which allowed correct estimation of MPA pharmacokinetics and AUC on the basis of a C20min-C90min-C240min sampling schedule. The mean bias of the Bayesian versus reference (trapezoidal) AUCs was <5% with less than 16% of the patients with absolute bias

  20. Long-term follow-up of the MAINTAIN Nephritis Trial, comparing azathioprine and mycophenolate mofetil as maintenance therapy of lupus nephritis

    PubMed Central

    Tamirou, Farah; D'Cruz, David; Sangle, Shirish; Remy, Philippe; Vasconcelos, Carlos; Fiehn, Christoph; Ayala Guttierez, Maria del Mar; Gilboe, Inge-Magrethe; Tektonidou, Maria; Blockmans, Daniel; Ravelingien, Isabelle; le Guern, Véronique; Depresseux, Geneviève; Guillevin, Loïc; Cervera, Ricard; Houssiau, Frédéric A

    2016-01-01

    Objective To report the 10-year follow-up of the MAINTAIN Nephritis Trial comparing azathioprine (AZA) and mycophenolate mofetil (MMF) as maintenance therapy of proliferative lupus nephritis, and to test different definitions of early response as predictors of long-term renal outcome. Methods In 2014, data on survival, kidney function, 24 h proteinuria, renal flares and other outcomes were collected for the 105 patients randomised between 2002 and 2006, except in 13 lost to follow-up. Results Death (2 and 3 in the AZA and MMF groups, respectively) and end-stage renal disease (1 and 3, respectively) were rare events. Time to renal flare (22 and 19 flares in AZA and MMF groups, respectively) did not differ between AZA and MMF patients. Patients with good long-term renal outcome had a much more stringent early decrease of 24 h proteinuria compared with patients with poor outcome. The positive predictive value of a 24 h proteinuria <0.5 g/day at 3 months, 6 months and 12 months for a good long-term renal outcome was excellent (between 89% and 92%). Inclusion of renal function and urinalysis in the early response criteria did not impact the value of early proteinuria decrease as long-term prognostic marker. Conclusions The long-term follow-up data of the MAINTAIN Nephritis Trial do not indicate that MMF is superior to AZA as maintenance therapy in a Caucasian population suffering from proliferative lupus nephritis. Moreover, we confirm the excellent positive predictive value of an early proteinuria decrease for long-term renal outcome. Trial registration number NCT00204022. PMID:25757867

  1. Comparison of cyclosporine and tacrolimus combined with mycophenolate mofetil in prophylaxis for graft-versus-host disease after reduced-intensity umbilical cord blood transplantation.

    PubMed

    Miyamoto, Toshihiro; Takashima, Shuichiro; Kato, Koji; Takase, Ken; Yoshimoto, Goichi; Yoshida, Shuro; Henzan, Hideho; Osaki, Koichi; Kamimura, Tomohiko; Iwasaki, Hiromi; Eto, Tetsuya; Teshima, Takanori; Nagafuji, Koji; Akashi, Koichi

    2017-01-01

    Umbilical cord blood transplantation with a reduced-intensity conditioning regimen (RIC-UCBT) is used increasingly in patients who have comorbid organ functions and lack human leukocyte antigen-identical donors. We compared the outcomes in 35 patients who received mycophenolate mofetil plus cyclosporine (MMF/CSP, n = 17) or MMF plus tacrolimus (MMF/TAC, n = 18) for graft-versus-host disease (GVHD) prophylaxis after RIC-UCBT. Cumulative incidence of neutrophil engraftment was 94 and 89 % in MMF/CSP and MMF/TAC groups, respectively (p = 0.34). The incidence of pre-engraftment immune reaction did not differ between the MMF/CSP (41 %) and MMF/TAC (39 %, p = 1.00) groups; however, patients in the MMF/TAC group tended to have a lower incidence of grade II-IV acute GVHD than those in MMF/CSP group (28 vs 53 %, p = 0.11). Overall survival (OS) at 1 year was 43 and 60 % in MMF/CSP and MMF/TAC groups, respectively (p = 0.39). Progression-free survival, non-relapse mortality, and relapse rate were comparable between the two groups (p = 0.76, 0.59, and 0.88, respectively). In multivariate analyses, MMF/TAC GVHD prophylaxis was closely associated with improved OS, but not with incidence of engraftment and acute GVHD. These results suggest that more intensive GVHD prophylaxis with MMF/TAC decreased acute GVHD without affecting other clinical outcomes, resulting in improved OS after RIC-UCBT.

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

    PubMed

    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.

  3. A PROSPECTIVE RANDOMIZED TRIAL OF TACROLIMUS AND PREDNISONE VERSUS TACROLIMUS, PREDNISONE AND MYCOPHENOLATE MOFETIL IN PRIMARY ADULT LIVER TRANSPLANTATION: A SINGLE CENTER REPORT1

    PubMed Central

    Jain, A.; Kashyap, R.; Dodson, F.; Kramer, D.; Hamad, I.; Khan, A.; Eghestad, B.; Starzl, T.E.; Fung, J.J.

    2010-01-01

    Background Tacrolimus (TAC) and mycophenolate mofetil (MMF) are currently approved immunosuppressants for prevention of rejection in liver transplantation (LTx). They have different modes of action and toxicity profiles, but the efficacy and safety of MMF in primary liver transplantation with TAC has not been determined. Methods An Institutional Review Board-approved, open-label, single-center, prospective randomized trial was initiated to study the efficacy and toxicity of TAC and steroids (double-drug therapy (D)) versus TAC, steroids, and MMF (triple-drug therapy (T)) in primary adult LTx recipients. Both groups of patients were started on the same doses of TAC and steroids. Patients randomized to T also received 1 gm MMF twice a day. Results Between August 1995 and May 1998, 350 patients were enrolled at a single center-175 in the D and 175 in the T groups. All patients were followed until May 1998, with a mean follow-up of 33.8±9.1 months. Using an intention-to-treat analysis, the 1-, 2-, 3-, and 4-year patient survival was 85.1%, 81.6%, 78.6%, and 75.8%, respectively, for D and 87.4%, 85.4%, 81.3%, and 79.9%, respectively, for T. The 4-year graft survival was 70% for D and 72.1% for T. Although the rate of acute rejection in the first 3 months was significantly lower for T than for D (28% for triple vs. 38.9% for double, P=0.03), the overall rate of rejection for T at the end of 1 year was not significantly lower than for the D (38.9% triple vs. 45.2% double). The median time to the first episode of rejection was 14 days for D versus 24 days for T (P=0.008). During the study period, 38 of 175 patients in D received MMF to control ongoing acute rejection, nephrotoxicity, and/or neurotoxicity. On the other hand, 103 patients in the T discontinued MMF for infection, myelosuppression, and/or gastrointestinal disturbances. The need for corticosteroids was less after 6 months for T and the perioperative need for dialysis was lower with use of MMF. Conclusion This

  4. A case of acute humoral rejection in liver transplantation: successful treatment with plasmapheresis and mycophenolate mofetil.

    PubMed

    Rostron, Anthony; Carter, Vaughan; Mutunga, Mbithe; Cavanagh, Gary; O'Suilleabhain, Criostoir; Burt, Alistair; Jaques, Bryon; Talbot, David; Manas, Derek

    2005-11-01

    We present a case of a 23-year-old female who underwent orthotopic liver transplantation (OLTx) for biliary atresia, 22 years after a failed Kasai operation. Unusually, her postoperative course was complicated by severe acute humoral rejection. In this case report, we discuss her management as well as the role of plasmapheresis in treating allograft dysfunction secondary to acute humoral rejection in liver transplant patients.

  5. Exploratory research for optimal GvHD prophylaxis after single unit CBT in adults: short-term methotrexate reduced the incidence of severe GvHD more than mycophenolate mofetil.

    PubMed

    Terakura, S; Wake, A; Inamoto, Y; Murata, M; Sakai, R; Yamaguchi, T; Takahashi, S; Uchida, N; Onishi, Y; Ohashi, K; Ozawa, Y; Kanamori, H; Yamaguchi, H; Fukuda, T; Ichinohe, T; Takanashi, M; Atsuta, Y; Teshima, T

    2017-03-01

    In order to examine GvHD prophylaxis in umbilical cord blood transplantation (UCBT) in more detail, we compared transplant outcomes after UCBT for acute leukemia among GvHD prophylaxes using registry data. We selected patients transplanted with a calcineurin inhibitor and methotrexate (MTX)/mycophenolate mofetil (MMF) combination. A total of 1516 first myeloablative UCBT between 2000 and 2012 (Cyclosporine A (CyA) plus MTX, 824, Tacrolimus (Tac) plus MTX, 554, Tac plus MMF, 138) were included. With adjusted analyses, Tac plus MMF showed a significantly higher risk for grade II-IV and III-IV acute GvHD than CyA or Tac plus MTX. Although NRM was similar, Tac plus MMF showed a significantly lower risk of relapse than CyA or Tac plus MTX. A significant difference was observed in the risk of overall mortality (OM) between the MTX-containing group and MMF-containing group. In patients with standard-risk disease, there was no significant difference in the risk of OM in any GvHD prophylaxis. However, in patients with advanced-risk disease, Tac plus MMF showed a significantly lower risk of OM. Therefore, MTX-containing prophylaxis is preferred in UCBT for standard-risk disease, whereas MMF-containing prophylaxis is preferred for advanced-risk disease. A prospective study to identify optimal GvHD prophylaxis for UCBT is warranted.

  6. Fludarabine and Total-Body Irradiation Followed By Donor Stem Cell Transplant and Cyclosporine and Mycophenolate Mofetil in Treating HIV-Positive Patients With or Without Cancer

    ClinicalTrials.gov

    2015-08-28

    Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Essential Thrombocythemia; Extramedullary Plasmacytoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; HIV Infection; HIV-associated Hodgkin Lymphoma; Intraocular Lymphoma; Isolated Plasmacytoma of Bone; Juvenile Myelomonocytic Leukemia; Mast Cell Leukemia; Meningeal Chronic Myelogenous Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Myeloid/NK-cell Acute Leukemia; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Polycythemia Vera; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Primary Central Nervous System Lymphoma; Primary Myelofibrosis; Primary Systemic Amyloidosis; Progressive Hairy Cell Leukemia, Initial Treatment; Prolymphocytic Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lymphoma

  7. Clinical pharmacokinetics and pharmacodynamics of mycophenolate in patients with autoimmune disease.

    PubMed

    Abd Rahman, Azrin N; Tett, Susan E; Staatz, Christine E

    2013-05-01

    polymorphisms in genes encoding uridine diphosphate glucuronosyltransferase were identified in some studies as having a significant influence on the pharmacokinetics of mycophenolate. Typical MPA CL/F values in autoimmune disease patients were generally slightly lower than values published previously in population pharmacokinetic studies involving renal allograft recipients, possibly because of usage of ciclosporin, poorer renal function or lower serum albumin levels in the renal transplant cohort. In a single crossover study involving ten subjects only, significantly higher MPA AUC12 and maximum MPA concentration (C max) and lower MPA CL/F were reported following EC-MPS administration compared to mycophenolate mofetil administration. MPA exposure correlated well with treatment efficacy in patients with autoimmune disease (response to treatment, active disease and disease markers); however the relationship between MPA exposure and adverse events (infectious episodes, haematological toxicity and gastrointestinal symptoms) was unclear. Further investigation is required in autoimmune diseases such as chronic plaque psoriasis and rheumatoid arthritis and following EC-MPS administration. The extent of within-subject variability in the pharmacokinetics of mycophenolate is largely unknown and potential covariate influences need to be confirmed in studies with large subject numbers. A relationship between MPA and MPA metabolite exposure and toxicity needs to be established. The contribution of pharmacogenetics to the pharmacokinetics and pharmacodynamics of mycophenolate warrants further investigation, as does the utility of therapeutic drug monitoring. Dosing to achieve a target MPA AUC12 >35 mg·h/L is likely to lead to better efficacy outcomes in patients with autoimmune disease (rather than just giving standard doses, which lead to a wide range of exposures). However, the relationship between mycophenolate exposure and toxicity requires further investigation to determine the upper

  8. Long-term mycophenolate monotherapy in human leukocyte antigen (HLA)-identical living-donor kidney transplantation

    PubMed Central

    2014-01-01

    Methods We analyzed all PRA-negative patients who received a first kidney transplant from an HLA-identical living donor. The patients received no antibody induction. An intraoperative bolus of 500 mg of methylprednisolone was administered. Then, steroid therapy was withdrawn within one week. Tacrolimus and mycophenolate treatment were started 3 days before transplantation with tacrolimus target levels of 4 to 8 ng/mL. In the absence of rejection, tacrolimus was withdrawn between 3 and 12 months post-transplant to reach mycophenolate mofetil monotherapy of 2 g/day or equivalent. Results Six patients were treated with the above protocol. At last follow-up, graft and patient survival were 100%. MDRD glomerular filtration rates were 54, 60, and 62 mL/min at 3 months, 12 months and last follow-up, respectively. None of the patients developed PRA post-transplant. One episode of acute rejection Banff IA occurred 9 years after transplantation due to non-adherence with good outcome after treatment. The mean number of concomitant drugs given with mycophenolate was 2.6. Four patients needed antihypertensive drugs. Conclusion Steroid-free de novo treatment and calcineurin-inhibitor weaning with mycophenolate monotherapy is feasible in first HLA-identical kidney transplantation from a living sibling. Although recipients of a first HLA-identical living-donor kidney transplant seem to need less immunosuppression, there are no guideline recommendations for these patients, and few prospective trials are available. PMID:24491040

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

    PubMed Central

    2011-01-01

    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 understand molecular basis of

  10. Refractory linear IgA bullous dermatosis successfully treated with mycophenolate sodium.

    PubMed

    Marzano, Angelo V; Ramoni, Stefano; Spinelli, Diana; Alessi, Elvio; Berti, Emilio

    2008-01-01

    Linear IgA bullous dermatosis (LABD) is a rare, blistering autoimmune disease characterized by linear deposits of IgA at the basement membrane zone (BMZ), with the possible presence of circulating IgA anti-BMZ antibodies. LABD of childhood is usually self-healing, while in adults it follows a more prolonged course and refractory cases may rarely occur. The first-line treatment for LABD is dapsone in monotherapy or in combination with systemic corticosteroids, but various therapeutic approaches have been used in non-responder patients. We report two adult patients with refractory LABD successfully treated with enteric-coated mycophenolate sodium (EC-MPS), a recently introduced formulation of mycophenolic acid (MPA). MPA is an immunosuppressive agent that acts by inhibiting monophosphate dehydrogenase, a key enzyme in the novo synthesis of purines. Based on the present cases, we indicate EC-MPS as being a safe and effective adjuvant therapy in the treatment of LABD when dapsone or the other steroid-sparing drugs fail. It seems to offer an improved gastric side effect profile in comparison with the classic formulation of MPA, namely its ester mycophenolate mofetil (MMF).

  11. Treatment of Idiopathic Membranous Nephropathy

    PubMed Central

    Austin, Howard A.

    2012-01-01

    Exciting progress recently has been made in our understanding of idiopathic membranous nephropathy, as well as treatment of this disease. Here, we review important advances regarding the pathogenesis of membranous nephropathy. We will also review the current approach to treatment and its limitations and will highlight new therapies that are currently being explored for this disease including Rituximab, mycophenolate mofetil, and adrenocorticotropic hormone, with an emphasis on results of the most recent clinical trials. PMID:22859855

  12. Mycophenolic Acid Inhibits Migration and Invasion of Gastric Cancer Cells via Multiple Molecular Pathways

    PubMed Central

    Dun, Boying; Sharma, Ashok; Teng, Yong; Liu, Haitao; Purohit, Sharad; Xu, Heng; Zeng, Lingwen; She, Jin-Xiong

    2013-01-01

    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. PMID:24260584

  13. Enteric coating of mycophenolate reduces dosage adjustments.

    PubMed

    Brister, K; Yau, C L; Slakey, D

    2009-06-01

    Mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS) are bioequivalent. However, the effectiveness of MMF may be limited by gastrointestinal (GI) side effects. This study assessed the relationship between the number of medication dosage adjustments and posttransplantation side effects. In a review of 109 kidney transplant patients, 65 initially received MMF and 44 initially received EC-MPS. The incidences of patient-reported GI complications were significantly different: MMF 45.5% vs EC-MPS 35.3% (P = .0194). The proportions of patients requiring dosage adjustment due to GI complications were MMF 5.9% and EC-MPS 2.3% (P < .0001). Patients receiving MMF were more likely to experience GI complications resulting in dosage adjustment (odds ratio = 9.9; P = .0306). The incidences of acute rejection, cytomegalovirus (CMV), and leukopenia resulting in dosage adjustment were not significantly different. Patients receiving MMF required more immunosuppressive medication adjustments, which may complicate care and decrease overall compliance.

  14. In Vitro Influence of Mycophenolic Acid on Selected Parameters of Stimulated Peripheral Canine Lymphocytes

    PubMed Central

    Guzera, Maciej; Szulc-Dąbrowska, Lidia; Cywińska, Anna; Archer, Joy; Winnicka, Anna

    2016-01-01

    Mycophenolic acid (MPA) is an active metabolite of mycophenolate mofetil, a new immunosuppressive drug effective in the treatment of canine autoimmune diseases. The impact of MPA on immunity is ambiguous and its influence on the canine immune system is unknown. The aim of the study was to determine markers of changes in stimulated peripheral canine lymphocytes after treatment with MPA in vitro. Twenty nine healthy dogs were studied. Phenotypic and functional analysis of lymphocytes was performed on peripheral blood mononuclear cells cultured with mitogens and different MPA concentrations– 1 μM (10−3 mol/m3), 10 μM or 100 μM. Apoptotic cells were detected by Annexin V and 7-aminoactinomycin D (7-AAD). The expression of antigens (CD3, CD4, CD8, CD21, CD25, forkhead box P3 [FoxP3] and proliferating cell nuclear antigen [PCNA]) was assessed with monoclonal antibodies. The proliferation indices were analyzed in carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled cells. All analyses were performed using flow cytometry. The influence of MPA on apoptosis was dependent on the mechanism of cell activation and MPA concentration. MPA caused a decrease in the expression of lymphocyte surface antigens, CD3, CD8 and CD25. Its impact on the expression of CD4 and CD21 was negligible. Its negative influence on the expression of FoxP3 was dependent on cell stimulation. MPA inhibited lymphocyte proliferation. In conclusion, MPA inhibited the activity of stimulated canine lymphocytes by blocking lymphocyte activation and proliferation. The influence of MPA on the development of immune tolerance–expansion of Treg cells and lymphocyte apoptosis–was ambiguous and was dependent on the mechanism of cellular activation. The concentration that MPA reaches in the blood may lead to inhibition of the functions of the canine immune system. The applied panel of markers can be used for evaluation of the effects of immunosuppressive compounds in the dog. PMID:27138877

  15. Our experience with wet-wrap treatment.

    PubMed

    Albarrán-Planelles, C; Jiménez-Gallo, D; Linares-Barrios, M; Martínez-Rodríguez, A

    2014-04-01

    A wide range of treatments are currently available for severe atopic dermatitis, including systemic therapies such as ciclosporin, corticosteroids, azathioprine, methotrexate, mofetil mycophenolate, and omalizumab. In patients who can no longer take systemic drugs or who need a dose reduction, wet-wrap treatment can be an excellent option. To date, wet wraps have mostly been used in severe cases of childhood atopic dermatitis. We report our experience with wet-wrap treatment in 5 adults with atopic dermatitis and 2 with nodular prurigo. The results were satisfactory and there were few adverse effects.

  16. Treatment-refractory multi-lineage autoimmune cytopenia after unrelated cord blood transplantation: remission after combined bortezomib and vincristine treatment.

    PubMed

    Waespe, Nicolas; Zeilhofer, Ulrike; Güngör, Tayfun

    2014-11-01

    Autoimmune cytopenias (AC) after allogeneic hematopoietic stem cell transplantation (HSCT) are associated with a dismal prognosis. We describe a 1-year-old female with multi-lineage AC occurring on day +43 after HSCT. Multi-agent treatment with high-dose prednisolone, intravenous immunoglobulins, cyclosporine A, mycophenolate mofetil, sirolimus, and rituximab was unsuccessful. Combined treatment with bortezomib and vincristine in addition to ongoing immunosuppressive therapy was started on day +414 with transfusion-independence after day +444. Immunosuppressants were tapered until day +638. On day +1,121 the patient remained in remission. Bortezomib with vincristine may be a promising treatment modality for refractory AC after HSCT that requires further study.

  17. Treatment of pure red-cell aplasia with cyclosporine in a renal transplant patient.

    PubMed

    Yildirim, Rahsan; Bilen, Yusuf; Keles, Mustafa; Uyanik, Abdullah; Gokbulut, Puren; Aydinli, Bulent

    2013-02-01

    Acquired pure red-cell aplasia is a rare disorder that can be either idiopathic or associated with certain autoimmune diseases, pregnancy, lymphoproliferative disorders, nutritional deficiencies, or medicines. We present a deceased-donor renal transplant patient who developed pure red-cell aplasia associated with mycophenolate mofetil or tacrolimus and was treated with cyclosporine. A 20-year-old woman was transplanted from a deceased donor 1 month earlier and presented to us with symptoms of fatigue, prostration, and palpitation. The results of a laboratory examination revealed anemia. A diagnostic work-up resulted in a diagnosis of pure red-cell aplasia. Mycophenolate mofetil was discontinued. Tacrolimus also was replaced with cyclosporine 2 months after mycophenolate mofetil was halted because of a lack of improvement in anemia. Three months later, her anemia improved with cyclosporine. Starting cyclosporine instead of tacrolimus or mycophenolate mofetil showed good improvement in our patient within 6 months of therapy.

  18. Adoptive Immunotherapy Combined with Hematopoietic Cell Transplantation as a Therapeutic Treatment of Prostate Cancer

    DTIC Science & Technology

    2009-07-01

    irradiation (TBI) followed by postgrafting immunosuppression with mycophenolate mofetil ( MMF ) and cyclosporin A (CSP) for 28 and 35 days respectively...immunosuppression of MMF and CSP (11). We now believe this problem was due to our replacing an aged 4 meV linear accelerator (Linac) with a newer 6 meV...lymphocyte reaction MMF mycophenolate mofetil PBL peripheral blood lymphocytes PBMC peripheral blood mononuclear cells PBS phosphate buffered

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

    PubMed

    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.

  20. Primary CNS lymphoproliferative disease, mycophenolate and calcineurin inhibitor usage

    PubMed Central

    Crane, Genevieve M.; Powell, Helen; Kostadinov, Rumen; Rocafort, Patrick Tim; Rifkin, Dena E.; Burger, Peter C.; Ambinder, Richard F.; Swinnen, Lode J.; Borowitz, Michael J.; Duffield, Amy S.

    2015-01-01

    Immunosuppression for solid organ transplantation increases lymphoproliferative disease risk. While central nervous system (CNS) involvement is more rare, we noticed an increase in primary CNS (PCNS) disease. To investigate a potential association with the immunosuppressive regimen we identified all post-transplant lymphoproliferative disease (PTLD) cases diagnosed over a 28-year period at our institution (174 total, 29 PCNS) and all similar cases recorded in a United Network for Organ Sharing-Organ Procurement and Transplant Network (UNOS-OPTN) data file. While no PCNS cases were diagnosed at our institution between 1986 and 1997, they comprised 37% of PTLD cases diagnosed from 2011–2014. PCNS disease was more often associated with renal vs. other organ transplant, Epstein-Barr virus, large B-cell morphology and mycophenolate mofetil (MMF) as compared to PTLD that did not involve the CNS. Calcineurin inhibitors were protective against PCNS disease when given alone or in combination with MMF. A multivariate analysis of a larger UNOS-OPTN dataset confirmed these findings, where both MMF and lack of calcineurin inhibitor usage were independently associated with risk for development of PCNS PTLD. These findings have significant implications for the transplant community, particularly given the introduction of new regimens lacking calcineurin inhibitors. Further investigation into these associations is warranted. PMID:26460822

  1. Pharmacokinetic Assessment of Drug‐Drug Interactions of Isavuconazole With the Immunosuppressants Cyclosporine, Mycophenolic Acid, Prednisolone, Sirolimus, and Tacrolimus in Healthy Adults

    PubMed Central

    Groll, Andreas H.; Desai, Amit; Han, David; Howieson, Corrie; Kato, Kota; Akhtar, Shahzad; Kowalski, Donna; Lademacher, Christopher; Lewis, William; Pearlman, Helene; Mandarino, Debra; Yamazaki, Takao

    2016-01-01

    Abstract This report summarizes phase 1 studies that evaluated pharmacokinetic interactions between the novel triazole antifungal agent isavuconazole and the immunosuppressants cyclosporine, mycophenolic acid, prednisolone, sirolimus, and tacrolimus in healthy adults. Healthy subjects received single oral doses of cyclosporine (300 mg; n = 24), mycophenolate mofetil (1000 mg; n = 24), prednisone (20 mg; n = 21), sirolimus (2 mg; n = 22), and tacrolimus (5 mg; n = 24) in the presence and absence of clinical doses of oral isavuconazole (200 mg 3 times daily for 2 days; 200 mg once daily thereafter). Coadministration with isavuconazole increased the area under the concentration‐time curves (AUC0–∞) of tacrolimus, sirolimus, and cyclosporine by 125%, 84%, and 29%, respectively, and the AUCs of mycophenolic acid and prednisolone by 35% and 8%, respectively. Maximum concentrations (Cmax) of tacrolimus, sirolimus, and cyclosporine were 42%, 65%, and 6% higher, respectively; Cmax of mycophenolic acid and prednisolone were 11% and 4% lower, respectively. Isavuconazole pharmacokinetics were mostly unaffected by the immunosuppressants. Two subjects experienced elevated creatinine levels in the cyclosporine study; most adverse events were not considered to be of clinical concern. These results indicate that isavuconazole is an inhibitor of cyclosporine, mycophenolic acid, sirolimus, and tacrolimus metabolism. PMID:27273343

  2. Pemphigus vulgaris: approach to treatment.

    PubMed

    Sinha, Animesh A; Hoffman, Melissa B; Janicke, Elise C

    2015-04-01

    The therapeutic management of pemphigus vulgaris (PV) is centered around immunosuppression, which can be generalized, as in the use of corticosteroids or steroid sparing agents, or specific, as in therapeutic blockage of autoantibody production, certain cytokines, or signaling pathways. Currently, the backbone of treatment for PV, particularly, first line therapy, remains systemic corticosteroids. Although very effective, the significant side effects of long-term corticosteroid usage are well documented. Adjunctive therapies aim to eliminate, or at least decrease, the necessary dose of corticosteroids. Specifically, azathioprine, cyclophosphamide, methotrexate, cyclosporine, mycophenolate mofetil and dapsone are now widely used in PV. Intravenous immunoglobulin (IVIG), plasmapheresis, immunoadsorption, and most recently, rituximab, are other members of the therapeutic armamentarium. However, despite the widening range of treatment options in PV, well-controlled clinical trials and consensus guidelines are lacking.

  3. Mycophenolate

    MedlinePlus

    ... Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for ...

  4. Nonrelapse mortality and mycophenolic acid exposure in nonmyeloablative hematopoietic cell transplantation.

    PubMed

    McDermott, Cara L; Sandmaier, Brenda M; Storer, Barry; Li, Hong; Mager, Donald E; Boeckh, Michael J; Bemer, Meagan J; Knutson, Jennifer; McCune, Jeannine S

    2013-08-01

    We evaluated the pharmacodynamic relationships between mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), and outcomes in 308 patients after nonmyeloablative hematopoietic cell transplantation. Patients were conditioned with total body irradiation ± fludarabine, received grafts from HLA-matched related (n = 132) or unrelated (n = 176) donors, and received postgrafting immunosuppression with MMF and a calcineurin inhibitor. Total and unbound MPA pharmacokinetics were determined to day 25; maximum a posteriori Bayesian estimators were used to estimate total MPA concentration at steady state (Css). Rejection occurred in 9 patients, 8 of whom had a total MPA Css less than 3 μg/mL. In patients receiving a related donor graft, MPA Css was not associated with clinical outcomes. In patients receiving an unrelated donor graft, low total MPA Css was associated with increased grades III to IV acute graft-versus-host disease and increased nonrelapse mortality but not with day 28 T cell chimerism, disease relapse, cytomegalovirus reactivation, or overall survival. We conclude that higher initial oral MMF doses and subsequent targeting of total MPA Css to greater than 2.96 μg/mL could lower grades III to IV acute graft-versus-host disease and nonrelapse mortality in patients receiving an unrelated donor graft.

  5. Non-relapse mortality and mycophenolic acid exposure in nonmyeloablative hematopoietic cell transplantation

    PubMed Central

    McDermott, Cara L.; Sandmaier, Brenda M.; Storer, Barry; Li, Hong; Mager, Donald E.; Boeckh, Michael J.; Bemer, Meagan J.; Knutson, Jennifer; McCune, Jeannine S.

    2013-01-01

    We evaluated the pharmacodynamic relationships between mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), and outcomes in 308 patients after nonmyeloablative hematopoietic cell transplant. Patients were conditioned with total body irradiation ± fludarabine, received grafts from HLA-matched related (N=132) or unrelated (N=176) donors, and received post-grafting immunosuppression with MMF and a calcineurin inhibitor. Total and unbound MPA pharmacokinetics were determined to day 25; maximum a posteriori Bayesian estimators were used to estimate total MPA concentration at steady state (Css). Rejection occurred in nine patients, eight of whom had a total MPA Css less than 3 μg/mL. In patients receiving a related donor graft, MPA Css was not associated with clinical outcomes. In patients receiving an unrelated donor graft, low total MPA Css was associated with increased grades 3–4 acute graft versus host disease (aGVHD) and increased non-relapse mortality, but not with day 28 T-cell chimerism, disease relapse, cytomegalovirus reactivation, or overall survival. We conclude that higher initial oral MMF doses and subsequent targeting of total MPA Css to greater than 2.96 μg/mL could lower grades 3–4 aGVHD and non-relapse mortality in patients receiving an unrelated donor graft. PMID:23660171

  6. Systemic treatment of severe atopic eczema: a systematic review.

    PubMed

    Schmitt, Jochen; Schäkel, Knut; Schmitt, Natalie; Meurer, Michael

    2007-01-01

    Systemic immunosuppressive agents are recommended for patients with atopic eczema in whom disease activity cannot be controlled adequately with topical treatments. Guidelines do not give clear advice which agents to prefer. We systematically reviewed clinical trials on systemic treatment for severe atopic eczema to provide evidence-based treatment recommendations. Standardized literature search, independent standardized assessment of eligibility and data abstraction was performed by 2 reviewers. Twenty-seven studies totalling 979 patients were included. Eleven studies consistently showed effectiveness of cyclosporine. Cyclosporine is recommended as first option for patients with atopic eczema refractory to conventional treatment. Evidence from randomized controlled trials also exists for interferon-? and azathioprine. Although frequently used in clinical practice, systemic glucocorticosteroids have not been assessed adequately in studies. Mycophenolate mofetile showed effectiveness in 2 small uncontrolled studies. Intravenous immunoglobulins and infliximab are not recommended based on published data.

  7. Intra-individual variability of mycophenolic acid concentration according to renal function in liver transplant recipients receiving mycophenolate monotherapy

    PubMed Central

    Song, Gi-Won; Jung, Dong-Hwan; Park, Gil-Chun; Ahn, Chul-Soo; Moon, Deok-Bog; Ha, Tae-Yong; Kim, Ki-Hun; Lee, Sung-Gyu

    2017-01-01

    Backgrounds/Aims Mycophenolate mofetil (MMF) has wide inter- and intra-individual variability of mycophenolic acid (MPA) after liver transplantation (LT). On this study, we aimed to analyse the intra-individual variability of MPA concentration in stable adult LT recipients receiving MMF monotherapy and develop a method to determine the target level in the situation of wide intra-individual variability. Methods This retrospective cross-sectional study included 30 LT recipients. All patients received MMF monotherapy at a dose of 500 mg twice daily for ≥2 years and were divided into two groups based on renal function. MPA concentration-associated values were presented as mean with standard deviation and coefficient of variation (CV). Results The normal renal function group (n=15) showed a mean 12-hour MPA concentration of 2.5±0.5 µg/ml (range, 1.8±0.5 to 3.6±0.7 µg/ml) and a mean CV of 20.4±7.7% (range, 8.7% to 39.4%). In the renal dysfunction group (n=15), the 12-hour MPA concentration fluctuated more widely with a mean value of 3.7±0.9 µg/ml (range, 2.8±0.8 to 5.1±1.2 µg/ml) and a mean CV of 24.5±4.9% (range, 17.1% to 37.5%). The 12-hour MPA concentration was significantly higher in the renal dysfunction group, as compared to the normal renal function group (p=0.001); whereas, the CV was not significantly different between the two groups (p=0.093). Conclusions We determined the inter- and intra-individual variability of 12-hour MPA concentration after LT. The results suggested that therapeutic drug monitoring of MPA is necessary due to the inter-individual and intra-individual variability of MMF pharmacokinetics, especially in LT recipients with renal dysfunction. PMID:28317040

  8. RECENT CLINICAL TRIALS IN LUPUS NEPHRITIS

    PubMed Central

    Ward, Michael M.

    2014-01-01

    SYNOPSIS Recent clinical trials have provided evidence for the efficacy of low-dose intravenous cyclophosphamide and mycophenolate mofetil as induction treatment for patients with proliferative lupus nephritis in comparative trials with standard-dose intravenous cyclophosphamide. Trials of maintenance treatments have had more variable results, but suggest that mycophenolate mofetil may be similar to quarterly standard-dose intravenous cyclophosphamide and somewhat more efficacious than azathioprine. Differential responses to mycophenolate mofetil based on ethnicity suggest that it may be more effective in black and Hispanic patients. Rituximab was not efficacious as an adjunct to induction treatment with mycophenolate mofetil. PMID:25034160

  9. Successful treatment of severe myasthenia gravis developed after allogeneic hematopoietic stem cell transplantation with plasma exchange and rituximab.

    PubMed

    Unal, Sule; Sag, Erdal; Kuskonmaz, Baris; Kesici, Selman; Bayrakci, Benan; Ayvaz, Deniz C; Tezcan, Ilhan; Yalnızoglu, Dilek; Uckan, Duygu

    2014-05-01

    Myasthenia gravis is among the rare complications after allogeneic hematopoietic stem cell transplantation and is usually associated with chronic GVHD. Herein, we report a 2-year and 10 months of age female with Griscelli syndrome, who developed severe myasthenia gravis at post-transplant +22nd month and required respiratory support with mechanical ventilation. She was unresponsive to cyclosporine A, methylprednisolone, intravenous immunoglobulin, and mycophenolate mofetil and the symptoms could only be controlled after plasma exchange and subsequent use of rituximab, in addition to cyclosporine A and mycophenolate mofetil maintenance. She is currently asymptomatic on the 6th month of follow-up.

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

    PubMed

    Desai, Jay; Ramos-Platt, Leigh; Mitchell, Wendy G

    2015-01-01

    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.

  11. Uveitis: advances in understanding of pathogenesis and treatment.

    PubMed

    Read, Russell W

    2006-08-01

    Uveitis is a leading cause of blindness affecting individuals of all ages, genders, and races. Uveitis may be due to autoimmune, infectious, toxic, malignant, or traumatic processes. Some evidence supports an association between conditions previously presumed to be autoimmune and viral infectious agents. For autoimmune uveitis, therapy is nonspecific, typically beginning with corticosteroids. For nonresponsive disease or for corticosteroid sparing, recent reports on mycophenolate mofetil, infliximab, and interferon therapy show success for various forms of uveitis. Treatment of the complications of uveitis, especially cystoid macular edema, is difficult. Vitamin E appears to offer little benefit, whereas octreotide may be effective. Recent collaborative efforts at standardization in the field should enhance studies on these conditions.

  12. Hyperkalemic distal renal tubular acidosis caused by immunosuppressant treatment with tacrolimus in a liver transplant patient: case report.

    PubMed

    Riveiro-Barciela, M; Campos-Varela, I; Tovar, J L; Vargas, V; Simón-Talero, M; Ventura-Cots, M; Crespo, M; Bilbao, I; Castells, L

    2011-12-01

    Nephrotoxicity is one of the most common side effects of long-term immunosuppressive therapy with calcineurin inhibitors. We describe a case of distal renal tubular acidosis secondary to tacrolimus administration. A 43-year-old man with end-stage liver disease due to hepatitis C and B virus infections and alcoholic cirrhosis received a liver transplantation under immunosuppressive treatment with tacrolimus and mycophenolate mofetil. In the postoperative period, the patient developed hyperkalemic hyperchloremic metabolic acidosis, with a normal serum anion gap and a positive urinary anion gap, suggesting distal renal tubular acidosis. We excluded other causes of hyperkalemia. Administration of intravenous bicarbonate, loop diuretics, and oral resin exchanger corrected the acidosis and potassium levels. Distal renal tubular acidosis is one of several types of nephrotoxicity induced by tacrolimus treatment, resulting from inhibition of potassium secretion in the collecting duct. Treatment to correct the acidosis and hyperkalemia should be promptly initiated, and the tacrolimus dose adjusted when possible.

  13. Lupus nephritis: induction therapy in severe lupus nephritis--should MMF be considered the drug of choice?

    PubMed

    Rovin, Brad H; Parikh, Samir V; Hebert, Lee A; Chan, Tak Mao; Mok, Chi Chiu; Ginzler, Ellen M; Hooi, Lai Seong; Brunetta, Paul; Maciuca, Romeo; Solomons, Neil

    2013-01-01

    Severe lupus nephritis is an aggressive disease that requires an aggressive approach to treatment. Recent randomized clinical trials showed that mycophenolate mofetil compared favorably with cyclophosphamide (traditional approach) for remission induction. Consequently, mycophenolate mofetil is now commonly recommended as first-line therapy. Nevertheless, the role of mycophenolate mofetil in treating severe lupus nephritis is unclear, because such patients were excluded from these trials. With this limitation as background, this work addresses the question of mycophenolate mofetil for induction therapy for severe lupus nephritis. We performed a systematic review of the outcomes of treating severe lupus nephritis with mycophenolate mofetil or cyclophosphamide. Because no studies directly addressed this question, these data were extracted from the published literature or obtained by personal communications from investigators. There is no universally accepted definition, and therefore, severe lupus nephritis was arbitrarily defined by renal histology, resistance to therapy, or level of kidney function at presentation. For each trial analyzed, we determined the partial and complete remission rates. Long-term outcomes were compared when available. The pooled results suggest that mycophenolate mofetil and cyclophosphamide are equally effective in inducing remission of severe lupus nephritis. However, relapse rates and risk of developing ESRD were higher for mycophenolate mofetil compared with cyclophosphamide. In conclusion, in the short term, mycophenolate mofetil and cyclophosphamide are about equal in inducing remission. However, long-term outcomes suggest better preservation of kidney function and fewer relapses with cyclophosphamide therapy. Therefore, mycophenolate mofetil should not yet be considered the induction drug of choice for severe lupus nephritis.

  14. Is mycophenolate more than just an immunosuppressant?--An overview.

    PubMed

    Iyer, Abishek; Brown, Lindsay

    2009-02-01

    The development of immunosuppressant compounds, such as cyclosporine and tacrolimus was crucial to the success of transplant surgery and for treatment of autoimmune diseases. However, immunosuppressant therapy may increase the concentrations of reactive oxygen species (ROS), inducing oxidative damage such as an increased vascular damage. The major source of ROS in the vascular endothelial cells is NADPH oxidase. The subunit structure and function of this enzyme complex in vascular cells differs from that in phagocytic leucocytes. The enzyme subunits Nox1, Nox2 and Nox4 are only found in vascular cells. The GTP-dependent protein subunit Rac 1 needs to be activated for this enzyme to function. Inhibiting this protein subunit should reduce NADPH oxidase-induced oxidative stress. In the cardiovascular system, oxidative stress is observed as hypertension, hypertrophy, fibrosis, conduction abnormalities and endothelial dysfunction, as well as cardiac allograft vasculopathy in transplant patients. In contrast to cyclosporine and tacrolimus, the immunosuppressant mycophenolate inhibits the Rac 1 subunit thus inhibiting NADPH oxidase in the vasculature. This may reduce oxidative stress, prevent the development of cardiac allograft vasculopathy, decrease the deterioration of vascular function and improve cardiovascular function chronically in transplant patients. This overview discusses whether this antioxidant immunosuppressive property could translate into a more general protective role for mycophenolate in the prevention of cardiovascular disease.

  15. Cyclosporine Sparing Effect of Enteric-Coated Mycophenolate Sodium in De Novo Kidney Transplantation

    PubMed Central

    Lee, Su Hyung; Oh, Chang-Kwon; Kim, Myoung Soo; Kim, Sung Joo; Ha, Jongwon

    2017-01-01

    Purpose The increased tolerability of enteric-coated mycophenolate sodium (EC-MPS), compared to mycophenolate mofetil, among kidney transplant recipients has the potential to facilitate cyclosporine (CsA) minimization. Therefore, a prospective trial to determine the optimum EC-MPS dose in CsA-based immunosuppression regimens is necessary. Materials and Methods A comparative, parallel, randomized, open-label study was performed for 140 patients from four centers to compare the efficacy and tolerability of low dose CsA with standard dose EC-MPS (the investigational group) versus standard dose CsA with low dose EC-MPS (the control group) for six months in de novo kidney transplant recipients. Graft function, the incidence of efficacy failure [biopsy-confirmed acute rejection (BCAR), death, graft loss, loss to follow-up], and adverse events were compared. Results The mean estimated glomerular filtration rate (eGFR) of the investigational group at six months post-transplantation was non-inferior to that of the control group (confidence interval between 57.3 mL/min/1.73m2 and 67.4 mL/min/1.73 m2, p<0.001). One graft loss was reported in the control group, and no patient deaths were reported in either group. The incidence of BCAR of the investigational group was 8.7%, compared to 18.8% in the control group (p=0.137), during the study period. There were no significant differences (p>0.05) in the incidence of discontinuations and serious adverse events (SAE) between the groups. Conclusion CsA minimization using a standard dose of EC-MPS kept the incidence of acute rejection and additional risks as low as conventional immunosuppression and provided therapeutic equivalence in terms of renal graft function and safety issues. PMID:27873516

  16. A Protocol for the Pharmacokinetics of Enteric Coated Mycophenolate Sodium in Lupus Nephritis (POEMSLUN): an open-label, randomised controlled trial

    PubMed Central

    Ranganathan, Dwarakanathan; John, George T; Healy, Helen; Roberts, Matthew J; Fassett, Robert G; Lipman, Jeffrey; Kubler, Paul; Ungerer, Jacobus; McWhinney, Brett C; Lim, Aaron; Purvey, Megan; Reyaldeen, Reza; Roberts, Jason A

    2013-01-01

    Introduction Mycophenolate sodium, an enteric-coated tablet (EC-MPS), is as effective and safe as mycophenolate mofetil (MMF) in preventing transplant rejection. EC-MPS and MMF improve the outcome of severe lupus nephritis (LN) and have fewer side effects than pulsed intravenous cyclophosphamide. Blood concentrations of mycophenolic acid (MPA), the active metabolite of EC-MPS, vary between participants despite fixed dosing. Interpatient variability has been studied in transplantation, but not well documented in LN. The relationship between MPA concentration and its clinical effect on LN has not been described. Methods and analysis This is a prospective, open-label, randomised controlled trial. –32 participants with LN who meet the inclusion and exclusion criteria will be randomised into two groups: one receiving a fixed dose of EC-MPS and the second, a dosing regimen that is titrated with therapeutic drug monitoring. Included participants will have blood sampled over a period of 8–12 h on three different occasions. Pharmacokinetic parameters will be calculated using non-compartmental methods. Ethics and dissemination The Human Research and Ethics Committee of the Royal Brisbane Women's Hospital have approved this study. The study is registered with Australian and New Zealand Clinical Trials Registry—ACTRN12611000798965 We planned to present the de-identified information at conferences and publish the results in medical journals. Trial Registration ACTRN12611000798965 PMID:23929919

  17. A limited sampling schedule to estimate mycophenolic Acid area under the concentration-time curve in hematopoietic cell transplantation recipients.

    PubMed

    Li, Hong; Mager, Donald E; Bemer, Meagan J; Salinger, David H; Vicini, Paolo; Sandmaier, Brenda M; Nash, Richard; McCune, Jeannine S

    2012-11-01

    Mycophenolate mofetil (MMF) is a key component of postgrafting immunosuppression in hematopoietic cell transplant (HCT) recipients. The plasma area under the curve (AUC) of its active metabolite, mycophenolic acid (MPA), is associated with MMF efficacy and toxicity. This study developed a population pharmacokinetic model of MPA in HCT recipients and created limited sampling schedules (LSSs) to enable individualized pharmacotherapy. A retrospective evaluation of MPA concentration-time data following a 2-hour MMF intravenous (IV) infusion was conducted in 77 HCT recipients. The final model consisted of 1 and 2 compartments for MMF and MPA pharmacokinetics, respectively. The mean estimated values (coefficient of variation, %) for total systemic clearance, distributional clearance, and central and peripheral compartment volumes of MPA were 36.9 L/h (34.5%), 15.3 L/h (80.4%), 11.9 L (71.7%), and 182 L (127%), respectively. No covariates significantly explained variability among individuals. Optimal LSSs were derived using a simulation approach based on the scaled mean squared error. A 5-sample schedule of 2, 2.5, 3, 5, and 6 hours from the start of the infusion precisely estimated MPA AUC(0-12 h) for Q12-hour IV MMF. A comparable schedule (2, 2.5, 3, 4, and 6 hours) similarly estimated MPA AUC(0-8) (h) for Q8-hour dosing.

  18. A Limited Sampling Schedule to Estimate Mycophenolic Acid Area Under the Concentration-Time Curve in Hematopoietic Cell Transplantation Recipients

    PubMed Central

    Li, Hong; Mager, Donald E.; Bemer, Meagan J.; Salinger, David H.; Vicini, Paolo; Sandmaier, Brenda M.; Nash, Richard; McCune, Jeannine S.

    2011-01-01

    Mycophenolate mofetil (MMF) is a key component of post-grafting immunosuppression in hematopoietic cell transplant (HCT) recipients. The plasma area under the curve (AUC) of its active metabolite, mycophenolic acid (MPA), is associated with MMF efficacy and toxicity. This study developed a population pharmacokinetic model of MPA in HCT recipients and created limited sampling schedules (LSS) to enable individualized pharmacotherapy. A retrospective evaluation of MPA concentration-time data following a 2 hr MMF intravenous (IV) infusion was conducted in 77 HCT recipients. The final model consisted of one and two compartments for MMF and MPA pharmacokinetics, respectively. The mean estimated values (coefficient of variation, %) for total systemic clearance, distributional clearance, and central and peripheral compartment volumes of MPA were 36.9 L/h (34.5%), 15.3 L/h (80.4%), 11.9 L (71.7%), and 182 L (127%), respectively. No covariates significantly explained variability among individuals. Optimal LSS were derived using a simulation approach based on the scaled mean squared error. A five-sample schedule of 2, 2.5, 3, 5, and 6 hr from the start of the infusion precisely estimated MPA AUC0–12 hr for Q12 hr IV MMF. A comparable schedule (2, 2.5, 3, 4 and 6 hr) similarly estimated MPA AUC0–8hr for Q8 hr dosing. PMID:22174435

  19. Sjögren Sensory Neuronopathy (Sjögren Ganglionopathy): Long-Term Outcome and Treatment Response in a Series of 13 Cases.

    PubMed

    Pereira, P Ricardo; Viala, Karine; Maisonobe, Thierry; Haroche, Julien; Mathian, Alexis; Hié, Miguel; Amoura, Zahir; Cohen Aubart, Fleur

    2016-05-01

    Primary Sjögren syndrome (SS) is an autoimmune disease mainly affecting the exocrine glands causing a sicca syndrome. Neurological manifestations are rarely seen in SS although they are debilitating. Peripheral neuropathies namely sensory axonal neuropathy and painful small fiber neuropathy are the most frequent neurological manifestations. Sensory neuronopathy (SN) is less frequently seen although leading to more severe handicap.The aim of the study was to analyze the clinical presentation and treatment efficacy in a series of SS-related SN.We retrospectively studied patients with SS fulfilling the American-European Classification Criteria and SN according to recent criteria. Studied variables were neurological findings, associated autoimmune diseases, biological profiles, nerve conduction and sensory/motor amplitudes study, treatments received, and outcomes. Handicap scores were studied at beginning and end of each treatment using the modified Rankin Scale (mRS).Thirteen patients were included (12 women, 1 man; median age 55 years at SN diagnosis) presenting with SN with a median follow-up of 3 years (range 2-17). In 11 patients, SN preceded or coincided with SS diagnosis. Most common neurological findings were ataxia and areflexia followed by paresthesia and pain. Lower limbs were more affected than upper limbs, neurological deficits were often symmetric and cranial nerves were affected in 3 patients. Seven patients were treated with corticosteroids, 7 with mycophenolate mofetil, 6 with hydroxychloroquine, 5 with intravenous immunoglobulins, 4 with cyclophosphamide, and 2 patients received other immunosuppressive drugs. At the beginning and at the end of follow-up, average mRS was 2.15 (median 2) and 2.38 (median 2), respectively.SS-related SN progression is heterogeneous but tends to be chronic, insidious, and debilitating despite treatment. From these data concerning a small number of patients, treatment strategies with corticosteroids in association with

  20. Production of mycophenolic acid by Penicillium roqueforti strains.

    PubMed Central

    Lafont, P; Debeaupuis, J P; Gaillardin, M; Payen, J

    1979-01-01

    Sixteen strains of Penicillium roqueforti Thom, isolated from blue-molded cheeses, were studied. In vitro, all of these strains produced mycophenolic acid, some on the order of 0.8 to 4 mg/g od dry culture. The greatest yields were obtained after 10 days of incubation of cultures at 15 degrees C. However, under some experimental conditions, mycophenolic acid was not alone responsible for the toxicity of culture extracts to chicken embryos. PMID:453818

  1. Influence of lansoprazole and rabeprazole on mycophenolic acid pharmacokinetics one year after renal transplantation.

    PubMed

    Miura, Masatomo; Satoh, Shigeru; Inoue, Kazuyuki; Kagaya, Hideaki; Saito, Mitsuru; Suzuki, Toshio; Habuchi, Tomonori

    2008-02-01

    Peptic ulcer disease is a common complication after organ transplantation, and long-term administration of antiulcer agents is needed in many renal transplant recipients. Although several drug interactions with mycophenolic acid (MPA), the active metabolite of the prodrug mycophenolate mofetil (MMF), have been reported, little is known about the interaction between MPA and proton pump inhibitors (PPIs). The present study investigated the drug interaction between MMF and lansoprazole or rabeprazole and the impact of cytochrome (CYP) 2C19, and multidrug resistance (MDR)1 C3435T polymorphisms on these drug interactions at 1 year after renal transplantation. Retrospectively, 61 recipients were divided into 3 groups: MMF and tacrolimus as combination immunosuppressive therapy, together with either 30 mg lansoprazole (n = 22) or 10 mg rabeprazole (n = 17), or without PPI (n = 22). One year after transplantation, plasma concentrations of MPA were measured by high-performance liquid chromatography. The mean dose-unadjusted and -adjusted Cmax of MPA with 30 mg lansoprazole were significantly lower than those without PPI (11.8 vs. 17.8 microg/mL, P = 0.0197, and 22.6 vs. 33.1 ng/mL/mg MMF, P = 0.0222, respectively). In recipients having the CYP2C19 *1/*2+*1/*3 or MDR1 C3435T CC genotype, the mean dose-adjusted AUC0-12 of MPA with 30 mg lansoprazole was significantly smaller than that with 10 mg rabeprazole or without PPI. The plasma concentration of MPA was influenced by 30 mg lansoprazole but not 10 mg rabeprazole. Because of the greater gastric acid secretion-inhibitory effect of 30 mg lansoprazole in recipients having the CYP2C19 *1/*2+*1/*3 (intermediate metabolizer) or MDR1 C3435T CC genotype, the elution and hydrolysis of MMF might be decreased. Although the clinical relevance might be minor, the fact that administration of 30 mg lansoprazole in patients having the CYP2C19 *2 or *3 allele or the MDR1 C3435T CC genotype diminishes the absorption of MPA in the

  2. Simultaneous determination of mycophenolic acid and its glucuronides in human plasma using isocratic ion pair high-performance liquid chromatography.

    PubMed

    Mino, Yasuaki; Naito, Takafumi; Matsushita, Tomomi; Kagawa, Yoshiyuki; Kawakami, Junichi

    2008-02-13

    Therapeutic drug monitoring (TDM) of mycophenolic acid (MPA) following administration of mycophenolate mofetil (MMF) or the enteric-coated sodium salt of MPA formulations, seems beneficial because of the large intra- and inter-individual variability in MPA pharmacokinetics. MPA is an active component from these oral formulations and are further metabolised to inactive phenolic glucuronide (MPAG) and active acyl glucuronide (AcMPAG). This study aims to determine simultaneously these three metabolites of MMF using isocratic ion pair HPLC and to evaluate the short-term stability of AcMPAG in human plasma. Samples were prepared using solid phase extraction. Chromatographic separation was achieved over an RP column (TSKgel ODS-80Ts, 150 mm x 4.6 mm i.d., 5 microm particle size) with acetonitrile and 30 mM tetra-n-butylammonium bromide containing 5 mM ammonium acetate at pH 9.0 (33/67, v/v) as the mobile phase. The flow rate of the mobile phase was 1ml/min, and the wavelength of determination by UV detection was 250 nm (run time, 16 min). Calibration curves for MPA, MPAG and AcMPAG in human plasma were linear over a concentration range of 0.05-50, 0.1-400 and 0.08-8 microg/ml, respectively. Intra- and inter-assay R.S.D. were<6.5%. Extraction efficiencies were more than 85% for all analytes. Since AcMPAG was unstable in human plasma, plasma acidification was needed for the quantification of AcMPAG. Large interindividual variability was observed in the AcMPAG pharmacokinetics in the early period after renal transplantation. In conclusion, a simple, accurate and reproducible HPLC method to measure simultaneously these three MMF metabolites has been established. The method will be helpful in evaluating pharmacokinetics of MPA and its glucuronides.

  3. Stable renal transplant recipients can be safely converted from MMF to enteric-coated mycophenolate sodium tablets: Interim results of a multicenter Latin American study.

    PubMed

    Abbud-Filho, M; Girón, F; Hernández, E; Juarez, F; Liendo, C; Novoa, P; Toledo, M

    2004-01-01

    Enteric-coated mycophenolate sodium (EC-MPS) is designed to reduce mycophenolate acid (MPA)-related upper gastrointestinal (GI) adverse events (AEs). A multicenter, open-label, Latin American study in stable renal transplant patients is ongoing to assess the safety of the conversion from mycophenolate mofetil (MMF) to EC-MPS. An interim analysis was performed when 93 patients had completed 3 months. Prior to conversion, they had received MMF at a dose of 2 g/d, with the exception of eight adult patients who were receiving an average daily dose of 1.25 g. All adult patients were converted to EC-MPS (1.44 g/d; 0.450 g/m(2) bid for children). After conversion, the reported total incidence of AEs was 40.9%, including 28% infections, 1.1% hematologic, 19.4% GI, including 10.8% upper-GI AE (all mild) and 5.4% diarrhea. No patient discontinued the study medication due to adverse events. Only six patients (6%) required a dose adjustment. There were no episodes of acute rejection, death, or graft loss. During the period of analysis, the conversion from MMF to EC-MPS was safe, the enteric-coated tablet formulation prevented release of MPA in the upper GI tract, and only one patient had to reduce the dose due to an upper GI AE, concomitant with diarrhea. EC-MPS offers transplant physicians and their patients an alternative MPA therapy that is as effective and safe as MMF, but in a formulation that may provide GI tolerability benefits.

  4. Treatment of autoimmune hemolytic anemias.

    PubMed

    Zanella, Alberto; Barcellini, Wilma

    2014-10-01

    Autoimmune hemolytic anemia (AIHA) is a relatively uncommon disorder caused by autoantibodies directed against self red blood cells. It can be idiopathic or secondary, and classified as warm, cold (cold hemagglutinin disease (CAD) and paroxysmal cold hemoglobinuria) or mixed, according to the thermal range of the autoantibody. AIHA may develop gradually, or have a fulminant onset with life-threatening anemia. The treatment of AIHA is still not evidence-based. The first-line therapy for warm AIHA are corticosteroids, which are effective in 70-85% of patients and should be slowly tapered over a time period of 6-12 months. For refractory/relapsed cases, the current sequence of second-line therapy is splenectomy (effective approx. in 2 out of 3 cases but with a presumed cure rate of up to 20%), rituximab (effective in approx. 80-90% of cases), and thereafter any of the immunosuppressive drugs (azathioprine, cyclophosphamide, cyclosporin, mycophenolate mofetil). Additional therapies are intravenous immunoglobulins, danazol, plasma-exchange, and alemtuzumab and high-dose cyclophosphamide as last resort option. As the experience with rituximab evolves, it is likely that this drug will be located at an earlier point in therapy of warm AIHA, before more toxic immunosuppressants, and in place of splenectomy in some cases. In CAD, rituximab is now recommended as first-line treatment.

  5. Treatment of lupus nephritis: practical issues in Asian countries.

    PubMed

    Yap, Desmond Y H; Chan, Tak Mao

    2015-02-01

    Lupus nephritis (LN) is a common and severe manifestation of systemic lupus erythematosus in Asian patients, and is an important cause of renal failure in Asian countries. Immunosuppressive treatments of LN have evolved over the past few decades and resulted in improvements in patient outcomes. Treatment guidelines have been recently published by rheumatology and nephrology communities in the USA and Europe, but the emphasis was more on patients of African or Hispanic descent and Caucasians. There is increasing evidence that racial and ethnic variations are associated with differences in disease manifestations, pharmacogenomics/kinetics, response to therapy and complications of disease or treatment. There is substantial data confirming the efficacy of combined corticosteroids and either cyclophosphamide or mycophenolate mofetil (MMF) as initial treatments for active Class III/IV LN in Asian patients. Azathioprine, MMF or a calcineurin inhibitor, or possibly mizoribine which requires further investigation in non-Japanese patients, in combination with low-dose corticosteroids, can be considered as maintenance immunosuppression to prevent disease flares, and the optimal choice needs to take into account tolerability and prior induction therapy. Treatment costs and accessibility to specialist healthcare facilities, compliance which in turn is related to socio-economic and education status, as well as regional variations in risk of infections, including subacute infection such as tuberculosis or chronic infections such as hepatitis B or C, are issues that are distinctly pertinent in Asia.

  6. Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis

    PubMed Central

    Oray, Merih; Tuğal-Tutkun, İlknur

    2016-01-01

    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. PMID:27800265

  7. Complete remission of nephrotic syndrome and acute kidney injury in crescentic IgA nephropathy: Role of mycophenolate sodium

    PubMed Central

    Bhandari, D.; Jhaveri, K. D.; Shah, H. H.

    2016-01-01

    Optimal therapy and prognosis of crescentic-IgA nephropathy (C-IgAN) are not known. Reported treatment options for C-IgAN include combination of corticosteroids and cyclophosphamide for 6 months. The role of mycophenolate sodium in C-IgAN is unknown. We report a case of C-IgAN that was successfully treated with combination immunosuppressive therapy. PMID:27795634

  8. The use of low-dose cyclophosphamide followed by AZA/MMF treatment in childhood lupus nephritis.

    PubMed

    Baskin, Esra; Ozen, Seza; Cakar, Nilgun; Bayrakci, Umut S; Demirkaya, Erkan; Bakkaloglu, Aysin

    2010-01-01

    Cyclophosphamide (CYC) has been the landmark in the treatment of lupus nephritis. However, long-term treatment with CYC is associated with significant side effects. We aimed to evaluate the efficacy of short-term intravenous (IV) CYC treatment as a remission induction treatment followed by azathioprine (AZA) or mycophenolate mofetil (MMF) as a maintenance treatment. Twenty patients (18 girls) with biopsy-proven class III (5) and IV (15) lupus nephritis were included in to the study. Detailed clinical and laboratory data and patient outcomes were evaluated. All patients received three methylprednisolone (MP) IV pulses, followed by oral prednisone 0.5-1 mg/kg per day and one IV pulse of CYC per month for 6 months. Azathioprine was started as a remission-maintaining treatment. In ten of 20 patients, treatment was switched to MMF. The mean age at the time of diagnosis was 16.11 +/- 3.49 years, and the mean duration of follow-up was 49.6 +/- 27 months. Fourteen patients (70%) had complete remission, three (15%) had partial remission, one (5%) continued to have active disease, and two (10%) progressed to end-stage renal disease. Nine of the patients (45%) with complete remission had received AZA, and switching to MMF increased complete remission rate (additional five patients; 25%). In conclusion, short-term (6-month) IV bolus CYC treatment followed by AZA is a safe and effective treatment in children with severe lupus nephritis, and using MMF increases remission rate in resistant cases.

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

    PubMed Central

    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

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

    PubMed

    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.

  11. Validation of limited sampling strategy for the estimation of mycophenolic acid exposure in Chinese adult liver transplant recipients.

    PubMed

    Hao, Chen; Erzheng, Chen; Anwei, Mao; Zhicheng, Yu; Baiyong, Shen; Xiaxing, Deng; Weixia, Zhang; Chenghong, Peng; Hongwei, Li

    2007-12-01

    Mycophenolate mofetil (MMF) is indicated as immunosuppressive therapy in liver transplantation. The abbreviated models for the estimation of mycophenolic acid (MPA) area under the concentration-time curve (AUC) have been established by limited sampling strategies (LSSs) in adult liver transplant recipients. In the current study, the performance of the abbreviated models to predict MPA exposure was validated in an independent group of patients. A total of 30 MPA pharmacokinetic profiles from 30 liver transplant recipients receiving MMF in combination with tacrolimus were used to compare 8 models' performance with a full 10 time-point MPA-AUC. Linear regression analysis and Bland-Altman analysis were used to compare the estimated MPA-AUC0-12h from each model against the measured MPA-AUC0-12h. A wide range of agreement was shown when estimated MPA-AUC0-12h was compared with measured MPA-AUC0-12h, and the range of coefficient of determination (r2) was from 0.479 to 0.936. The model based on MPA pharmacokinetic parameters C1h, C2h, C6h, and C8h had the best ability to predict measured MPA-AUC0-12h, with the best coefficient of determination (r2=0.936), the excellent prediction bias (2.18%), the best prediction precision (5.11%), and the best prediction variation (2SD=+/-7.88 mg.h/L). However, the model based on MPA pharmacokinetic sampling time points C1h, C2h, and C4h was more suitable when concerned with clinical convenience, which had shorter sampling interval, an excellent coefficient of determination (r2=0.795), an excellent prediction bias (3.48%), an acceptable prediction precision (14.37%), and a good prediction variation (2SD=+/-13.23 mg.h/L). Measured MPA-AUC0-12h could be best predicted by using MPA pharmacokinetic parameters C1h, C2h, C6h, and C8h. The model based on MPA pharmacokinetic parameters C1h, C2h, and C4h was more feasible in clinical application.

  12. S2k guideline for treatment of cutaneous lupus erythematosus - guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV).

    PubMed

    Kuhn, A; Aberer, E; Bata-Csörgő, Z; Caproni, M; Dreher, A; Frances, C; Gläser, R; Klötgen, H-W; Landmann, A; Marinovic, B; Nyberg, F; Olteanu, R; Ranki, A; Szepietowski, J C; Volc-Platzer, B

    2017-03-01

    Cutaneous lupus erythematosus (CLE) is a rare inflammatory autoimmune disease with heterogeneous clinical manifestations. To date, no therapeutic agents have been licensed specifically for patients with this disease entity, and topical and systemic drugs are mostly used 'off-label'. The aim of the present guideline was to achieve a broad consensus on treatment strategies for patients with CLE by a European subcommittee, guided by the European Dermatology Forum (EDF) and supported by the European Academy of Dermatology and Venereology (EADV). In total, 16 European participants were included in this project and agreed on all recommendations. Topical corticosteroids remain the mainstay of treatment for localized CLE, and further topical agents, such as calcineurin inhibitors, are listed as alternative first-line or second-line topical therapeutic option. Antimalarials are recommended as first-line and long-term systemic treatment in all CLE patients with severe and/or widespread skin lesions, particularly in patients with a high risk of scarring and/or the development of systemic disease. In addition to antimalarials, systemic corticosteroids are recommended as first-line treatment in highly active and/or severe CLE. Second- and third-line systemic treatments include methotrexate, retinoids, dapsone and mycophenolate mofetil or mycophenolate acid, respectively. Thalidomide should only be used in selected therapy-refractory CLE patients, preferably in addition to antimalarials. Several new therapeutic options, such as B-cell- or interferon α-targeted agents, need to be further evaluated in clinical trials to assess their efficacy and safety in the treatment of patients with CLE.

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

    PubMed

    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.

  14. Treatment of Refractory Chronic Urticaria

    PubMed Central

    Mehta, Aayushi; Godse, Kiran; Patil, Sharmila; Nadkarni, Nitin; Gautam, Manjyot

    2015-01-01

    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. PMID:26120147

  15. Therapeutic drug monitoring of enteric-coated mycophenolate sodium by limited sampling strategies is associated with a high rate of failure

    PubMed Central

    Hougardy, Jean-Michel; Maufort, Laurette; Cotton, Frédéric; Coussement, Julien; Mikhalski, Dimitri; Wissing, Karl M.; Le Moine, Alain; Broeders, Nilufer; Abramowicz, Daniel

    2016-01-01

    Background Therapeutic drug monitoring of mycophenolic acid (MPA) is usually performed with a limited sampling strategy (LSS), which relies on a limited number of blood samples and subsequent extrapolation of the global exposure to MPA. LSS is usually performed successfully with mycophenolate mofetil (MMF), but data on enteric-coated mycophenolate sodium (EC-MPS) are scarce. Here, we evaluated the feasibility of 6-h LSS therapeutic drug monitoring with EC-MPS compared with MMF monitoring among kidney transplant recipients. Methods Sixty-two patients who received EC-MPS during the first 6 months of transplantation were compared with a matched group of 64 MMF-treated kidney transplant recipients. The area under the curve (AUC) was computed by LSS using multiple concentration time points (0, 1, 2, 3 and 6 h post-dose) and a trapezoidal rule. Patients had MPA therapeutic drug monitoring performed on two occasions, one within 2 weeks and the second after 3–4 months of transplantation. Results EC-MPS monitoring and MMF therapeutic drug monitoring were not interpretable in 34.5% (n = 40/116) and 1.8% (n = 2/112) of patients, respectively {relative risk [RR] 19.3 [95% confidence interval (CI) 4.8–78.0]; P < 0.0001}. The main cause of abnormal EC-MPS therapeutic drug monitoring was delayed absorption of both the previous evening and the morning dose, resulting in MPA plasma levels before the next morning dose being higher than MPA plasma levels measured at 1, 2 and 3 h after taking EC-MPS. Cyclosporin in association with MMF significantly increased the risk of low AUC values (<30 mg h/L) in comparison with tacrolimus [55% (n = 11/20) and 10% (n = 9/88), respectively; RR 5.4 (95% CI 2.6–11.2); P < 0.0001]. Conclusions The risk of therapeutic drug monitoring failure with EC-MPS is >30% during the first 6 months of renal transplantation. Delayed pharmacokinetics was the main reason. In contrast, the risk of therapeutic drug monitoring failure was substantially lower with

  16. Severe insulin resistance secondary to insulin antibodies: successful treatment with the immunosuppressant MMF.

    PubMed

    Segal, T; Webb, Ea; Viner, R; Pusey, C; Wild, G; Allgrove, J

    2008-06-01

    We have evaluated the use of the immunosuppressant mycophenolate mofetil (MMF) in the treatment of severe insulin resistance caused by neutralising anti-insulin antibodies in type 1 diabetes mellitus (T1DM). A 12-yr-old boy with a 5-month history of T1DM developed severe immunological insulin resistance secondary to human insulin antibodies. Various different treatment modalities, including lispro insulin, intravenous insulin, prednisolone and immunoabsorption, were tried, all without a sustained response to treatment. Although the introduction of the immunosuppressant MMF only resulted in a small reduction in haemoglobin A1c (from 10.9 to 9.8%), it did result in a significant reduction in insulin requirements from 6000 to 250 U/d (75 to 3.1 U/kg/d), disappearance of the severe nocturnal hypoglycaemia associated with high titres of insulin antibodies and a reduction in the level of these antibodies from 34.6 to 2.7 mg/dL. MMF may be considered as a means of immunosuppression in patients with markedly raised insulin antibodies whose diabetes cannot be controlled with insulin alone.

  17. Structure and mechanism of inosine monophosphate dehydrogenase in complex with the immunosuppressant mycophenolic acid.

    PubMed

    Sintchak, M D; Fleming, M A; Futer, O; Raybuck, S A; Chambers, S P; Caron, P R; Murcko, M A; Wilson, K P

    1996-06-14

    The structure of inosine-5'-monophosphate dehydrogenase (IMPDH) in complex with IMP and mycophenolic acid (MPA) has been determined by X-ray diffraction. IMPDH plays a central role in B and T lymphocyte replication. MPA is a potent IMPDH inhibitor and the active metabolite of an immunosuppressive drug recently approved for the treatment of allograft rejection. IMPDH comprises two domains: a core domain, which is an alpha/beta barrel and contains the active site, and a flanking domain. The complex, in combination with mutagenesis and kinetic data, provides a structural basis for understanding the mechanism of IMPDH activity and indicates that MPA inhibits IMPDH by acting as a replacement for the nicotinamide portion of the nicotinamide adenine dinucleotide cofactor and a catalytic water molecule.

  18. Tacrolimus and Mycophenolate Mofetil With or Without Sirolimus in Preventing Acute Graft-Versus-Host Disease in Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer

    ClinicalTrials.gov

    2016-11-23

    Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndrome; Refractory Chronic Lymphocytic Leukemia; Refractory Plasma Cell Myeloma; Waldenstrom Macroglobulinemia; Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Lymphoma; Childhood Myelodysplastic Syndrome; Stage II Contiguous Adult Burkitt Lymphoma; Stage II Contiguous Adult Diffuse Large Cell Lymphoma; Stage II Contiguous Adult Diffuse Mixed Cell Lymphoma; Stage II Contiguous Adult Diffuse Small Cleaved Cell Lymphoma; Stage II Adult Contiguous Immunoblastic Lymphoma; Stage II Contiguous Adult Lymphoblastic Lymphoma; Stage II Grade 1 Contiguous Follicular Lymphoma; Stage II Grade 2 Contiguous Follicular Lymphoma; Stage II Grade 3 Contiguous Follicular Lymphoma; Stage II Contiguous Mantle Cell Lymphoma; Stage II Non-Contiguous Adult Burkitt Lymphoma; Stage II Non-Contiguous Adult Diffuse Large Cell Lymphoma; Stage II Non-Contiguous Adult Diffuse Mixed Cell Lymphoma; Stage II Non-Contiguous Adult Diffuse Small Cleaved Cell Lymphoma; Stage II Adult Non-Contiguous Immunoblastic Lymphoma; Stage II Non-Contiguous Adult Lymphoblastic Lymphoma; Stage II Grade 1 Non-Contiguous Follicular Lymphoma; Stage II Grade 2 Non-Contiguous Follicular Lymphoma; Stage II Grade 3 Non-Contiguous Follicular Lymphoma; Stage II Non-Contiguous Mantle Cell Lymphoma; Stage II Small Lymphocytic Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Burkitt Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Recurrent Childhood Hodgkin Lymphoma; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Secondary Myelodysplastic Syndrome; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lymphoma; Stage I Adult Immunoblastic Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage I Childhood Anaplastic Large Cell Lymphoma; Stage I Childhood Large Cell Lymphoma; Stage I Childhood Lymphoblastic Lymphoma; Stage I Childhood Burkitt Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Small Lymphocytic Lymphoma; Stage II Childhood Anaplastic Large Cell Lymphoma; Stage II Childhood Lymphoblastic Lymphoma; Stage II Childhood Burkitt Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Immunoblastic Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Childhood Anaplastic Large Cell Lymphoma; Stage III Childhood Large Cell Lymphoma; Stage III Childhood Lymphoblastic Lymphoma; Stage III Childhood Burkitt Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Childhood Anaplastic Large Cell Lymphoma; Stage IV Childhood Large Cell Lymphoma; Stage IV Childhood Lymphoblastic Lymphoma; Stage IV Childhood Burkitt Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma

  19. Sirolimus, Cyclosporine, and Mycophenolate Mofetil in Preventing Graft-versus-Host Disease in Treating Patients With Hematologic Malignancies Undergoing Donor Peripheral Blood Stem Cell Transplant

    ClinicalTrials.gov

    2016-11-03

    Adult Acute Lymphoblastic Leukemia; Adult Acute Myeloid Leukemia; Adult Diffuse Large B-Cell Lymphoma; Adult Myelodysplastic Syndrome; Adult Non-Hodgkin Lymphoma; Aggressive Non-Hodgkin Lymphoma; Childhood Acute Lymphoblastic Leukemia; Childhood Acute Myeloid Leukemia; Childhood Diffuse Large B -Cell Lymphoma; Childhood Myelodysplastic Syndrome; Childhood Non-Hodgkin Lymphoma; Chronic Lymphocytic Leukemia; Chronic Lymphocytic Leukemia in Remission; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Hematopoietic and Lymphoid Cell Neoplasm; Mantle Cell Lymphoma; Plasma Cell Myeloma; Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; T-Cell Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia; Waldenstrom Macroglobulinemia

  20. Fludarabine Phosphate, Low-Dose Total-Body Irradiation, and Donor Stem Cell Transplant Followed by Cyclosporine, Mycophenolate Mofetil, Donor Lymphocyte Infusion in Treating Patients With Hematopoietic Cancer

    ClinicalTrials.gov

    2016-08-01

    Acute Undifferentiated Leukemia; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Juvenile Myelomonocytic Leukemia; Mast Cell Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Myeloid/NK-cell Acute Leukemia; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Primary Systemic Amyloidosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Renal Cell Cancer; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage II Multiple Myeloma; Stage III Multiple Myeloma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  1. Mycophenolate Mofetil and Cyclosporine in Reducing Graft-Versus-Host Disease in Patients With Hematologic Malignancies or Metastatic Kidney Cancer Undergoing Donor Stem Cell Transplant

    ClinicalTrials.gov

    2017-02-27

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Childhood Renal Cell Carcinoma; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Clear Cell Renal Cell Carcinoma; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Juvenile Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Renal Cell Cancer; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Anemia; Refractory Anemia With Ringed Sideroblasts; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Splenic Marginal Zone Lymphoma; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lymphoma; Stage I Adult Immunoblastic Large Cell Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage I Adult T-cell Leukemia/Lymphoma; Stage I Childhood Anaplastic Large Cell Lymphoma; Stage I Childhood Large Cell Lymphoma; Stage I Childhood Lymphoblastic Lymphoma; Stage I Childhood Small Noncleaved Cell Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage II Adult T-cell Leukemia/Lymphoma; Stage II Childhood Anaplastic Large Cell Lymphoma; Stage II Childhood Large Cell Lymphoma; Stage II Childhood Lymphoblastic Lymphoma; Stage II Childhood Small Noncleaved Cell Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Childhood Anaplastic Large Cell Lymphoma; Stage III Childhood Large Cell Lymphoma; Stage III Childhood Lymphoblastic Lymphoma; Stage III Childhood Small Noncleaved Cell Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Childhood Anaplastic Large Cell Lymphoma; Stage IV Childhood Large Cell Lymphoma; Stage IV Childhood Lymphoblastic Lymphoma; Stage IV Childhood Small Noncleaved Cell Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Renal Cell Cancer; T-cell Large Granular Lymphocyte Leukemia; Type 1 Papillary Renal Cell Carcinoma; Type 2 Papillary Renal Cell Carcinoma; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies; Waldenström Macroglobulinemia

  2. Fludarabine Phosphate, Cyclophosphamide, Tacrolimus, Mycophenolate Mofetil, Total-Body Irradiation, and Donor Bone Marrow Transplant in Treating Patients With High-Risk Hematologic Cancer

    ClinicalTrials.gov

    2014-02-27

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hematopoietic/Lymphoid Cancer; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Secondary Myelodysplastic Syndromes; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage II Multiple Myeloma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Childhood Hodgkin Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Multiple Myeloma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Childhood Hodgkin Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small Lymphocytic Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

  3. Alemtuzumab, Fludarabine Phosphate, and Total-Body Irradiation Followed by Cyclosporine and Mycophenolate Mofetil in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer

    ClinicalTrials.gov

    2016-06-13

    Acute Undifferentiated Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Juvenile Myelomonocytic Leukemia; Mast Cell Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Secondary Myelodysplastic Syndromes; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

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

    PubMed

    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.

  5. Developments in the Classification and Treatment of the Juvenile Idiopathic Inflammatory Myopathies

    PubMed Central

    Rider, Lisa G.; Katz, James D.; Jones, Olcay Y.

    2013-01-01

    The juvenile idiopathic inflammatory myopathies (JIIM) are rare, heterogeneous autoimmune diseases that share chronic muscle inflammation and weakness. JIIM broadly includes three major clinicopathologic groups: juvenile dermatomyositis, juvenile polymyositis, and overlap myositis. A growing spectrum of clinicopathologic groups and serologic phenotypes defined by the presence of myositis-specific or myositis-associated autoantibodies are now recognized, each with differing demographics, clinical manifestations, laboratory findings, and prognoses. With the first multi-center collaborative studies and controlled trials using standardized preliminarily validated outcome measures, the therapy of juvenile myositis has advanced. Although daily oral corticosteroids remain the backbone of treatment, disease-modifying anti-rheumatic drugs (DMARDs) are almost always used as adjunctive therapy. Methotrexate is the conventional DMARD for the initial therapy, either alone or combined with intravenous pulse methylprednisolone, and/or intravenous immunoglobulin for patients with moderate to severe disease. Cyclosporine may be added to these or serve as an alternative to methotrexate. Other drugs and biologic therapies, including mycophenolate mofetil, tacrolimus, cyclophosphamide, rituximab, and infliximab, might benefit selected patients with recalcitrant disease, unacceptable steroid toxicity, or patients with risk factors for poor prognosis. The treatment of cutaneous disease, calcinosis, and the role for rehabilitation are also discussed. PMID:24182859

  6. Profile of epratuzumab and its potential in the treatment of systemic lupus erythematosus

    PubMed Central

    Al Rayes, Hanan; Touma, Zahi

    2014-01-01

    Management of systemic lupus erythematosus (SLE) represents a fascinating, emerging field. Research has recently provided us with a better understanding of the immunologic alterations of SLE, leading to the creation of immunomodulatory agents designed to disrupt specific cell targets and pro-inflammatory pathways. Despite the improvement in the prognosis of SLE in the last 50 years with the use of immunosuppressive therapy such as cyclophosphamide and mycophenolate mofetil, cytotoxicity remains a major complication of these medications and the need for more specific targeted immunotherapy is increasing. Early recognition and treatment of SLE with targeted immunotherapy has the potential to improve quality of life and reduce the risk of disease flare-ups and complications. In this review, we will explore the role of B-cells in the pathogenesis of SLE highlighting current insights into SLE development and management. In addition, we will discuss epratuzumab’s role in the treatment of SLE. Epratuzumab is a humanized anti-CD22 monoclonal antibody that targets CD22 on B-cell and its role in B-cell modulation, migration, function, and inhibition of B-cell receptor signaling. Epratuzumab is currently in a Phase III study evaluating its efficacy in the management of moderate to severe SLE. All published trials on epratuzumab have shown great promise with safe profiles. PMID:25429203

  7. The management of pemphigus vulgaris in a burn intensive care unit: a case report and treatment review.

    PubMed

    Miletta, Nathanial; Miller, Mary E; Lam, Thomas; Chung, Kevin K; Hivnor, Chad

    2014-01-01

    Pemphigus vulgaris is a rare, potentially fatal, autoimmune blistering disease of the skin and mucous membranes. Treatment of this disease is problematic because of a lack of high-grade, evidence-based recommendations, the side-effect profiles of the therapies available, and the extensive supportive care that afflicted patients require. The authors present the unfortunate course of a patient with severe pemphigus vulgaris who was admitted to the U.S. Army Institute of Surgical Research Burn Center, to demonstrate the potential complications of therapy. Given the patient's complex course, the authors reviewed the literature and share in this article the most up-to-date treatment recommendations for patients with pemphigus vulgaris. The authors' review of the literature supports using conventional therapy consisting of high-dose corticosteroids and an adjuvant immunosuppressant for mild to moderate cases of pemphigus vulgaris. The immunosuppresants recommended are mycophenolate mofetil, azathioprine, and cyclophosphamide, in order of preference, based on their side-effect profiles and steroid-sparing effects. For severe or recalcitrant cases of pemphigus vulgaris, the authors recommend adding rituximab as early as possible. If increased risk of infection is of particular concern, the use of intravenous immunoglobulin in place of rituximab is advised.

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

    PubMed

    Frimat, L; Cassuto-Viguier, E; Provôt, F; Rostaing, L; Charpentier, B; Akposso, K; Moal, M C; Lang, P; Glotz, D; Caillard, S; Ducloux, D; Pouteil-Noble, C; Girardot-Seguin, S; Kessler, M

    2010-01-01

    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.

  9. Consensus Paper-ICIS Expert Meeting Basel 2009 treatment milestones in immune thrombocytopenia.

    PubMed

    Tamary, Hannah; Roganovic, Jelena; Chitlur, Meera; Nugent, Diane J

    2010-07-01

    The rarity of severe complications of this disease in children makes randomized clinical trials in immune thrombocytopenia (ITP) unfeasible. Therefore, the current management recommendations for ITP are largely dependent on clinical expertise and observations. As part of its discussions during the Intercontinental Cooperative ITP Study Group Expert Meeting in Basel, the Management working group recommended that the decision to treat an ITP patient be individualized and based mainly on bleeding symptoms and not on the actual platelet count number and should be supported by bleeding scores using a validated assessment tool. The group stressed the need to develop a uniform validated bleeding score system and to explore new measures to evaluate bleeding risk in thrombocytopenic patients-the role of rituximab as a splenectomy-sparing agent in resistant disease was also discussed. Given the apparently high recurrence rate to rituximab therapy in children and the drug's possible toxicity, the group felt that until more data are available, a conservative approach may be considered, reserving rituximab for patients who failed splenectomy. More studies of the effectiveness and side effects of drugs to treat refractory patients, such as TPO mimetics, cyclosporine, mycophenolate mofetil, and cytotoxic agents are required, as are long-term data on post-splenectomy complications. In the patient with either acute or chronic ITP, using a more personalized approach to treatment based on bleeding symptoms rather than platelet count should result in less toxicity and empower both physicians and families to focus on quality-of-life.

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

    PubMed Central

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

    2015-01-01

    Background 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. Findings 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. Conclusion 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. PMID:26229512

  11. Suppression of autophagy by mycophenolic acid contributes to inhibition of HCV replication in human hepatoma cells

    PubMed Central

    Fang, Shoucai; Su, Jinming; Liang, Bingyu; Li, Xu; Li, Yu; Jiang, Junjun; Huang, Jiegang; Zhou, Bo; Ning, Chuanyi; Li, Jieliang; Ho, Wenzhe; Li, Yiping; Chen, Hui; Liang, Hao; Ye, Li

    2017-01-01

    Previous studies have shown that mycophenolic acid (MPA) has an anti-HCV activity. However, the mechanism of MPA-mediated inhibition of HCV replication remains to be determined. This study investigated whether MPA has an effect on autophagy, a cellular machinery required for HCV replication, thereby, inhibits HCV replication in Huh7 cells. MPA treatment of Huh7 cells could suppress autophagy, evidenced by decreased LC3B-II level and conversion of LC3B-I to LC3B-II, decreased autophagosome formation, and increased p62 level compared to MPA-untreated cells. Tunicamycin treatment or HCV infection could induce cellular autophagy, however, MPA also exhibited its inhibitory effect on tunicamycin- or HCV infection-induced autophagy. The expression of three autophagy-related genes, Atg3, Atg5, and Atg7 were identified to be inhibited by MPA treatment. Over-expression of these genes could partly recover HCV replication inhibited by MPA; however, silencing their expression by siRNAs could enhance the inhibitory effect of MPA on HCV. Collectively, these results reveal that suppression of autophagy by MPA plays a role in its anti-HCV activity. Down-regulating the expression of three autophagy-related genes by MPA involves in its antiviral mechanism. PMID:28276509

  12. Immunosuppressive treatment for pure membranous lupus nephropathy in a Hispanic population.

    PubMed

    Mejía-Vilet, Juan Manuel; Córdova-Sánchez, Bertha M; Uribe-Uribe, Norma O; Correa-Rotter, Ricardo

    2016-09-01

    Optimal treatment for pure membranous lupus nephritis (MLN) remains unknown. The aim of this study was to evaluate the response to immunosuppressive treatment of Hispanics with pure MLN. This was a retrospective cohort analysis from a tertiary care center. Pure MLN patients were segregated into three groups according to the received induction treatment. All patients received adjunctive steroids. Outcomes included complete remission (CR), partial remission (PR), flare incidence, adverse events, and renal and patient survival. All outcomes were analyzed by Cox regression analysis. A total of 60 patients diagnosed with pure MLN between 2004 and 2014 were segregated into mycophenolate mofetil (MMF) (n = 18), intravenous cyclophosphamide (IVC) (n = 16), or azathioprine (AZA) (n = 26) groups. Complete remission rates at 6, 12, and 24 months were 33.3, 52.9, and 76.4 %, respectively, for MMF; 26.9, 42.3, and 54.6 %, respectively, for AZA; and 6.2, 14.8, and 26.9 %, respectively, for IVC. Based on Cox-adjusted analysis, treatment with MMF was associated with higher CR rates (hazard ratio (HR) 4.43, 1.19-16.4, p = 0.026) compared to IVC. There were no differences in CR rates between MMF and AZA groups. Patients treated with adjunctive antimalarial drugs were more likely to achieve CR (HR 2.46, 1.08-5.64, p = 0.032) and had a non-significant trend to lower incidence of thrombotic events (odds ratio (OR) 0.10, 0.010-1.14, p = 0.064). There were no differences in adverse events, renal flares, and renal or patient survival between groups. MMF might be superior to IVC as induction treatment for pure MLN in Hispanics, while AZA might remain as a valid alternative for treatment. Adjunctive treatment with an antimalarial drug may enhance renal response to therapy.

  13. Novel treatments for systemic lupus erythematosus.

    PubMed

    Gayed, Mary; Gordon, Caroline

    2010-11-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease that is associated with the production of autoantibodies, and with considerable morbidity and mortality. There has been much interest in developing more specific therapies for this disease, which is currently managed with immunosuppressive drugs, predominantly corticosteroids, azathioprine, methotrexate and cyclophosphamide, in combination with hydroxychloroquine. Mycophenolate mofetil has been demonstrated to be as efficacious as cyclophosphamide in patients with lupus nephritis, and is being used increasingly in the clinic despite not being licensed for this indication. Novel methods of reducing autoantibody formation in SLE include the use of mAbs that modulate and/or deplete B-cells (anti-CD22 and anti-CD20 antibodies, respectively), or that interfere with the stimulatory effects of the soluble factor B-lymphocyte stimulator (anti-BLys antibodies). Alternative approaches include the use of atacicept (Merck Serono), a transmembrane activator and calcium modulator ligand interactor (TACI)-Ig fusion protein, which inhibits B-cell stimulation by binding to BLys and a profileration-inducing ligand (APRIL), or toleragens such as abetimus. Blocking costimulatory molecule interactions, such as the CD40-CD40 ligand interaction with mAbs and the CD28-B7 interaction with a soluble cytotoxic T-lymphocyte antigen 4 (CTLA-4)-IgG1 construct (abatacept), has also been attempted as a therapeutic strategy for SLE. The most promising strategy for a new drug for SLE is belimumab (Human Genome Sciences/GlaxoSmithKline), an anti-BLys antibody, as two phase III clinical trials with this drug recently met their primary endpoints. In this review, these novel approaches to the treatment of SLE, including the potential of targeting cytokine pathways involved in autoimmunity, are discussed.

  14. Con: Cyclophosphamide for the treatment of lupus nephritis.

    PubMed

    Mok, Chi Chiu

    2016-07-01

    Kidney involvement is a major determinant for morbidity and mortality in patients with systemic lupus erythematosus. The treatment target of lupus renal disease is to induce and maintain remission and to minimize disease or treatment-related comorbidities. Cyclophosphamide (CYC), in conjunction with glucocorticoids, has conventionally been used for the initial treatment of lupus nephritis. However, the major concerns of CYC are its toxicities, such as infertility, urotoxicity and oncogenicity, which are particularly relevant in women of childbearing age. As a result, maintenance therapy of lupus nephritis with an extended course of CYC pulses has largely been replaced by other immunosuppressive agents such as mycophenolate mofetil (MMF) and azathioprine. Recent randomized controlled trials have demonstrated non-inferiority of MMF to pulse CYC as induction therapy of lupus nephritis. Although MMF as induction-maintenance therapy has been increasingly used in lupus nephritis, its efficacy in the long-term preservation of renal function remains to be elucidated. MMF is not necessarily less toxic than CYC. Meta-analyses of clinical trials show similar incidence of infective complications and gastrointestinal adverse events in both MMF- and CYC-based regimens. However, considering the reduction in gonadal toxicity and the risk of oncogenicity, MMF may be used as first-line therapy of lupus nephritis. Tacrolimus (TAC) has recently been shown to be equivalent to either MMF or CYC for inducing remission of lupus nephritis and may be considered as another non-CYC alternative. Combined low-dose MMF and TAC appears to be more effective than CYC pulses in Chinese patients with lupus nephritis and has the potential to replace the more toxic CYC regimens in high-risk patients. Currently, CYC still plays an important role in the management of lupus nephritis patients with impaired or rapidly deteriorating renal function, crescentic glomerulonephritis or as salvage therapy for

  15. Treatment of young patients with lupus nephritis using calcineurin inhibitors

    PubMed Central

    Tanaka, Hiroshi; Tsuruga, Kazushi; Aizawa-Yashiro, Tomomi; Watanabe, Shojiro; Imaizumi, Tadaatsu

    2012-01-01

    Recent advances in the management of lupus nephritis, together with earlier renal biopsy and selective use of aggressive immunosuppressive therapy, have contributed to a favorable outcome in children and adolescents with systemic lupus erythematosus (SLE). Nevertheless, we believe that a more effective and less toxic treatment is needed to attain an optimal control of the activity of lupus nephritis. Recent published papers and our experiences regarding treatment of young patients with lupus nephritis using calcineurin inhibitors are reviewed. Although it has been reported that intermittent monthly pulses of intravenous cyclophosphamide (IVCY) are effective for preserving renal function in adult patients, CPA is a potent immunosuppressive agent that induces severe toxicity, including myelo- and gonadal toxicity, and increases the risk of secondary malignancy. Thus, treatment for controlling lupus nephritis activity, especially in children and adolescents, remains challenging. Cyclosporine A (CsA) and tacrolimus (Tac) are T-cell-specific calcineurin inhibitors that prevent the activation of helper T cells, thereby inhibiting the transcription of the early activation genes of interleukin (IL)-2 and suppressing T cell-induced activation of tumor necrosis factor-α, IL-1β and IL-6. Therefore, both drugs, which we believe may be less cytotoxic, are attractive therapeutic options for young patients with lupus nephritis. Recently, a multidrug regimen of prednisolone (PDN), Tac, and mycophenolate mofetile (MMF) has been found effective and relatively safe in adult lupus nephritis. Since the mechanisms of action of MMF and Tac are probably complementary, multidrug therapy for lupus nephritis may be useful. We propose as an alternative to IVCY, a multidrug therapy with mizoribine, which acts very similarly to MMF, and Tac, which has a different mode of action, combined with PDN for pediatric-onset lupus nephritis. We also believe that a multidrug therapy including CsA and

  16. Cytoskeletal reorganization by mycophenolic acid alters mesangial cell migration and contractility.

    PubMed

    Dubus, Isabelle; L'Azou, Beatrice; Gordien, Myriam; Delmas, Yahsou; Labouyrie, Jean-Pierre; Bonnet, Jacques; Combe, Christian

    2003-11-01

    Cytoskeleton alterations are a hallmark of mesangial cell activation during glomerulosclerosis. The aim of this study was to investigate whether mycophenolic acid (MPA) affects cytoskeletal organization and motility of human mesangial cells. Using the IP15 cell line, we found that treatment with 1 micromol/L MPA inhibited both receptor-dependent (angiotensin II) and receptor-independent (KCl) contractile responses, as well as serum-induced migration activity, suggesting alterations in the intracellular mechanisms that control mesangial cell motility. Immunofluorescence studies of MPA-treated cells provided evidence for decreased membrane disassembly/reassembly of alpha-smooth muscle actin and F-actin fibers, which was correlated with sustained quantitative and qualitative modifications of actin-associated proteins: calponin was overexpressed and became associated with actin fibers, whereas phosphorylation levels of cofilin and myosin light chain increased, suggesting both an activation of the mechanisms responsible for actin polymerization and an inhibition of actin-depolymerizing processes. These observations support a stabilizing effect of MPA on the mesangial actin cytoskeleton, which constitutes an additive action by which MPA, beyond its anti-inflammatory, antiproliferative and antifibrotic properties, might protect against excessive mesangial activation in the context of various glomerulopathies and kidney transplantation.

  17. Acute promyelocytic leukemia after renal transplant and filgrastim treatment for neutropenia

    PubMed Central

    Krause, John R.

    2016-01-01

    Prolonged immunosuppression in solid organ transplant recipients has been considered a risk for developing opportunistic infections and malignancies. Acute leukemia is a rare complication. We report a case of acute promyelocytic leukemia (APL) (FAB M3) after cadaveric renal transplant for focal segmental glomerulosclerosis in a 24-year-old woman. Her immunosuppressive therapy included tacrolimus, mycophenolate mofetil, and prednisone. Approximately 2 years after transplant, she became pancytopenic, prompting administration of filgrastim. A few doses caused a markedly increased blast count, resulting in a diagnosis of APL. She was successfully treated with all-trans-retinoic acid and arsenic trioxide. Myeloproliferative neoplasms after organ transplant or due to filgrastim are rare. PMID:27695174

  18. Cytoreductive treatment with clofarabine/ara-C combined with reduced-intensity conditioning and allogeneic stem cell transplantation in patients with high-risk, relapsed, or refractory acute myeloid leukemia and advanced myelodysplastic syndrome.

    PubMed

    Buchholz, Stefanie; Dammann, Elke; Stadler, Michael; Krauter, Juergen; Beutel, Gernot; Trummer, Arne; Eder, Matthias; Ganser, Arnold

    2012-01-01

    The combination of cytoreductive chemotherapy with reduced-intensity conditioning (RIC) is a highly effective antileukemic therapy. Purpose of this retrospective analysis was to evaluate the antileukemic efficacy and toxicity of clofarabine-based chemotherapy followed by RIC and allogeneic stem cell transplantation (SCT) for high-risk, relapsed, or refractory acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). From May 2007 until October 2009, a total of 27 patients underwent allogeneic SCT after treatment with clofarabine and ara-C for 5d and RIC (4Gy TBI/cyclophosphamide/ATG). Prophylaxis of graft-versus-host disease (GvHD) consisted of cyclosporine and mycophenolate mofetil. Unmanipulated G-CSF mobilized PBSC (n=26) or bone marrow cells (n=1) were transplanted from unrelated (n=21) or matched related (n=6) donors. Non-hematological toxicities of this regimen mainly affected liver and skin and were all reversible. Seven patients relapsed within a median time of 5.7 months. The overall survival (OS) and relapse-free survival rates were 56% and 52% at 2 yr, respectively. In this cohort of patients, cytoreduction with clofarabine/ara-C (ClAraC) followed by RIC allogeneic SCT was well tolerated and showed good antileukemic efficacy even in patients with high-risk AML or MDS, with engraftment and GvHD-incidence comparable to other RIC regimens.

  19. Determination of mycophenolic acid, penicillic acid, patulin, sterigmatocystin, and aflatoxins in cheese.

    PubMed

    Siriwardana, M G; Lafont, P

    1979-07-01

    A method has been developed for detection of aflatoxins, mycophenolic acid, patulin, penicillic acid, and sterigmatocystin in cheese. It is based on selective extraction with a mixture of equal volumes of 5% sodium chloride, methanol, and aceton, precipitation of caseins at -25 C, defatting with hexane, and removal of extraneous matter by transfer of mycotoxins to chloroform and ethyl acetate. The extract is purified further by column chromatography. Mycotoxins are quantitated on thin layer chromatograms by fluorescence comparisons. Mycophenolic acid, patulin, and penicillic acid are visualized with diethylamine. The limits of detection in cheese are about 20 micrograms/kg for mycophenolic acid, patulin, and sterigmatocystin, 30 microgram/kg for pencillic acid, and 1 microgram/kg for aflatoxins B1 and M1.

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

    PubMed

    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.

  1. Effects of an immunosuppressive treatment on the rat prostate

    PubMed Central

    Grabowska, Marta; Kędzierska, Karolina; Michałek, Katarzyna; Słuczanowska-Głąbowska, Sylwia; Grabowski, Maciej; Piasecka, Małgorzata; Kram, Andrzej; Rotter, Iwona; Rył, Aleksandra; Laszczyńska, Maria

    2016-01-01

    The aim of this study was to determine the influence of different combinations of immunosuppressive drugs on the morphology, ultrastructure, and expression of proliferating cell nuclear antigen and cytoskeleton proteins in the rat dorsolateral prostate. The studies were conducted on 48 male Wistar rats. The animals were divided into eight groups: a control group and seven experimental groups. For 6 months, the animals in the experimental groups were administered a combination of drugs including rapamycin (Rapa), cyclosporin A, tacrolimus (Tac), mycophenolate mofetil, and prednisone (Pred), according to the standard three-drug regimens for immunosuppressive therapy used in clinical practice. An evaluation of the morphology and ultrastructure was conducted, and a quantitative evaluation of the expression of proliferating cell nuclear antigen and desmin- and cytokeratin-positive cells with weak, moderate, and strong expression was performed. The combination of Rapa, Tac, and Pred caused the smallest morphological and ultrastructural changes in the rat prostate cells. In the case of rats whose treatment was switched to Rapa monotherapy, a decreased percentage of proliferating cells of both the glandular epithelium and the stroma was found. Decreases in body weight and changes in the expression of cytokeratin and desmin were observed in all the experimental rats. The combination of Rapa, Tac, and Pred would seem to be the most beneficial for patients who do not suffer from prostate diseases. Our results justify the use of inhibitors of the mammalian target of Rapa in the treatment of patients with prostate cancer. The changes in the expression of cytoskeleton proteins may be the result of direct adverse effects of the immunosuppressive drugs, which are studied in this article, on the structure and organization of intermediate filament proteins. PMID:27672312

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

    PubMed Central

    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

  3. Update on the diagnosis and treatment of neuromyelitis optica: recommendations of the Neuromyelitis Optica Study Group (NEMOS).

    PubMed

    Trebst, Corinna; Jarius, Sven; Berthele, Achim; Paul, Friedemann; Schippling, Sven; Wildemann, Brigitte; Borisow, Nadja; Kleiter, Ingo; Aktas, Orhan; Kümpfel, Tania

    2014-01-01

    Neuromyelitis optica (NMO, Devic's syndrome), long considered a clinical variant of multiple sclerosis, is now regarded as a distinct disease entity. Major progress has been made in the diagnosis and treatment of NMO since aquaporin-4 antibodies (AQP4-Ab; also termed NMO-IgG) were first described in 2004. In this review, the Neuromyelitis Optica Study Group (NEMOS) summarizes recently obtained knowledge on NMO and highlights new developments in its diagnosis and treatment, based on current guidelines, the published literature and expert discussion at regular NEMOS meetings. Testing of AQP4-Ab is essential and is the most important test in the diagnostic work-up of suspected NMO, and helps to distinguish NMO from other autoimmune diseases. Furthermore, AQP4-Ab testing has expanded our knowledge of the clinical presentation of NMO spectrum disorders (NMOSD). In addition, imaging techniques, particularly magnetic resonance imaging of the brain and spinal cord, are obligatory in the diagnostic workup. It is important to note that brain lesions in NMO and NMOSD are not uncommon, do not rule out the diagnosis, and show characteristic patterns. Other imaging modalities such as optical coherence tomography are proposed as useful tools in the assessment of retinal damage. Therapy of NMO should be initiated early. Azathioprine and rituximab are suggested as first-line treatments, the latter being increasingly regarded as an established therapy with long-term efficacy and an acceptable safety profile in NMO patients. Other immunosuppressive drugs, such as methotrexate, mycophenolate mofetil and mitoxantrone, are recommended as second-line treatments. Promising new therapies are emerging in the form of anti-IL6 receptor, anti-complement or anti-AQP4-Ab biologicals.

  4. Successful treatment of ileal ulcers caused by immunosuppressants in two organ transplant recipients

    PubMed Central

    Guo, Yun-Wei; Gu, Hua-Ying; Abassa, Kodjo-Kunale; Lin, Xian-Yi; Wei, Xiu-Qing

    2016-01-01

    Although gastroduodenal ulcers are common in solid organ transplant patients, there are few reports on multiple giant ulcers in the distal ileum and ileocecal valve caused by immunosuppressants Herein, we report on a liver transplant recipient and a renal transplant recipient with multiple large ulcers in the distal ileum and ileocecal valve who rapidly achieved ulcer healing upon withdrawal of sirolimus or tacrolimus and administration of thalidomide. In case 1, a 56-year-old man with primary hepatocellular carcinoma had received a liver transplantation. Tacrolimus combined with sirolimus and prednisolone was used as the anti-rejection regimen. Colonoscopy was performed because of severe abdominal pain and diarrhea at post-operative month 10. Multiple giant ulcers were found at the ileocecal valve and distal ileum. The ulcers healed rapidly with withdrawal of sirolimus and treatment with thalidomide. There was no recurrence during 2 years of follow-up. In case 2, a 34-year-old man with end-stage kidney disease received kidney transplantation and was put on tacrolimus combined with mycophenolate mofetil and prednisolone as the anti-rejection regimen. Twelve weeks after the operation, the patient presented with hematochezia and severe anemia. Colonoscopy revealed multiple large ulcers in the ileocecal valve and distal ileum, with massive accumulation of fresh blood. The bleeding ceased after treatment with intravenous somatostatin and oral thalidomide. Tacrolimus was withdrawn at the same time. Colonoscopy at week 4 of follow-up revealed remarkable healing of the ulcers, and there was no recurrence of bleeding during 1 year of follow-up. No lymphoma, tuberculosis, or infection of cytomegalovirus, Epstein-Barr virus, or fungus was found in either patient. In post-transplantation cases with ulcers in the distal ileum and ileocecal valve, sirolimus or tacrolimus should be considered a possible risk factor, and withdrawing them or switching to another immunosuppressant

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

    PubMed

    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.

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

    PubMed Central

    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

    Background 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. Methods 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. Results 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. Conclusion 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. PMID:27471376

  7. Identifying the differences in mechanisms of mycophenolic acid controlling fucose content of glycoproteins expressed in different CHO cell lines.

    PubMed

    Zhang, An; Tsang, Valerie Liu; Markely, Lam R; Kurt, Lutfiye; Huang, Yao-Ming; Prajapati, Shashi; Kshirsagar, Rashmi

    2016-11-01

    In the biopharmaceutical industry, glycosylation is a critical quality attribute that can modulate the efficacy of a therapeutic glycoprotein. Obtaining a consistent glycoform profile is desired because molecular function can be defined by its carbohydrate structures. Specifically, the fucose content of oligosaccharides in glycoproteins is one of the most important attributes that can significantly affect antibody-dependent cellular cytotoxicity (ADCC) activity. It is therefore important to understand the fucosylation pathway and be able to control fucosylation at the desired level to match predecessor materials in late stage and biosimilar programs. Several strategies were explored in this study and mycophenolic acid (MPA) was able to finely modulate the fucose content with the least undesired side effects. However, the response was significantly different between CHO cell lines of different lineages. Further experiments were then performed for a deeper understanding of the mechanism of fucosylation in different CHO cell lines. Results indicated that changes in the intracellular nucleotide involved in fucosylation pathway after MPA treatment are the main cause of the differences in fucosylation level response in different CHO cell lines. Differences in MPA metabolism in the various CHO cell lines directly resulted in different levels of afucosylation measured in antibodies produced by the CHO cell lines. Biotechnol. Bioeng. 2016;113: 2367-2376. © 2016 Wiley Periodicals, Inc.

  8. Drug-drug interactions between immunosuppressants and antidiabetic drugs in the treatment of post-transplant diabetes mellitus.

    PubMed

    Vanhove, Thomas; Remijsen, Quinten; Kuypers, Dirk; Gillard, Pieter

    2016-09-14

    Post-transplant diabetes mellitus is a frequent complication of solid organ transplantation that generally requires treatment with lifestyle interventions and antidiabetic medication. A number of demonstrated and potential pharmacokinetic drug-drug interactions (DDIs) exist between commonly used immunosuppressants and antidiabetic drugs, which are comprehensively summarized in this review. Cyclosporine (CsA) itself inhibits the cytochrome P450 (CYP) 3A4 enzyme and a variety of drug transporters. As a result, it increases exposure to repaglinide and sitagliptin, will likely increase the exposure to nateglinide, glyburide, saxagliptin, vildagliptin and alogliptin, and could theoretically increase the exposure to gliquidone and several sodium-glucose transporter (SGLT)-2 inhibitors. Currently available data, although limited, suggest that these increases are modest and, particularly with regard to gliptins and SGLT-2 inhibitors, unlikely to result in hypoglycemia. The interaction with repaglinide is more pronounced but does not preclude concomitant use if repaglinide dose is gradually titrated. Mycophenolate mofetil and azathioprine do not engage in DDIs with any antidiabetic drug. Although calcineurin inhibitors (CNIs) and mammalian target of rapamycin inhibitors (mTORi) are intrinsically prone to DDIs, their disposition is not influenced by metformin, pioglitazone, sulfonylureas (except possibly glyburide) or insulin. An effect of gliptins on the disposition of CNIs and mTORi is unlikely, but has not been definitively ruled out. Based on their disposition profiles, glyburide and canagliflozin could affect CNI and mTORi disposition although this requires further study. Finally, delayed gastric emptying as a result of glucagon-like peptide-1 agonists seems to have a limited, but not necessarily negligible effect on CNI disposition.

  9. Iodine I 131 Monoclonal Antibody BC8, Fludarabine Phosphate, Total Body Irradiation, and Donor Stem Cell Transplant Followed by Cyclosporine and Mycophenolate Mofetil in Treating Patients With Advanced Acute Myeloid Leukemia or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2016-11-14

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ringed Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  10. Fludarabine Phosphate, Cyclophosphamide, Total-Body Irradiation, and Donor Bone Marrow Transplant Followed by Donor Natural Killer Cell Therapy, Mycophenolate Mofetil, and Tacrolimus in Treating Patients With Hematologic Cancer

    ClinicalTrials.gov

    2016-06-07

    Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Aggressive Non-Hodgkin Lymphoma; Diffuse Large B-Cell Lymphoma; Previously Treated Myelodysplastic Syndrome; Recurrent Chronic Lymphocytic Leukemia; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Recurrent Indolent Adult Non-Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Plasma Cell Myeloma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hodgkin Lymphoma; Refractory Plasma Cell Myeloma; Refractory Small Lymphocytic Lymphoma; Waldenstrom Macroglobulinemia

  11. Tacrolimus and Mycophenolate Mofetil in Preventing Graft-Versus-Host Disease in Patients Who Have Undergone Total-Body Irradiation With or Without Fludarabine Phosphate Followed by Donor Peripheral Blood Stem Cell Transplant for Hematologic Cancer

    ClinicalTrials.gov

    2016-01-25

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Phase Chronic Myelogenous Leukemia; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Polycythemia Vera; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Prolymphocytic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lymphoma; Stage I Adult Diffuse Small Cleaved Cell Lymphoma; Stage I Adult Immunoblastic Large Cell Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage I Adult T-cell Leukemia/Lymphoma; Stage I Childhood Anaplastic Large Cell Lymphoma; Stage I Childhood Large Cell Lymphoma; Stage I Childhood Lymphoblastic Lymphoma; Stage I Childhood Small Noncleaved Cell Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Multiple Myeloma; Stage I Small Lymphocytic Lymphoma; Stage IA Mycosis Fungoides/Sezary Syndrome; Stage IB Mycosis Fungoides/Sezary Syndrome; Stage II Adult T-cell Leukemia/Lymphoma; Stage II Childhood Anaplastic Large Cell Lymphoma; Stage II Childhood Large Cell Lymphoma; Stage II Childhood Lymphoblastic Lymphoma; Stage II Childhood Small Noncleaved Cell Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage II Multiple Myeloma; Stage IIA Mycosis Fungoides/Sezary Syndrome; Stage IIB Mycosis Fungoides/Sezary Syndrome; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Childhood Anaplastic Large Cell Lymphoma; Stage III Childhood Large Cell Lymphoma; Stage III Childhood Lymphoblastic Lymphoma; Stage III Childhood Small Noncleaved Cell Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Multiple Myeloma; Stage III Small Lymphocytic Lymphoma; Stage IIIA Mycosis Fungoides/Sezary Syndrome; Stage IIIB Mycosis Fungoides/Sezary Syndrome; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Childhood Anaplastic Large Cell Lymphoma; Stage IV Childhood Large Cell Lymphoma; Stage IV Childhood Lymphoblastic Lymphoma; Stage IV Childhood Small Noncleaved Cell Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma; Stage IVA Mycosis Fungoides/Sezary Syndrome; Stage IVB Mycosis Fungoides/Sezary Syndrome; Testicular Lymphoma; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies; Waldenström Macroglobulinemia

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

    PubMed Central

    Kędzierska, Karolina; Sporniak-Tutak, Katarzyna; Sindrewicz, Krzysztof; Bober, Joanna; Domański, Leszek; Parafiniuk, Mirosław; Urasińska, Elżbieta; Ciechanowicz, Andrzej; Domański, Maciej; Smektała, Tomasz; Masiuk, Marek; Skrzypczak, Wiesław; Ożgo, Małgorzata; Kabat-Koperska, Joanna; Ciechanowski, Kazimierz

    2014-01-01

    The structural proteins of renal tubular epithelial cells may become a target for the toxic metabolites of immunosuppressants. These metabolites can modify the properties of the proteins, thereby affecting cell function, which is a possible explanation for the mechanism of immunosuppressive agents’ toxicity. In our study, we evaluated the effect of two immunosuppressive strategies on protein expression in the kidneys of Wistar rats. Fragments of the rat kidneys were homogenized after cooling in liquid nitrogen and then dissolved in lysis buffer. The protein concentration in the samples was determined using a protein assay kit, and the proteins were separated by two-dimensional electrophoresis. The obtained gels were then stained with Coomassie Brilliant Blue, and their images were analyzed to evaluate differences in protein expression. Identification of selected proteins was then performed using mass spectrometry. We found that the immunosuppressive drugs used in popular regimens induce a series of changes in protein expression in target organs. The expression of proteins involved in drug, glucose, amino acid, and lipid metabolism was pronounced. However, to a lesser extent, we also observed changes in nuclear, structural, and transport proteins’ synthesis. Very slight differences 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

  13. Determination of Mycophenolic Acid in Plasma Samples Using the Terbium-Sensitized Luminescence Method

    NASA Astrophysics Data System (ADS)

    Shayanfar, A.; Ghavimi, H.; Zolali, E.; Jouyban, A.

    2015-09-01

    The objectives of this work were to provide an analytical method, for the quantitative determination of the mycophenolic acid (MFA) in plasma samples and its application to quantification of the MFA in rat plasma after oral administration. In order to remove the fluorescence interferences of the plasma, the samples were precipitated by acetonitrile in 1:8 ratio and then a few parameters were optimized and the fluorescence intensity measured at 545 nm using an excitation wavelength of 347 nm. Under the optimized concentration, the method provided a linear range between 1.0 and 10.0 mg/l with a correlation coefficient of 0.998. MFA was detected and the validation was performed according to the FDA guidelines. Linearity, accuracy, precision, and selectivity of the developed method were suitable for th determination of the MFA in plasma samples. The proposed analytical approach was applied to determine the MFA concentration in a rat plasma-time profile study.

  14. Polymerase chain reaction (PCR) identification of Penicillium brevicompactum, a grape contaminant and mycophenolic acid producer.

    PubMed

    Patiño, B; Medina, A; Doménech, M; González-Jaén, M T; Jiménez, M; Vázquez, C

    2007-02-01

    Penicillium brevicompactum is a ubiquitous fungal species that contaminates diverse substrates and commodities and produces an array of metabolites toxic to human and animals. The present work has obtained evidence, by liquid chromatography (LC)-ion-trap mass spectrometry, of the ability of P. brevicompactum strains isolated from grapes to produce mycophenolic acid, a potent immunosuppressor. In order to facilitate early diagnosis of this species on commodities for human and animal consumption, a rapid, sensitive and specific polymerase chain reaction (PCR) assay for P. brevicompactum was developed. The specific primers were designed based on the ITS1-5.8S-ITS2ITS (Internal Transcribed Spacers of rRNA genes) multicopy region. This method provides a useful aid to detect the presence of this fungal species in grapes and other commodities in order to prevent the toxins produced entering the food chain.

  15. Estimation of Mycophenolic Acid Area Under the Curve With Limited-Sampling Strategy in Chinese Renal Transplant Recipients Receiving Enteric-Coated Mycophenolate Sodium

    PubMed Central

    Jia, Yichen; Peng, Bo; Li, Long; Wang, Jina; Wang, Xuanchuan; Qi, Guisheng; Rong, Ruiming; Wang, Liming; Qiu, Jianxin; Xu, Ming

    2017-01-01

    Background: The enteric-coated mycophenolate sodium (EC-MPS), whose active constituent is mycophenolic acid (MPA), has been widely clinically used for organ transplant recipients. However, its absorption is delayed due to its special designed dosage form, which results in difficulty to monitor the exposure of the MPA in patients receiving the EC-MPS. This study was aimed at developing a relatively practical and precise model with limited sampling strategy to estimate the 12-hour area under the concentration–time curve (AUC0–12 h) of MPA for Chinese renal transplant recipients receiving EC-MPS. Methods: A total of 36 Chinese renal transplant recipients receiving the EC-MPS and tacrolimus were recruited in this study. The time point was 2 weeks after the transplantation for all the patients. The MPA concentrations were measured with enzyme-multiplied immunoassay technique for 11 blood specimens collected predose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the morning dose of EC-MPS. The measured AUC was calculated with these 11 points of MPA concentrations with the linear trapezoidal rule. Limited sampling strategy was used to develop models for estimated AUC in the model group (n = 18). The bias and precision of different models were evaluated in the validation group (n = 18). Results: C4 showed the strongest correlation with the measured AUC. The best 3 time point equation was 6.629 + 8.029 × C0 + 0.592 × C3 + 1.786 × C4 (R2 = 0.910; P < 0.001), whereas the best 4 time point equation was 3.132 + 5.337 × C0 + 0.735 × C3 + 1.783 × C4 + 3.065 × C8 (R2 = 0.959; P < 0.001). When evaluated in the validation group, the 4 time point model had a much better performance than the 3 time point model: for the 4 time point model: R2 = 0.873, bias = 0.505 [95% confidence interval (CI), −10.159 to 11.170], precision = 13.370 (95% CI, 5.186–21.555), and 77.8% of estimated AUCs was within 85%–115% of the measured AUCs; for the 3 time point model: R2

  16. Simultaneous determination of mycophenolic acid and its glucuronide and glycoside derivatives in canine and feline plasma by UHPLC-UV.

    PubMed

    Rivera, Sol Maiam; Hwang, Julianne K; Slovak, Jeniffer E; Court, Michael H; Villarino, Nicolas F

    2017-02-01

    Cats and dogs can suffer from multiple autoimmune diseases. Mycophenolic acid (MPA) is a potentially useful immunosuppressant drug in cats and dogs, because of its well-documented efficacy in controlling autoimmune disease in humans. However, the pharmacokinetics and pharmacodynamics in these species remain to be determined. We have developed and validated a sensitive, precise, accurate and reproducible method that provides consistent quantification of MPA and its major derivatives, MPA phenol glucoside and MPA phenol glucuronide, in canine and feline plasma using ultra-high-pressure liquid chromatography coupled to an ultraviolet detector. The main advantages of this novel method include a small sample volume, easy sample preparation, a short chromatographic analysis time and the option to select either phenolphthalein β-d-glucuronide or mycophenolic acid carboxybutoxy ether as internal standard. Results of validation indicate that this analytical method is suitable to study the plasma disposition of MPA and its derivatives in dogs and cats.

  17. The Immunosuppressant Mycophenolic Acid Alters Nucleotide and Lipid Metabolism in an Intestinal Cell Model

    PubMed Central

    Heischmann, Svenja; Dzieciatkowska, Monika; Hansen, Kirk; Leibfritz, Dieter; Christians, Uwe

    2017-01-01

    The study objective was to elucidate the molecular mechanisms underlying the negative effects of mycophenolic acid (MPA) on human intestinal cells. Effects of MPA exposure and guanosine supplementation on nucleotide concentrations in LS180 cells were assessed using liquid chromatography-mass spectrometry. Proteomics analysis was carried out using stable isotope labeling by amino acids in cell culture combined with gel-based liquid chromatography-mass spectrometry and lipidome analysis using 1H nuclear magnetic resonance spectroscopy. Despite supplementation, depletion of guanosine nucleotides (p < 0.001 at 24 and 72 h; 5, 100, and 250 μM MPA) and upregulation of uridine and cytidine nucleotides (p < 0.001 at 24 h; 5 μM MPA) occurred after exposure to MPA. MPA significantly altered 35 proteins mainly related to nucleotide-dependent processes and lipid metabolism. Cross-reference with previous studies of MPA-associated protein changes widely corroborated these results, but showed differences that may be model- and/or method-dependent. MPA exposure increased intracellular concentrations of fatty acids, cholesterol, and phosphatidylcholine (p < 0.01 at 72 h; 100 μM MPA) which corresponded to the changes in lipid-metabolizing proteins. MPA affected intracellular nucleotide levels, nucleotide-dependent processes, expression of structural proteins, fatty acid and lipid metabolism in LS180 cells. These changes may compromise intestinal membrane integrity and contribute to gastrointestinal toxicity. PMID:28327659

  18. Virtual High-Throughput Screening Identifies Mycophenolic Acid as a Novel RNA Capping Inhibitor

    PubMed Central

    Tremblay-Létourneau, Maude; Despins, Simon; Bougie, Isabelle; Bisaillon, Martin

    2011-01-01

    The RNA guanylyltransferase (GTase) is involved in the synthesis of the m7Gppp-RNA cap structure found at the 5′ end of eukaryotic mRNAs. GTases are members of the covalent nucleotidyl transferase superfamily, which also includes DNA and RNA ligases. GTases catalyze a two-step reaction in which they initially utilize GTP as a substrate to form a covalent enzyme-GMP intermediate. The GMP moiety is then transferred to the diphosphate end of the RNA transcript in the second step of the reaction to form the Gppp-RNA structure. In the current study, we used a combination of virtual database screening, homology modeling, and biochemical assays to search for novel GTase inhibitors. Using this approach, we demonstrate that mycophenolic acid (MPA) can inhibit the GTase reaction by preventing the catalytic transfer of the GMP moiety onto an acceptor RNA. As such, MPA represents a novel type of inhibitor against RNA guanylyltransferases that inhibits the second step of the catalytic reaction. Moreover, we show that the addition of MPA to S. cerevisiae cells leads to a reduction of capped mRNAs. Finally, biochemical assays also demonstrate that MPA can inhibit DNA ligases through inhibition of the second step of the reaction. The biological implications of these findings for the MPA-mediated inhibition of members of the covalent nucleotidyl superfamily are discussed. PMID:21935470

  19. An additional Meyerozyma guilliermondii IMH3 gene confers mycophenolic acid resistance in fungal CTG clade species.

    PubMed

    Defosse, Tatiana A; Mélin, Céline; Clastre, Marc; Besseau, Sébastien; Lanoue, Arnaud; Glévarec, Gaëlle; Oudin, Audrey; Dugé de Bernonville, Thomas; Vandeputte, Patrick; Linder, Tomas; Bouchara, Jean-Philippe; Courdavault, Vincent; Giglioli-Guivarc'h, Nathalie; Papon, Nicolas

    2016-09-01

    The fungal CTG clade comprises a number of well-known yeasts that impact human health or with high biotechnological potential. To further extend the set of molecular tools dedicated to these microorganisms, the initial focus of this study was to develop a mycophenolic acid (MPA) resistance cassette. Surprisingly, while we were carrying out preliminary susceptibility testing experiments in a set of yeast species, Meyerozyma guilliermondii, although not being a MPA producer, was found to be primarily resistant toward this drug, whereas a series of nine related species were susceptible to MPA. Using comparative and functional genomic approaches, we demonstrated that all MPA-susceptible CTG clade species display a single gene, referred to as IMH3.1, encoding the MPA target inosine monophosphate dehydrogenase (IMPDH) and that MPA resistance relies on the presence in the M. guilliermondii genome of an additional IMPDH-encoding gene (IMH3.2). The M. guilliermondii IMH3.2 gene displays marked differences compared to IMH3.1 including the lack of intron, a roughly 160-fold higher transcription level and a serine residue at position 251. Placed under the control of the M. guilliermondii actin 1 gene promoter, IMH3.2 was successfully used to transform Lodderomyces elongisporus, Clavispora lusitaniae, Scheffersomyces stipitis and Candida parapsilosis.

  20. Clinicopathologic features and outcome of mycophenolate-induced colitis in renal transplant recipients.

    PubMed

    de Andrade, Luis Gustavo M; Rodrigues, Maria Aparecida M; Romeiro, Fernando G; Garcia, Paula D; Contti, Mariana M; de Carvalho, Maria Fernanda C

    2014-11-01

    Reports on the clinical course of mycophenolic acid (MPA)-related colitis in kidney transplant recipients are scarce. This study aimed at assessing MPA-related colitis incidence, risk factors, and progression after kidney transplantation. All kidney transplant patients taking MPA who had colonic biopsies for persistent chronic diarrhea, between 2000 and 2012, at the Kidney Transplantation Unit of Botucatu Medical School Hospital, Brazil, were included. Cytomegalovirus (CMV) immunohistochemistry was performed in all biopsy specimens. Data on presenting symptoms, medications, immunosuppressive drugs, colonoscopic findings, and follow-up were obtained. Of 580 kidney transplant patients on MPA, 34 underwent colonoscopy. Colonoscopic findings were associated with MPA usage in 16 patients. The most frequent histologic patterns were non-specific colitis (31.3%), inflammatory bowel disease (IBD)-like colitis (25%), normal/near normal (18.8%), graft-versus-host disease-like (18.8%), and ischemia-like colitis (12.5%). All patients had persistent acute diarrhea and weight loss. Six of the 16 MPA-related diarrhea patients (37.5%) showed acute dehydration requiring hospitalization. Diarrhea resolved when MPA was switched to sirolimus (50%), discontinued (18.75%), switched to azathioprine (12.5%), or reduced by 50% (18.75%). No graft loss occurred. Four patients died during the study period. Late-onset MPA was more frequent, and no correlation with MPA dose or formulation was found.

  1. Investigations on the immunosuppressive activity of derivatives of mycophenolic acid in immature dendritic cells.

    PubMed

    Iwaszkiewicz-Grzes, Dorota; Cholewinski, Grzegorz; Kot-Wasik, Agata; Trzonkowski, Piotr; Dzierzbicka, Krystyna

    2017-03-01

    The main activity of mycophenolic acid 1 (MPA) and its analogs is the inhibition of proliferation of T cells. Here, we hypothesized that MPA and its conjugates inhibits also the activity of antigen-presenting cells (APC) including dendritic cells (DCs). We tested the effect of novel amino acid derivatives of MPA and conjugates of MPA with acridines/acridones on DCs by flow cytometry, ELISA and MLR assay. Both acridines/acridone derivatives could inhibit the maturation of DC, as shown by the decreased expression of B7 family receptors. It was confirmed in the mixed leucocyte reaction (MLR), in which T cells challenged with DCs pretreated with the analogs showed decreased proliferation and reduced cytokine secretion. The most interesting activity in this series of studies, that is, the suppression of CD86 receptor expression, decreased cytokine production and suppressed mixed leucocyte reaction, exhibited (mycophenoyl-N-3-propyl)-9-acridone-4-carboxamide ester 5a and (mycophenoyl-N-5-pentyl)-9-acridone-4-carboxamide ester 5b. These compounds reduced also the secretion of IL-2 and IL-15. In addition, they increased secretion of suppressive IL-10. Equally promising results were obtained for the N-mycophenoyl-D-glutamic acid 4b, which previously gave the highest value of selectivity. Acridone derivatives of MPA are therefore good immunosuppressive drug candidates for further testing.

  2. Strain-Specific Synthesis of Mycophenolic Acid by Penicillium roqueforti in Blue-Veined Cheese

    PubMed Central

    Engel, Günter; von Milczewski, Karl Ernst; Prokopek, Dieter; Teuber, Michael

    1982-01-01

    Twenty of 80 strains of Penicillium roqueforti were able to produce up to 600 mg of mycophenolic acid (MPA) liter−1 in 2% yeast extract-5% sucrose broth. Sixty-two of these strains had been isolated from the main blue-veined cheese varieties of western Europe or from starter cultures. Of these 62 dairy strains, only 7 had MPA-producing potential in vitro. These seven strains had all been isolated during the period 1975 to 1981 from the blue cheese of one individual factory. In cheese from the market, MPA (up to 5 mg kg−1) was only found in samples of this same factory. With MPA-producing and -nonproducing strains for the experimental manufacture of blue cheese, MPA synthesis in cheese was only detected with strains which form MPA in yeast extract-sucrose broth. The maximum MPA level at 4 mg kg−1 was similar to that in commercial cheese. Toxicity of MPA was tested with two established human cell lines (Detroit 98 and Girardi Heart) and one established pig kidney cell line (AmII). PMID:16346004

  3. Pharmacokinetics and target attainment of mycophenolate in pediatric renal transplant patients.

    PubMed

    Martial, Lisa C; Jacobs, Bart A W; Cornelissen, Elisabeth A M; de Haan, Anton F J; Koch, Birgit C P; Burger, David M; Aarnoutse, Rob E; Schreuder, Michiel F; Brüggemann, Roger J M

    2016-06-01

    MPA is an immunosuppressive agent used to prevent graft rejection after renal transplantation. MPA shows considerable inter- and intraindividual variability in exposure in children and has a defined therapeutic window, and TDM is applied to individualize therapy. We aimed to study the exposure to MPA measured as the AUC in pediatric renal transplant patients, to identify factors influencing exposure and to assess target attainment. Children transplanted between 1998 and 2014 in a single center were included. Two groups were identified: Group 1 (AUC <3 wk post-transplantation) and Group 2 (AUC >18 months post-transplantation). Therapeutic targets were set at: AUC0-12h of 30-60 mg h/L. A total of 39 children were included in Group 1 (median age 13.3 yr) vs. 14 in Group 2 (median age 13.4 yr). AUC0-12h was 29.7 mg h/L in Group 1 and 56.6 mg h/L in Group 2, despite a lower dosage in Group 2 (584 and 426 mg/m(2) , respectively). About 46% of patients reached the target AUC0-12h in Group 1. Time since transplantation and serum creatinine were significantly associated with MPA exposure (p < 0.001), explaining 36% of the variability. Individualization of the mycophenolate dose by more intense and more early TDM could improve target attainment.

  4. Identification and Functional Analysis of the Mycophenolic Acid Gene Cluster of Penicillium roqueforti.

    PubMed

    Del-Cid, Abdiel; Gil-Durán, Carlos; Vaca, Inmaculada; Rojas-Aedo, Juan F; García-Rico, Ramón O; Levicán, Gloria; Chávez, Renato

    2016-01-01

    The filamentous fungus Penicillium roqueforti is widely known as the ripening agent of blue-veined cheeses. Additionally, this fungus is able to produce several secondary metabolites, including the meroterpenoid compound mycophenolic acid (MPA). Cheeses ripened with P. roqueforti are usually contaminated with MPA. On the other hand, MPA is a commercially valuable immunosuppressant. However, to date the molecular basis of the production of MPA by P. roqueforti is still unknown. Using a bioinformatic approach, we have identified a genomic region of approximately 24.4 kbp containing a seven-gene cluster that may be involved in the MPA biosynthesis in P. roqueforti. Gene silencing of each of these seven genes (named mpaA, mpaB, mpaC, mpaDE, mpaF, mpaG and mpaH) resulted in dramatic reductions in MPA production, confirming that all of these genes are involved in the biosynthesis of the compound. Interestingly, the mpaF gene, originally described in P. brevicompactum as a MPA self-resistance gene, also exerts the same function in P. roqueforti, suggesting that this gene has a dual function in MPA metabolism. The knowledge of the biosynthetic pathway of MPA in P. roqueforti will be important for the future control of MPA contamination in cheeses and the improvement of MPA production for commercial purposes.

  5. Pharmacokinetics, Electrophysiological, and Morphological Effects of the Intravitreal Injection of Mycophenolic Acid in Rabbits

    PubMed Central

    Gasparin, Fabio; Aguiar, Renata Genaro; Ioshimoto, Gabriela Lourençon; Silva-Cunha, Armando; Fialho, Silvia Ligório; Liber, André Mauricio; Nagy, Balázs Vince; Oiwa, Nestor Norio; Costa, Marcelo Fernandes; Joselevitch, Christina; Ventura, Dora Fix

    2014-01-01

    Abstract Purpose: To determine the half-life of mycophenolic acid (MPA) in the vitreous of New Zealand albino rabbits after intravitreal injection and the retinal toxicity of different doses of MPA. Methods: Ten micrograms of MPA (Roche Bioscience, Palo Alto, CA) was injected in the vitreous of 16 rabbits, animals were sacrificed at different time-points, and vitreous samples underwent high-performance liquid chromatography. For functional and morphological studies, 5 doses of MPA (0.05, 0.5, 2, 10, and 100 μg) were injected in the vitreous of 20 rabbits. As control, contralateral eyes were injected with aqueous vehicle. Electroretinograms (ERGs) were recorded before injection and at days 7, 15, and 30. Animals were sacrificed on day 30 and retinas were analyzed under light microscopy. Results: MPA half-life in the vitreous was 5.0±0.3 days. ERG revealed photoreceptor functional impairment in eyes injected with 0.5 μg and higher on day 30, while eyes injected with 100 μg presented the same changes already from day 15. No morphological change was found. Conclusions: MPA vitreous half-life is 5.0 days. Intravitreal injection of 0.5 μg MPA and higher causes dose- and time-related photoreceptor sensitivity decrease in rabbits. The MPA dose of 0.05 μg may be safe for intravitreal use in rabbits. PMID:24828287

  6. Identification and Functional Analysis of the Mycophenolic Acid Gene Cluster of Penicillium roqueforti

    PubMed Central

    Del-Cid, Abdiel; Gil-Durán, Carlos; Vaca, Inmaculada; Rojas-Aedo, Juan F.; García-Rico, Ramón O.; Levicán, Gloria; Chávez, Renato

    2016-01-01

    The filamentous fungus Penicillium roqueforti is widely known as the ripening agent of blue-veined cheeses. Additionally, this fungus is able to produce several secondary metabolites, including the meroterpenoid compound mycophenolic acid (MPA). Cheeses ripened with P. roqueforti are usually contaminated with MPA. On the other hand, MPA is a commercially valuable immunosuppressant. However, to date the molecular basis of the production of MPA by P. roqueforti is still unknown. Using a bioinformatic approach, we have identified a genomic region of approximately 24.4 kbp containing a seven-gene cluster that may be involved in the MPA biosynthesis in P. roqueforti. Gene silencing of each of these seven genes (named mpaA, mpaB, mpaC, mpaDE, mpaF, mpaG and mpaH) resulted in dramatic reductions in MPA production, confirming that all of these genes are involved in the biosynthesis of the compound. Interestingly, the mpaF gene, originally described in P. brevicompactum as a MPA self-resistance gene, also exerts the same function in P. roqueforti, suggesting that this gene has a dual function in MPA metabolism. The knowledge of the biosynthetic pathway of MPA in P. roqueforti will be important for the future control of MPA contamination in cheeses and the improvement of MPA production for commercial purposes. PMID:26751579

  7. The Effect of Tacrolimus and Mycophenolic Acid on CD14+ Monocyte Activation and Function

    PubMed Central

    Kannegieter, Nynke M.; Hesselink, Dennis A.; Dieterich, Marjolein; Kraaijeveld, Rens; Rowshani, Ajda T.; Leenen, Pieter J. M.; Baan, Carla C.

    2017-01-01

    Monocytes and macrophages play key roles in many disease states, including cellular and humoral rejection after solid organ transplantation (SOT). To suppress alloimmunity after SOT, immunosuppressive drug therapy is necessary. However, little is known about the effects of the immunosuppressive drugs tacrolimus and mycophenolic acid (MPA) on monocyte activation and function. Here, the effect of these immunosuppressants on monocytes was investigated by measuring phosphorylation of three intracellular signaling proteins which all have a major role in monocyte function: p38MAPK, ERK and Akt. In addition, biological functions downstream of these signaling pathways were studied, including cytokine production, phagocytosis and differentiation into macrophages. To this end, blood samples from healthy volunteers were spiked with diverse concentrations of tacrolimus and MPA. Tacrolimus (200 ng/ml) inhibited phosphorylation of p38MAPK by 30% (mean) in CD14+ monocytes which was significantly less than in activated CD3+ T cells (max 60%; p < 0.05). This immunosuppressive agent also partly inhibited p-AKT (14%). MPA, at a therapeutic concentration showed the strongest effect on p-AKT (27% inhibition). p-ERK was inhibited with a maximum of 15% after spiking with either tacrolimus or MPA. The production of IL-1β and phagocytosis by monocytes were not affected by tacrolimus concentrations, whereas MPA did inhibit IL-1β production by 50%. Monocyte/macrophage polarization was shifted to an M2-like phenotype in the presence of tacrolimus, while MPA increased the expression of M2 surface markers, including CD163 and CD200R, on M1 macrophages. These results show that tacrolimus and MPA do not strongly affect monocyte function, apart from a change in macrophage polarization, to a clinically relevant degree. PMID:28122021

  8. Inhibitory effect of ciprofloxacin on β-glucuronidase-mediated deconjugation of mycophenolic acid glucuronide.

    PubMed

    Kodawara, Takaaki; Masuda, Satohiro; Yano, Yoshitaka; Matsubara, Kazuo; Nakamura, Toshiaki; Masada, Mikio

    2014-07-01

    The interaction between mycophenolate (MPA) and quinolone antibiotics such as ciprofloxacin is considered to reduce the enterohepatic recycling of MPA, which is biotransformed in the intestine from MPA glucuronide (MPAG) conjugate excreted via the biliary system; however, the molecular mechanism underlying this biotransformation of MPA is still unclear. In this study, an in vitro system was established to evaluate β-glucuronidase-mediated deconjugation and to examine the influence of ciprofloxacin on the enzymatic deconjugation of MPAG and MPA resynthesis. Resynthesis of MPA via deconjugation of MPAG increased in a time-dependent manner from 5 to 60 min in the presence of β-glucuronidase. Ciprofloxacin and phenolphthalein-β-d-glucuronide (PhePG), a typical β-glucuronidase substrate, significantly decreased the production of MPA from MPAG in the β-glucuronidase-mediated deconjugation system. In addition, enoxacin significantly inhibited the production of MPA from MPAG, while levofloxacin and ofloxacin had no inhibitory effect on MPA synthesis. Pharmacokinetic analysis revealed that ciprofloxacin showed a dose-dependent inhibitory effect on MPA production from MPAG via β-glucuronidase with a half-maximal inhibitory concentration (IC50 ) value of 30.4 µm. While PhePG inhibited the β-glucuronidase-mediated production of MPA from MPAG in a competitive manner, ciprofloxacin inhibited MPA synthesis via noncompetitive inhibition. These findings suggest that the reduction in the serum MPA concentration during the co-administration of ciprofloxacin is at least in part due to the decreased enterohepatic circulation of MPA because of noncompetitive inhibition of deconjugation of MPAG by intestinal β-glucuronidase.

  9. Genetic basis for mycophenolic acid production and strain-dependent production variability in Penicillium roqueforti.

    PubMed

    Gillot, Guillaume; Jany, Jean-Luc; Dominguez-Santos, Rebeca; Poirier, Elisabeth; Debaets, Stella; Hidalgo, Pedro I; Ullán, Ricardo V; Coton, Emmanuel; Coton, Monika

    2017-04-01

    Mycophenolic acid (MPA) is a secondary metabolite produced by various Penicillium species including Penicillium roqueforti. The MPA biosynthetic pathway was recently described in Penicillium brevicompactum. In this study, an in silico analysis of the P. roqueforti FM164 genome sequence localized a 23.5-kb putative MPA gene cluster. The cluster contains seven genes putatively coding seven proteins (MpaA, MpaB, MpaC, MpaDE, MpaF, MpaG, MpaH) and is highly similar (i.e. gene synteny, sequence homology) to the P. brevicompactum cluster. To confirm the involvement of this gene cluster in MPA biosynthesis, gene silencing using RNA interference targeting mpaC, encoding a putative polyketide synthase, was performed in a high MPA-producing P. roqueforti strain (F43-1). In the obtained transformants, decreased MPA production (measured by LC-Q-TOF/MS) was correlated to reduced mpaC gene expression by Q-RT-PCR. In parallel, mycotoxin quantification on multiple P. roqueforti strains suggested strain-dependent MPA-production. Thus, the entire MPA cluster was sequenced for P. roqueforti strains with contrasted MPA production and a 174bp deletion in mpaC was observed in low MPA-producers. PCRs directed towards the deleted region among 55 strains showed an excellent correlation with MPA quantification. Our results indicated the clear involvement of mpaC gene as well as surrounding cluster in P. roqueforti MPA biosynthesis.

  10. Synthesis and biological activity of ester derivatives of mycophenolic acid and acridines/acridones as potential immunosuppressive agents.

    PubMed

    Cholewinski, Grzegorz; Iwaszkiewicz-Grzes, Dorota; Trzonkowski, Piotr; Dzierzbicka, Krystyna

    2016-12-01

    Improved derivatives of mycophenolic acid (MPA) are necessary to reduce the frequency of adverse effects, this drug exerts in treated patients. In this study, MPA was coupled with N-(ω-hydroxyalkyl)-9-acridone-4-carboxamides or N-(ω-hydroxyalkyl)acridine-4-carboxamides to give respective ester conjugates upon Yamaguchi protocol. This esterification required protection of phenol group in MPA. Designed conjugates revealed higher potency in vitro than parent MPA. Acridine derivatives were more active than acridone analogs and length of the alkyl linker between MPA and heterocyclic units influenced the observed cytotoxicity. Derivatives 2b, 2d, 3a, 3b displayed the most promising immunosuppressive activity.

  11. 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

    PubMed Central

    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 <10% in biomarker-led care. The secondary outcomes include the rate of 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

  12. Moving East: the Euro-Lupus Nephritis regimen in Asia.

    PubMed

    Houssiau, Frédéric A

    2016-01-01

    Treatment of lupus nephritis is more evidenced-based than ever. Yet many areas of uncertainty persist. The article by Rathi et al. brings a piece to the puzzle by comparing, in a group of Indian patients, the Euro-Lupus low-dose i.v. cyclophosphamide regimen with mycophenolate mofetil. Although some caveats must be raised, the results suggest that, after crossing the Atlantic, the Euro-Lupus regimen may well be moving East.

  13. [Advances in the knowledge and management of autoimmune lymphoproliferative syndrome].

    PubMed

    Garrido Colino, C

    2014-02-01

    Autoimmune lymphoproliferative syndrome (ALPS) represents a failure of apoptotic mechanisms to maintain lymphocyte homeostasis. ALPS often manifest in childhood with cytopenias, chronic non-malignant lymphoproliferation and autoimmune complications. A number of new insights have improved the understanding of the genetics and biology of ALPS. The treatment of the disease has changed and mycophenolate mofetil and sirolimus have been demonstrated to have marked activity against the disease, improving quality of life for many patients. These will be discussed in this review.

  14. Nonstandard drugs and feasible new interventions for autoimmune hepatitis: part I.

    PubMed

    Czaja, Albert J

    2012-10-01

    Nonstandard drugs that target critical pathogenic pathways or immune regulatory mechanisms constitute the next generation of treatments for autoimmune hepatitis. Mycophenolate mofetil impairs the proliferation of lymphocytes, decreases autoantibody production, and induces apoptosis of activated immunocytes. Patients treated for azathioprine intolerance improve more frequently than patients treated for refractory liver disease (54% versus 10%), and mycophenolate mofetil is emerging as a rescue therapy for this population. Complete corticosteroid withdrawal is possible in 40% of patients treated with mycophenolate mofetil, and the frequency of side effects ranges from 3-34%. Budesonide in combination with azathioprine has normalized liver tests more frequently (47% versus 18%) and with fewer side effects (28% versus 53%) than standard therapy after 6 months. Budesonide is emerging as a frontline treatment in non-cirrhotic patients with uncomplicated disease or contraindications to conventional corticosteroids. Cyclosporine and tacrolimus are effective salvage agents for steroid-refractory disease, but side effects have been common and occasionally serious. The 6- thioguanine nucleotides and rapamycin are feasible treatments for autoimmune hepatitis, but 6-thioguanine has major obstacles to overcome, especially the risk of liver toxicity or nodular regenerative hyperplasia. The nonstandard drug therapies emerging for autoimmune hepatitis reflect the need to supplement or supplant current treatment regimens. None has been licensed for use in autoimmune hepatitis, and their applications have been based on results from small singlecenter experiences.

  15. Effects of Phenylglyoxal and N-ethylmaleimide Concentration on Mycophenolic Acid Production by Penicillium brevi-compactum ATCC16024

    PubMed Central

    Ardestani, Fatemeh

    2016-01-01

    Mycophenolic acid is a secondary extracellular metabolite of Penicillium strains with numerous pharmaceutical properties such as antibiotic and immunosuppressive uses. The aim of this work is the survey of the effect of phenylglyoxal and n-ethylmaleimide concentration in culture medium on mycophenolic acid production by Penicillium brevi-compactum ATCC16024 was investigated. Batch submerged fermentation was performed in 250 mL shake flasks at 24 °C and 200 rpm in a rotary shaker for 300 h using a basic culture medium containing different concentrations of phenylglyoxal and n-ethylmaleimide ranged from 0 to 20 mg. L-1. For the basic medium without any amounts of phenylglyoxal and n-ethylmaleimide (control), maximum MPA production, product yield and productivity of process was in order, 1.5042 g. L-1, 20.3 mg. g-1 consumed glucose and 5.37 mg. L-1h-1. Maximum produced MPA of 2.9032 g. L-1, MPA yield of 39.23 mg. g-1 of consumed glucose, productivity of 10.37 mg. L-1 h-1 and total enhancement of 93.11% was obtained when the culture medium was contained 18 mg. L-1 of phenylglyoxal, represented more than 93% raising in compare to control. Maximum MPA concentration, yield and productivity in order was obtained 3.1123 g. L-1, 42.06 mg. g-1 of consumed glucose and 11.11 mg. L-1 h-1, with using 6 mg. L-1 of n-ethylmaleimide. N-ethylmaleimide was caused to 2.138 folds (106.89%) increase in MPA production by P. brevi-compactum ATCC16024. PMID:28243291

  16. Comparative metabolism of mycophenolic acid by glucuronic acid and glucose conjugation in human, dog, and cat liver microsomes.

    PubMed

    Slovak, J E; Mealey, K; Court, M H

    2017-04-01

    Use of the immunosuppressant mycophenolic acid (MPA) in cats is limited because MPA elimination depends on glucuronidation, which is deficient in cats. We evaluated formation of major (phenol glucuronide) and minor (acyl glucuronide, phenol glucoside, and acyl glucoside) MPA metabolites using liver microsomes from 16 cats, 26 dogs, and 48 humans. All MPA metabolites were formed by human liver microsomes, while dog and cat liver microsomes formed both MPA glucuronides, but only one MPA glucoside (phenol glucoside). Intrinsic clearance (CLint) of MPA for phenol glucuronidation by cat liver microsomes was only 15-17% that of dog and human liver microsomes. However, CLint for acyl glucuronide and phenol glucoside formation in cat liver microsomes was similar to or greater than that for dog and human liver microsomes. While total MPA conjugation CLint was generally similar for cat liver microsomes compared with dog and human liver microsomes, relative contributions of each pathway varied between species with phenol glucuronidation predominating in dog and human liver microsomes and phenol glucosidation predominating in cat liver microsomes. MPA conjugation variation between cat liver microsomes was threefold for total conjugation and for phenol glucosidation, sixfold for phenol glucuronidation, and 11-fold for acyl glucuronidation. Our results indicate that total MPA conjugation is quantitatively similar between liver microsomes from cats, dogs, and humans despite large differences in the conjugation pathways that are utilized by these species.

  17. Change in pharmacokinetics of mycophenolic acid as a function of age in rats and effect of coadministered amoxicillin/clavulanate.

    PubMed

    Ishizaki, Junko; Tsuda, Tomoko; Suga, Yukio; Ito, Satsuki; Arai, Kunizo; Sai, Yoshimichi; Miyamoto, Ken-Ichi

    2012-01-01

    Changes of mycophenolic acid (MPA) pharmacokinetics with aging were investigated in rats. We also compared the effect of concomitant amoxicillin/clavulanate combination (CVA/AMPC) on the pharmacokinetics of MPA in 4-week-old and 12-week-old rats (the package insert of CVA/AMPC warns of possible interaction with MPA). Four-week-old rats showed a 1.4-fold higher total body clearance of MPA and a lower volume of distribution of MPA (65%), compared to the values in 12-week-old rats. However, the difference in MPA pharmacokinetics disappeared when enterohepatic circulation was eliminated by bile duct cannulation (BDC). Concomitant CVA/AMPC significantly reduced plasma MPA concentration in intact rats of both age groups, and the age-dependent difference of MPA pharmacokinetics was no longer apparent. The effect of CVA/AMPC was not seen in rats that had undergone BDC, suggesting that the drug-drug interaction can be attributed to inhibition of enterohepatic circulation by CVA/AMPC. These results indicate that the aging-related alteration of MPA pharmacokinetics is a consequence of immature enterohepatic circulation in 4-week-old rats. Higher doses of MPA may be necessary in juveniles.

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

    PubMed Central

    2011-01-01

    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. PMID:21923907

  19. High prevalence of potential drug interactions affecting mycophenolic acid pharmacokinetics in nonmyeloablative hematopoietic stem cell transplant recipients

    PubMed Central

    Jaklič, Alenka; Collins, Carol J.; Mrhar, Aleš; Sorror, Mohamed L.; Sandmaier, Brenda M.; Bemer, Meagan J.; Locatelli, Igor; McCune, Jeannine S.

    2013-01-01

    Objective: Mycophenolic acid (MPA) exposure is associated with clinical outcomes in hematopoietic cell transplant (HCT) recipients. Various drug interaction studies, predominantly in healthy volunteers or solid organ transplant recipients, have identified medications which impact MPA pharmacokinetics. Recipients of nonmyeloablative HCT, however, have an increased burden of comorbidities, potentially increasing the number of concomitant medications and potential drug interactions (PDI) affecting MPA exposure. Thus, we sought to be the first to characterize these PDI in nonmyeloablative HCT recipients. Materials and methods: We compiled PDI affecting MPA pharmacokinetics and characterized the prevalence of PDI in nonmyeloablative HCT recipients. A comprehensive literature evaluation of four databases and PubMed was conducted to identify medications with PDI affecting MPA pharmacokinetics. Subsequently, a retrospective medication review was conducted to characterize the cumulative PDI burden, defined as the number of PDI for an individual patient over the first 21 days after allogeneic graft infusion, in 84 nonmyeloablative HCT recipients. Results: Of the 187 concomitant medications, 11 (5.9%) had a PDI affecting MPA pharmacokinetics. 87% of 84 patients had one PDI, with a median cumulative PDI burden of 2 (range 0 – 4). The most common PDI, in descending order, were cyclosporine, omeprazole and pantoprazole. Conclusion: Only a minority of medications (5.9%) have a PDI affecting MPA pharmacokinetics. However, the majority of nonmyeloablative HCT recipients had a PDI, with cyclosporine and the proton pump inhibitors being the most common. A better understanding of PDI and their management should lead to safer medication regimens for nonmyeloablative HCT recipients. PMID:23782584

  20. Validation of an LC-MS/MS method for the quantification of mycophenolic acid in human kidney transplant biopsies.

    PubMed

    Md Dom, Zaipul I; Noll, Benjamin D; Coller, Janet K; Somogyi, Andrew A; Russ, Graeme R; Hesselink, Dennis A; van Gelder, Teun; Sallustio, Benedetta C

    2014-01-15

    Mycophenolic acid (MPA) has a low therapeutic index and large inter-individual pharmacokinetic variability necessitating therapeutic drug monitoring to individualise dosing after transplantation. There is an ongoing discrepancy as to whether plasma MPA concentrations sufficiently predict kidney rejection or toxicity and whether immunosuppressant concentrations within the graft tissue may better predict transplant outcomes. The aim of the study was to develop an LC-MS/MS method for the quantification of MPA concentrations in human kidney biopsies taken as part of routine clinical procedures. A total of 4 surplus human kidney biopsies obtained from 4 different kidney transplant recipients were available to use for this study. MPA was also quantified in 2 kidney samples from rats administered MPA to assess tissue extraction reproducibility. Human kidney biopsies and rat kidneys were homogenised mechanically and underwent liquid-liquid extraction before analysis by LC-MS/MS. MPA-free human kidney tissue was used in calibrators and quality control samples. Analyte detection was achieved from multiple reaction monitoring of the ammonium adducts of both MPA (m/z 321.1→207.3) and N-phthaloyl-l-phenylalanine (PPA, internal standard, m/z 296.2→250.2) using positive electrospray ionisation. The method was linear (calibration curves R(2)>0.99, n=10), precise, and accurate with coefficients of variation and bias less than 15%. Extraction efficiencies for MPA and PPA were approximately 97% and 86%, respectively, and matrix effects were minimal. In 4 kidney transplant recipients, tissue MPA concentrations ranged from 1.3 to 7.7ng/mg of tissue, however, the correlation between blood (C0) and tissue MPA concentrations could not be established. The method was successfully applied to the quantification of MPA in human kidney biopsies without the need to alter current clinical protocols.

  1. Outcomes in Ethnic Minority Renal Transplant Recipients Receiving Everolimus versus Mycophenolate: Comparative Risk Assessment Results From a Pooled Analysis

    PubMed Central

    Melancon, Keith; Mulgaonkar, Shamkant P.; Delcoro, Carlos; Wiland, Anne; McCague, Kevin; Shihab, Fuad S.

    2013-01-01

    Background Everolimus (EVR) has demonstrated good efficacy after renal transplantation. Racial disparities in clinical outcomes after de novo renal transplantation are well documented; whether the efficacy of EVR varies based on recipient ethnicity is unknown. We conducted a comparative risk assessment of EVR by ethnicity. Methods Data on 2004 renal transplant recipients from three EVR studies were pooled to identify the impact of ethnicity on efficacy outcomes across EVR dosing groups and control groups. Ethnic groups compared were African Americans, non-U.S. blacks, Asians, Hispanics, and Caucasians. EVR groups received either 1.5 or 3 mg per day, with either standard-dose cyclosporine or reduced-dose cyclosporine. Control groups received mycophenolic acid (MPA) with standard-dose cyclosporine. Composite efficacy failure endpoint was graft loss, death, biopsy-proven acute rejection, or lost to follow-up. Adjusted odds ratios were calculated using a logistic regression model. Results The proportion of renal transplant recipients who met the composite endpoint was African Americans (46%), non-U.S. black (35%), Caucasian (31%), Hispanic (28%), and Asian (25%). The odds of meeting the composite endpoint were significantly (P=0.0001) greater for African Americans versus Caucasians but did not differ among the other ethnic groups (ethnic groups were only compared with Caucasians). EVR and MPA were associated with similar efficacy among each of the ethnic groups. Conclusion In this pooled data analysis in more than 2000 renal transplant recipients, EVR versus MPA resulted in similar composite endpoint incidence events across ethnicities. Consistent with previously published data, African Americans had poorer clinical outcomes. EVR is efficacious regardless of ethnicity. PMID:24345868

  2. Treatment of Cutaneous Lupus

    PubMed Central

    Chang, Aileen Y.; Werth, Victoria P.

    2011-01-01

    Cutaneous lupus erythematosus (CLE) is an autoimmune, inflammatory skin disease seen in patients with or without systemic lupus erythematosus (SLE). The management of CLE includes treatment and prevention of lesions, as well as routine assessment for systemic disease. Treatment options include both topical and systemic therapies. Topical therapies include corticosteroids and calcineurin inhibitors. Systemic therapies generally fall under one of three categories: antimalarials, immunomodulators, such as dapsone and thalidomide, and immunosuppressives, such as methotrexate and mycophenolate. Evidence for the treatment of CLE is limited by few prospective studies, as well as lack of a validated outcome measure up until recently. There is good evidence to support the use of topical steroids and calcineurin inhibitors, though most of these trials have not used placebo or vehicle controls. There have been no randomized placebo-controlled trials evaluating systemic therapies for the treatment of CLE. PMID:21503694

  3. [The role of core decompression for the treatment of femoral head avascular necrosis in renal transplant recipients].

    PubMed

    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

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

    PubMed Central

    Walling, Hobart W; Swick, Brian L

    2010-01-01

    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-α 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. PMID:21437065

  5. Effect of mycophenolic acid on TNFα-induced expression of cell adhesion molecules in human venous endothelial cells in vitro

    PubMed Central

    Hauser, Ingeborg A; Johnson, David R; Thévenod, Frank; Goppelt-Strübe, Margarete

    1997-01-01

    Mycophenolic acid (MPA) is an inhibitor of inosine-5′-monophosphate dehydrogenase and therefore interferes with cellular GTP biosynthesis. Recently, MPA has been used as an antiproliferative and immunosuppressive agent. In the present study, the effect of MPA on the expression of the endothelial cell adhesion molecules (CAMs), intercellular (I) CAM-1, vascular (V) CAM-1 and endothelial (E)-selectin, was investigated in tumour necrosis factor-α (TNFα)-activated cultured human venous endothelial cells (EC).Surface expression of CAMs was measured by flow cytometry and mRNA expression by Northern blot analysis. Transcriptional activation of CAMs by the nuclear factor NF-κB was determined by an electromobility shift assay. The function of CAMs was studied by a static adhesion assay with human monocyte-like undifferentiated U937 cells.Pretreatment of TNFα- (5  ng ml−1, 12 h) activated EC with MPA (10 μM, 24 h) increased the binding of U937 cells, which had not been treated with MPA, by ≈amp;2 fold. MPA-pretreatment of EC did not affect TNFα-induced surface expression of ICAM-1. However, VCAM-1 and E-selectin were increased 2–3 fold and remained elevated up to 24 h, by which time TNFα-activated control EC had returned to baseline levels of expression. The effect of MPA on the surface expression of CAMs was half-maximal at ≈amp;1 μM and required ⩾12 h of pretreatment. Guanosine (0.3 mM), a precursor of GTP, did not prevent the effect of MPA on the expression of CAMs in TNFα-activated EC.Kinetics of mRNA expression of CAMs mirrored protein expression: mRNA for ICAM-1 was unaffected, whereas TNFα-induced mRNA expression for E-selectin and VCAM-1 was prolonged and increased by MPA. This effect was not due to increased transcription mediated by the nuclear transcription factor NF-κB. However, half-life for E-selectin mRNA was increased 10 fold by MPA, whereas ICAM-1 mRNA half-life was unchanged.The data demonstrate that apart from its

  6. Neuromyelitis optica in patients with coexisting human immunodeficiency virus infections.

    PubMed

    Feyissa, Anteneh M; Singh, Parbhdeep; Smith, Robert G

    2013-09-01

    Two patients with known human immunodeficiency virus (HIV) infections and receiving antiretroviral treatment developed neuromyelitis optica (Devic's disease). One patient tested positive for serum aquaporin-4 immunoglobulin G antibodies. Both patients were treated with high dose pulsed intravenous methylprednisolone followed by standard sessions of plasma exchange both at the onset attack and during disease relapses. For maintenance therapy, one patient received rituximab infusions and the second patient received mycophenolate mofetil orally. Despite treatment, both patients are currently wheelchair-bound due to severe paraparesis. Neuromyelitis optica can occur in the course of HIV infection and poses an ongoing therapeutic challenge.

  7. Acute antibody-mediated rejection after ABO-incompatible kidney transplantation treated successfully with antigen-specific immunoadsorption.

    PubMed

    Just, Søren Andreas; Marcussen, Niels; Sprogøe, Ulrik; Koefoed-Nielsen, Pernille; Bistrup, Claus

    2010-01-01

    ABO-incompatible kidney transplantation is possible after pre-treatment with rituximab, intravenous immunoglobulin and basiliximab combined with tacrolimus, mycophenolate mofetil and prednisolone. We report on the first patient treated with this protocol who developed acute antibody-mediated rejection (Banff grade II with IgG deposits) caused by ABO antibodies (anti-B). Anti-rejection treatment with anti-B-specific immunoadsorption, intravenous immunoglobulin and methylprednisolone efficiently cleared deposited IgG from the kidney allograft and re-established normal kidney function. We suggest that ABO-incompatible kidney transplantation complicated by acute antibody-mediated rejection, caused by ABO antibodies, may successfully be treated with this regime.

  8. Neurosarcoidosis

    PubMed Central

    Lacomis, David

    2011-01-01

    Neurosarcoidosis is an uncommon but potentially serious manifestation of sarcoidosis. While the cranial nerves are most frequently affected, neurosarcoidosis can involve other nervous system tissues including the meninges, brain parenchyma (especially the hypothalamic region), spinal cord, peripheral nerve, and muscle. Diagnosis may be particularly challenging when neurosarcoidosis occurs in isolation. Diagnostic criteria usually include histologic identification of a noncaseating granuloma, supportive laboratory or imaging tests or both, and a compatible clinical course. Treatment has not been subjected to rigorous study, but corticosteroids are typically the first line of therapy and approximately half of patients have substantial benefit. For patients who are refractory to or intolerant of corticosteroid therapy, second-line agents include azathioprine, methotrexate, cyclosporine, cyclophosphamide, mycophenolate, and even cranial irradiation. The combination of infliximab and mycophenolate mofetil is under study as well. Treatment options will likely evolve as well-designed studies are undertaken. PMID:22379457

  9. [Treatment with immunosuppressive and biologic drugs of pregnant women with systemic rheumatic or autoimmune disease].

    PubMed

    Alijotas-Reig, Jaume; Esteve-Valverde, Enrique; Ferrer-Oliveras, Raquel

    2016-10-21

    Rheumatic and systemic autoimmune diseases occur in women and, to a lesser degree, men of reproductive age. These disorders have to be clinically nonactive before conception, which is usually only possible after anti-inflammatory and immunosuppressive treatment. We must be alert since 50% of pregnancies are unplanned. Physicians should know the embryo-foetal toxicity of these drugs during pregnancy and lactation. This January 2016-updated review allows us to conclude that the majority of immunosuppressives available -anti-TNF inhibitors included- can be used before and during pregnancy, with the exception of cyclophosphamide, methotrexate, mycophenolate and leflunomide. Lactation is permitted with all drugs except methotrexate, leflunomide, mycophenolate and cyclophosphamide. Although data on abatacept, belimumab, rituximab, tocilizumab and anakinra are scant, preliminary reports agree on their safety during pregnancy and, probably, lactation. Cyclophosphamide and sulfasalazine apart, no negative effects on sperm quality, or embryo-foetal anomalies in men treated with immunosuppressives have been described.

  10. Do we still need renal biopsy in lupus nephritis?

    PubMed

    Haładyj, Ewa; Cervera, Ricard

    2016-01-01

    The natural course of systemic lupus erythematosus (SLE) is characterized by periods of disease activity and remissions. Prolonged disease activity results in cumulative organ damage. Lupus nephritis is one of the most common and devastating manifestations of SLE. In the era of changing therapy to less toxic regimens, some authors have stated that if mycophenolate mofetil can be used for the induction and maintenance treatment in all histological classes of lupus nephritis, renal biopsy can be omitted. This article aims to answer the question of what brings the bigger risk: renal biopsy or its abandonment.

  11. Type 4 renal tubular acidosis in a kidney transplant recipient.

    PubMed

    Kulkarni, Manjunath

    2016-02-01

    We report a case of a 66-year-old diabetic patient who presented with muscle weakness 2 weeks after kidney transplantation. Her immunosuppressive regimen included tacrolimus, mycophenolate mofetil, and steroids. She was found to have hyperkalemia and normal anion gap metabolic acidosis. Tacrolimus levels were in therapeutic range. All other drugs such as beta blockers and trimethoprim - sulfamethoxazole were stopped. She did not respond to routine antikalemic measures. Further evaluation revealed type 4 renal tubular acidosis. Serum potassium levels returned to normal after starting sodium bicarbonate and fludrocortisone therapy. Though hyperkalemia is common in kidney transplant recipients, determining exact cause can guide specific treatment.

  12. Superior Orbital Fissure Syndrome and Ophthalmoplegia Caused by Varicella Zoster Virus with No Skin Eruption in a Patient Treated with Tumor Necrosis Alpha Inhibitor

    PubMed Central

    Jensen, Helene; Thomsen, Sidsel Thorup; Hansen, Stine Scott; Munksgaard, Signe Bruun; Lindelof, Mette

    2015-01-01

    Varicella zoster virus lies dormant in the dorsal root ganglia after symptomatic chicken pox infection, usually in childhood. If the virus reactivates in the trigeminal ganglia, it can cause varicella zoster ophthalmicus, which can have severe ocular complications. We report a case of a 73-year-old woman in severe immunosuppression due to treatment with mycophenolate mofetil, glucocorticosteroids and a tumor necrosis factor alpha inhibitor. The reactivation caused superior orbital fissure syndrome, which has only rarely been described in relation to varicella zoster virus reactivation. In our case, the syndrome was seen along with severe encephalitis. PMID:26600786

  13. Novel approaches to therapy for systemic lupus erythematosus: update 2005.

    PubMed

    Zandman-Goddard, Gisele; Orbach, Hedi; Shoenfeld, Yehuda

    2005-07-01

    This review covers the major advances in the therapeutic potentials related to systemic lupus erythematosus published in Medline between 2000 and February 2005. Controlled, open and Phase I-III trials were included. Anecdotal reports were excluded. Several trials have defined the role of cyclophosphamide, methotrexate, antimalarials, hormonal treatment and mycophenolate mofetil (Cellcept) in the management of systemic lupus erythematosus. The aims of novel biologics for systemic lupus erythematosus are to target the autoimmune disease at different points: B-cell depletion (rituximab [Rituxan], anti-BLys antibodies [Lymphostat-B]), inhibition of T-B interaction (rituximab), blockade of cytokines (anti-interleukin-10 antibodies), manipulation of idiotypes (intravenous immunoglobulin), tolerance induction to DNA and immunoglobulin-peptides and peptide therapy (abetimus sodium [Riquent]). Low-dose intravenous cyclophosphamide (Euro-Lupus protocol) is as effective as the conventional National Institutes of Health protocol and is also associated with less toxicity. Stem cell transplantation for severe disease induces remission in most patients, however, the relapse rate in a third of patients and the associated morbity and mortality restricts its use to selected patients with life-threatening disease. Intravenous immunoglobulin, although utilized in open trials, is effective and safe for various manifestations of systemic lupus erythematosus. Major advances have been associated with mycophenolate mofetil and rituximab. Mycophenolate mofetil is effective for induction and maintenance therapy of lupus proliferative glomerulonephritis and is associated with fewer adverse events than monthly intravenous cyclophosphamide. Rituximab is a promising agent, and although its utilization is presently limited, it appears to be effective for lupus patients with severe disease.

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

    PubMed

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

    2017-02-15

    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 <7% and biases <10%. The freeze-dried samples were stable at ambient temperature for at least 40 days. This method was also successfully applied to the pharmacokinetic study of MPA in healthy volunteers. Pharmacokinetic parameters, such as maximum 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.

  15. Pharmacokinetics and pharmacodynamics of mycophenolic acid in Nagase analbuminemic rats: Evaluation of protein binding effects using the modeling and simulation approach.

    PubMed

    Yoshimura, Kazuaki; Yano, Ikuko; Kawanishi, Misaki; Nakagawa, Shunsaku; Yonezawa, Atsushi; Matsubara, Kazuo

    2015-12-01

    This study aimed to examine the pharmacokinetics and pharmacodynamics of mycophenolic acid (MPA) in Nagase analbuminemic rats (NARs) to evaluate the effect of protein binding on the associated inosine-5'-monophosphate dehydrogenase (IMPDH) activity. Free fractions of MPA in the control rats and NARs were 2.09 and 24.8%, respectively. Pharmacokinetic and pharmacodynamic parameters simultaneously obtained by the nonlinear mixed effects modeling program NONMEM explained reasonably well the concentrations of MPA and MPA glucuronide as well as IMPDH activity in both rats. NARs showed a higher clearance and a smaller volume of distribution based on the free MPA concentration than the controls did, besides the increase in free fraction. The half-maximal inhibitory concentration based on free MPA was estimated as 163 ng/mL for both rats. Simulations based on the obtained pharmacokinetic and pharmacodynamic parameters showed that the area under the IMPDH activity-time curve decreased non-linearly according to the increase in free fraction of MPA. In conclusion, the experimental data obtained from NARs followed by the modeling and simulation approach quantitatively clarified that the free MPA concentration was suitable for the biomarker of immunosuppressive effect of MPA. Dose adjustments based on the total MPA may cause unnecessary overexposure to MPA in patients with hypoalbuminemia.

  16. Pilot conversion trial from mycophenolic acid to everolimus in ABO-incompatible kidney-transplant recipients with BK viruria and/or viremia.

    PubMed

    Belliere, Julie; Kamar, Nassim; Mengelle, Catherine; Allal, Asma; Sallusto, Federico; Doumerc, Nicolas; Game, Xavier; Congy-Jolivet, Nicolas; Esposito, Laure; Debiol, Benedicte; Rostaing, Lionel

    2016-03-01

    Immunosuppression using everolimus (EVR) plus low-dose tacrolimus (Tac) is commonly used in organ transplantation. EVR has potential antiviral effects. Herein, the long-term outcomes and impacts of Tac-EVR on the BK virus are reported in ABO-incompatible kidney-transplant recipients. The initial immunosuppressive regimen combined steroids, Tac, and mycophenolic acid (MPA). At a median of 141 (34-529) days post-transplantation, seven stable ABO-incompatible kidney-transplant recipients were converted from MPA to EVR because of active BK replication, and compared with a reference group of fourteen ABO-incompatible patients receiving classical Tac plus MPA. At 1 month before conversion, at 1, 3 months after, and at last follow-up, clinical and biological parameters were monitored. The median time from conversion to the last follow-up was 784 (398-866) days. Conversion to EVR caused no change to rejection episodes or immunological status (isoagglutinin titers, anti-HLA antibodies). At last follow-up, median eGFR was similar in the Tac-MPA versus Tac-EVR group (40 [range: 14-56] vs. 54.5 ml/min/1.73 m(2) [range: 0-128], P = 0.07). The major adverse event was dyslipidemia. Interestingly, conversion from MPA to EVR decreased BK viral load in five patients. ABO-incompatible kidney-transplant recipients with an active BK virus infection may benefit from conversion to EVR.

  17. Treatment

    MedlinePlus

    ... Ban For Clinicians Clinical Recognition Specimen Collection Treatment Smallpox Vaccine Guidance Infection Control: Hospital Infection Control: Home ... Mouth Infection) Poxvirus and Rabies Branch Travelers’ Health: Smallpox & Other Orthopoxvirus-Associated Infections Poxvirus Treatment Recommend on ...

  18. Lupus vasculopathy: Diagnostic, pathogenetic and therapeutic considerations.

    PubMed

    Gonzalez-Suarez, M L; Waheed, A A; Andrews, D M; Ascherman, D P; Zeng, X; Nayer, A

    2014-04-01

    A rare form of vascular disease in systemic lupus erythematosus (SLE), lupus vasculopathy is characterized by necrosis and accumulation of immunoglobulins (IGs) and complements in the wall of arterioles and small arteries resulting in luminal narrowing. Lupus vasculopathy often accompanies lupus nephritis and portends a poor prognosis. Although there is general agreement on the treatment of lupus nephritis, effective treatment strategies for lupus vasculopathy remain to be defined. We report a 20-year-old woman with SLE who presented with generalized tonic-clonic seizure. Her immunosuppressive regimen consisted of mycophenolate mofetil, prednisone and hydroxychloroquine. On physical examination, she was Cushingoid in appearance and hypertensive. Laboratory tests indicated renal disease. Coagulation studies disclosed de novo lupus anticoagulant. Magnetic resonance imaging of the brain demonstrated acute focal cerebral hemorrhage. Echocardiography revealed reduced ejection fraction and severe mitral regurgitation. Despite high-dose glucocorticoids and mycophenolate mofetil, renal function remained poor. Kidney biopsy demonstrated lupus vasculopathy and glomerulonephritis. Plasma exchange therapy and intravenous cyclophosphamide were administered. Over the ensuing four weeks, renal function improved, complement levels increased, autoantibody titers decreased and lupus anticoagulant disappeared. In conclusion, lupus vasculopathy can occur in SLE despite a heavy immunosuppressive regimen. Antiphospholipid antibodies might be involved in the pathogenesis of lupus vasculopathy. Plasma exchange therapy in conjunction with intravenous cyclophosphamide may represent an effective treatment strategy for lupus vasculopathy.

  19. Pro: The use of calcineurin inhibitors in the treatment of lupus nephritis.

    PubMed

    Mok, Chi Chiu

    2016-10-01

    Renal disease in systemic lupus erythematosus (SLE) carries significant morbidity and mortality. Cyclophosphamide (CYC)- and mycophenolate mofetil (MMF)-based induction regimens are not ideal in terms of efficacy and toxicity. The adverse effects of CYC, such as infection risk, infertility, urotoxicity and oncogenicity, limit its use in lupus nephritis. Although MMF is non-inferior to CYC as induction therapy and has reduced gonadal toxicity and oncogenic potential, meta-analyses of clinical trials do not show a lower rate of infective and gastrointestinal complications. Tacrolimus (TAC) has recently been shown to have equal efficacy to either MMF or CYC for inducing remission of lupus nephritis. A low-dose combination of MMF and TAC appears to be more effective than intravenous CYC pulses in Chinese patients, and has potential to replace the more toxic CYC regimens in high-risk subgroups. TAC may be considered as another non-CYC alternative for induction therapy of lupus nephritis and in those with refractory disease or intolerance to CYC or MMF. TAC has no negative effect on fertility in younger women, and unlike MMF and CYC, it is safe in pregnancy. However, TAC has a narrow therapeutic window and drug level monitoring is required to ensure drug exposure and minimize acute toxicities. Current evidence for the efficacy of TAC in lupus nephritis is limited to 6 months and the incidence of renal flare after discontinuation of therapy or switching to azathioprine appears to be higher than other induction agents. Long-term data and the incidence of chronic nephrotoxicity of TAC as maintenance therapy in lupus nephritis are currently lacking and further prospective trials are needed to address these issues.

  20. Simple and Sensitive High-Performance Liquid Chromatography (HPLC) Method with UV Detection for Mycophenolic Acid Assay in Human Plasma. Application to a Bioequivalence Study

    PubMed Central

    Danafar, Hossein; Hamidi, Mehrdad

    2015-01-01

    Purpose: A simple and available reversed-phase high performance liquid chromatography (HPLC) method with UV detection has been developed and validated for mycophenolic acid (MPA) assay in human plasma. Methods: MPA was extracted from plasma with protein precipitation method by acetonitrile: percholeric acid: methanol (75:5:20 v/v/v). The drug separation was achieved using a C8 analytical column and a mobile phase of 0.1M triethylammonium phosphate (pH=5.4)-acetonitril (65:35, v/v), with a flow rate of 1.5 ml/min. The detection wavelength was 304 nm. Limit of detection (LOD) of the method was determined as the lowest MPA concentration producing a signal-to-noise (S/N) ratio of about 3. Limit of quantitation (LOQ) was determined as the lowest MPA concentration capable of being quantitated with enough accuracy and precision. Results: The method showed significant linear response-concentration relationship throughout the MPA concentration range of 0.2-10 µg/ml. A typical linear regression equation of the method was: y = 8.5523 x + 0.094, with x and y representing MPA concentration (in µg/ml) and peak height respectively, and the regression coefficient (r) of 0.9816. The average within-run and between-run variations of 7.81 and 4.78 percent. The average drug recovery from plasma was 95.24 percent throughout the linear concentration range. The limits of detection (LOD) and quantitation (LOQ) of the method were 0.05 and 0.2 µg/ml, respectively. The practical applicability of the method was proven throughout a bioequivalence study. Conclusion: The results showed the acceptable degree of linearity, sensitivity, precision, accuracy and recovery for the method. The method was used successfully for quantitation of MPA in plasma samples of healthy volunteers throughout a bioequivalence study. PMID:26819930

  1. Mycophenolate-based graft versus host disease prophylaxis is not inferior to methotrexate in myeloablative-related donor stem cell transplantation.

    PubMed

    Hamad, Nada; Shanavas, Mohamed; Michelis, Fotios V; Uhm, Jieun; Gupta, Vikas; Seftel, Matthew; Kuruvilla, John; Lipton, Jeffrey H; Messner, Hans A; Kim, Dennis Dong Hwan

    2015-05-01

    We retrospectively reviewed 242 patients who received related donor myeloablative peripheral blood hematopoietic cell transplantation. We compared patients who received mycophenolate (MMF)/cyclosporine (CSA) (n = 71), to historical controls who received methotrexate (MTX)/CSA (n = 172). There were no differences in overall survival, nonrelapse mortality, and relapse. The MMF/CSA group had significantly faster neutrophil and platelet engraftment: medians of 13 versus 18 days and 10 versus 14 days, respectively (P = 0.001). The cumulative incidence of acute graft versus host disease (GVHD) (Grades, 2-4) was significantly lower in the MMF/CSA group (45.1 vs. 74.4%, P < 0.001). The MMF/CSA group showed a lower incidence of skin (51.5 vs. 72.1%, P < 0.001) and liver acute GVHD (11.3 vs. 54.2%, P < 0.001) and a higher incidence of lung (42.2 vs. 19.0%, P = 0.045), eye (59.7 vs. 30.1%, P < 0.001), and mouth (72.8 vs. 56.4%, P = 0.001) chronic GVHD but only eye chronic GVHD was confirmed in propensity score matching (PSM) analysis. The incidence of cytomegalovirus (CMV) viremia was higher in the MMF/CSA group (55.8 vs. 39.6%, P < 0.001) but this was not confirmed in PSM analysis. MMF/CSA was identified as an independent favorable factor for acute GVHD (P < 0.001, hazard ratio, 0.41) but as a possible adverse risk factor for CMV viremia as this was not found to be statistically significant in PSM analysis. MMF/CSA in myeloablative matched related donor peripheral blood stem cell transplant is not inferior as GVHD prophylaxis in comparison with MTX/CSA and is associated with faster engraftment but a potentially higher risk of CMV viremia.

  2. Effect of Immunosuppressive Therapy on Proteinogram in Rats

    PubMed Central

    Kędzierska, Karolina; Sindrewicz, Krzysztof; Sporniak-Tutak, Katarzyna; Bober, Joanna; Stańczyk-Dunaj, Małgorzata; Dołęgowska, Barbara; Kaliszczak, Robert; Sieńko, Jerzy; Kabat-Koperska, Joanna; Gołembiewska, Edyta; Ciechanowski, Kazimierz

    2016-01-01

    Background It has been observed that the use of immunosuppressive drugs in patients after transplantation of vascularized organs may be associated with changes in the concentration of certain fractions of plasma proteins. The concentration of these proteins was correlated with an increased risk of occurrence of stage 3 chronic kidney disease (CKD). This article examines the effect of the most commonly used immunosuppressive drugs on the concentration of plasma proteins in Wistar rats. Material/methods The study involved 36 rats grouped according to the immunosuppressive regimen used (tacrolimus, mycophenolate mofetil, cyclosporine A, rapamycin, and prednisone). The rats in all study groups were treated with a 3-drug protocol for 6 months. The treatment dose was adjusted based on available data in the literature. No drugs were administered to the control group. The rats were sacrificed and blood samples collected to determine the concentration of plasma proteins using electrophoresis technique. Results Statistically significant differences were observed between protein concentrations within the studied groups. The differences related to the proteins with masses of 195 kDa, 170 kDa, 103 kDa, and 58 kDa. Conclusions (1) Immunosuppressive drugs caused changes in the proteinogram of plasma proteins. (2) The strongest effect on rat plasma proteins was exerted by a regimen based on rapamycin. Intermediate, weak, and weakest effects were observed in regimens based on cyclosporine A, tacrolimus, and mycophenolate mofetil, respectively. PMID:27288069

  3. Mycophenolic acid induces ATP-binding cassette transporter A1 (ABCA1) expression through the PPAR{gamma}-LXR{alpha}-ABCA1 pathway

    SciTech Connect

    Xu, Yanni; Lai, Fangfang; Xu, Yang; Wu, Yexiang; Liu, Qi; Li, Ni; Wei, Yuzhen; Feng, Tingting; Zheng, Zhihui; Jiang, Wei; Yu, Liyan; Hong, Bin; Si, Shuyi

    2011-11-04

    Highlights: Black-Right-Pointing-Pointer Using an ABCA1p-LUC HepG2 cell line, we found that MPA upregulated ABCA1 expression. Black-Right-Pointing-Pointer MPA induced ABCA1 and LXR{alpha} protein expression in HepG2 cells. Black-Right-Pointing-Pointer PPAR{gamma} antagonist GW9662 markedly inhibited MPA-induced ABCA1 and LXR{alpha} protein expression. Black-Right-Pointing-Pointer The effect of MPA upregulating ABCA1 was due mainly to activation of the PPAR{gamma}-LXR{alpha}-ABCA1 pathway. -- Abstract: ATP-binding cassette transporter A1 (ABCA1) promotes cholesterol and phospholipid efflux from cells to lipid-poor apolipoprotein A-I and plays an important role in atherosclerosis. In a previous study, we developed a high-throughput screening method using an ABCA1p-LUC HepG2 cell line to find upregulators of ABCA1. Using this method in the present study, we found that mycophenolic acid (MPA) upregulated ABCA1 expression (EC50 = 0.09 {mu}M). MPA upregulation of ABCA1 expression was confirmed by real-time quantitative reverse transcription-PCR and Western blot analysis in HepG2 cells. Previous work has indicated that MPA is a potent agonist of peroxisome proliferator-activated receptor gamma (PPAR{gamma}; EC50 = 5.2-9.3 {mu}M). Liver X receptor {alpha} (LXR{alpha}) is a target gene of PPAR{gamma} and may directly regulate ABCA1 expression. Western blot analysis showed that MPA induced LXR{alpha} protein expression in HepG2 cells. Addition of PPAR{gamma} antagonist GW9662 markedly inhibited MPA-induced ABCA1 and LXR{alpha} protein expression. These data suggest that MPA increased ABCA1 expression mainly through activation of PPAR{gamma}. Thus, the effects of MPA on upregulation of ABCA1 expression were due mainly to activation of the PPAR{gamma}-LXR{alpha}-ABCA1 signaling pathway. This is the first report that the antiatherosclerosis activity of MPA is due to this mechanism.

  4. Treatment of Rapidly Progressive Systemic Sclerosis: Current and Futures Perspectives

    PubMed Central

    Mendoza, Fabian A.; Mansoor, Maryah; Jimenez, Sergio A.

    2016-01-01

    Introduction Systemic Sclerosis (SSc) is a systemic autoimmune disease characterized by severe and often progressive cutaneous, pulmonary, cardiac and gastrointestinal tract fibrosis, cellular and humoral immunologic alterations, and pronounced fibroproliferative vasculopathy. There is no effective SSc disease modifying therapy. Patients with rapidly progressive SSc have poor prognosis with frequent disability and very high mortality. Areas Covered This paper reviews currently available therapeutic approaches for rapidly progressive SSc and discuss novel drugs under study for SSc disease modification. Expert Opinion The extent, severity, and rate of progression of SSc skin and internal organ involvement determines the optimal therapeutic interventions for SSc. Cyclophosphamide for progressive SSc-associated interstitial lung disease and mycophenolate for rapidly progressive cutaneous involvement have shown effectiveness. Methotrexate has been used for less severe skin progression and for patients unable to tolerate mycophenolate. Rituximab was shown to induce improvement in SSc-cutaneous and lung involvement. Autologous bone marrow transplantation is reserved for selected cases in whom poor survival risk outweighs the high mortality rate of the procedure. Novel agents capable of modulating fibrotic and inflammatory pathways involved in SSc pathogenesis, including tocilizumab, pirfenidone, tyrosine kinase inhibitors, lipid lysophosphatidic acid 1, and NOX4 inhibitors are currently under development for the treatment of rapidly progressive SSc. PMID:27812432

  5. Management of pemphigus vulgaris: challenges and solutions

    PubMed Central

    Gregoriou, Stamatis; Efthymiou, Ourania; Stefanaki, Christina; Rigopoulos, Dimitris

    2015-01-01

    The main objective in the treatment of pemphigus vulgaris is to control the disease, prevent relapses, and avoid adverse events associated with the prolonged use of steroids and immunosuppressive agents. Systemic corticosteroids remain the gold standard treatment for pemphigus vulgaris. Azathioprine and mycophenolate mofetil are the first line of steroid-sparing treatment. Rituximab is extremely effective in recalcitrant pemphigus, when other treatments fail to control the disease. The European Dermatology Forum recommends tapering prednisolone by 25% every 2 weeks after the consolidation phase, and a 5 mg reduction every 4 weeks when the dose is reduced to <20 mg. If the patient relapses, options include increasing steroids back to the previous dose, adding an immunosuppressant if using steroid monotherapy, or replacing a first-line immunosuppressant by another if already on combination therapy. PMID:26543381

  6. The use of immunosuppression in autoimmune hepatitis: A current literature review

    PubMed Central

    Cropley, Angela; Weltman, Martin

    2017-01-01

    Autoimmune hepatitis (AIH) is an organ specific autoimmune condition which can manifest at any age of life. The heterogeneous nature of this condition means that great variation can be seen in severity, progression of disease and response to treatment within this patient group. Since the 1980s prednisolone and azathioprine have been used for induction and remission of the disease and remain the mainstay of treatment. Other immunosuppressive agents have been employed in difficult to treat cases. While there is less published data regarding these agents compared with the conventional treatments of steroid and azathioprine, there is mounting evidence to support the use of mycophenolate mofetil as a second-line agent. The calcineurin inhibitors, though less studied, additionally show promise. More data is needed on the use of biological agents in refractory disease. This review focuses on our centre’s approach to treatment of AIH in the context of a contemporary review of the literature. PMID:28288505

  7. Treatment of early diffuse systemic sclerosis skin disease.

    PubMed

    Frech, Tracy M; Shanmugam, Victoria K; Shah, Ami A; Assassi, Shervin; Gordon, Jessica K; Hant, Faye N; Hinchcliff, Monique E; Steen, Virginia; Khanna, Dinesh; Kayser, Cristiane; Domsic, Robyn T

    2013-01-01

    Diffuse systemic sclerosis carries a high morbidity and mortality. The Prospective Registry of Early Systemic Sclerosis (PRESS), a multicentre incident cohort study of patients with early diffuse cutaneous systemic sclerosis, has the goal of advancing the understanding of disease pathogenesis and identifying novel biomarkers. In this review, PRESS investigators discuss the evidence pertaining to the more commonly used treatments for early diffuse SSc skin disease including methotrexate, mycophenolate, cyclophosphamide, azathioprine, and intravenous immunoglobulin. This review highlights the unmet need for effective treatment in early diffuse SSc as well as its more rigorous study. Nonetheless, the PRESS investigators aim to decrease intra- and inter-institutional variability in prescribing in order to improve the understanding of the clinical course of early diffuse SSc skin disease.

  8. Therapeutic options in autoimmune myasthenia gravis.

    PubMed

    García-Carrasco, Mario; Escárcega, Ricardo O; Fuentes-Alexandro, Salvador; Riebeling, Carlos; Cervera, Ricard

    2007-06-01

    Autoimmune myasthenia gravis (MG) is associated with circulating antibodies to AChR, modification of the synaptic cleft, and destruction of the postsynaptic neuromuscular membrane. The hallmark is fluctuating muscular weakness and fatigability of muscles on sustained repeated activity. Various drugs and invasive procedures have been used in the treatment of MG including acetylcholinesterase inhibitors, corticosteroids, azathioprine, cyclosporine, cyclophosphamide, mycophenolate mofetil, tacrolimus, etanercept, intravenous immunoglobulin, plasma exchange and thymectomy. We review the role of each of these drugs and invasive procedures in MG. Although current treatment is highly successful and mortality is almost nil, further trials are required to identify the most suitable treatments for different subgroups of MG patients. In addition, safer and more potent drugs are required as most current drugs have major side effects due to immunosuppression. Therefore, the goal of novel therapies should be increased specificity of the immune-directed agents.

  9. Update on autoimmune hepatitis

    PubMed Central

    Teufel, Andreas; Galle, Peter R; Kanzler, Stephan

    2009-01-01

    Autoimmune hepatitis (AIH) is a necroinflammatory liver disease of unknown etiology that occurs in children and adults of all ages. Characteristics are its autoimmune features, hyperglobulinemia (IgG), and the presence of circulating autoantibodies, as well as a response to immunosuppressant drugs. Current treatment consists of prednisone and azathioprine and in most patients this disease has become very treatable. Over the past 2 years, a couple of new insights into the genetic aspects, clinical course and treatment of AIH have been reported, which will be the focus of this review. In particular, we concentrate on genome-wide microsatellite analysis, a novel mouse model of AIH, the evaluation of a large AIH cohort for overlap syndromes, suggested novel criteria for the diagnosis of AIH, and the latest studies on treatment of AIH with budenoside and mycophenolate mofetil. PMID:19266594

  10. Optimal Management of Autoimmune Lymphoproliferative Syndrome in Children.

    PubMed

    George, Lindsey A; Teachey, David T

    2016-08-01

    Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of abnormal lymphocyte homeostasis, resulting from mutations in the Fas apoptotic pathway. Clinical manifestations include noninfectious and nonmalignant lymphadenopathy, splenomegaly, and autoimmune pathology-most commonly, autoimmune cytopenias. Rarely, and in association with specific genetic mutations, patients with ALPS may go on to develop secondary lymphoid malignancies. Though ALPS is a rare disorder, it should be suspected and ruled out in children presenting with chronic and refractory multilineage cytopenias associated with nonmalignant lymphoproliferation. Revised diagnostic criteria and insights into disease biology have improved both diagnosis and treatment. Sirolimus and mycophenolate mofetil are the best-studied and most effective corticosteroid-sparing therapies for ALPS, and they should be considered first-line therapy for patients who need chronic treatment. This review highlights practical clinical considerations for diagnosis and management of ALPS.

  11. Immunotherapy of systemic sclerosis

    PubMed Central

    Manno, Rebecca; Boin, Francesco

    2011-01-01

    Scleroderma is a multisystem autoimmune disease characterized by an abnormal immune activation associated with the development of underlying vascular and fibrotic disease manifestations. This article highlights the current use of drugs targeting the immune system in scleroderma. Nonselective immunosuppression, and in particular cyclophosphamide, remains the main treatment for progressing skin involvement and active interstitial lung disease. Mycophenolate mofetil is a promising alternative to cyclophosphamide. The use of cyclosporine has been limited by modest efficacy and serious renal toxicity. Newer T-cell (sirolimus and alefacept) and B-cell (rituximab)-targeted therapies have provided some encouraging results in small pilot studies. Hematopoietic stem cell transplantation can be effective for severe fibrotic skin disease, but toxicity remains a concern. Clinical efficacy and safety of antifibrotic treatments (e.g., imatinib) await confirmation. Newer biological agents targeting key molecular or cellular effectors in scleroderma pathogenesis are now available for clinical testing. PMID:21091117

  12. Repeated CMV Infection in a Heart Transplantation Patient

    PubMed Central

    Melero-Ferrer, Josep; Sanchez-Lazaro, Ignacio J.; Navea-Tejerina, Amparo; Almenar-Bonet, Luis; Blanes-Julia, Marino; Martinez-Dolz, Luis; Salvador-Sanz, Antonio

    2012-01-01

    Infections are one of the leading causes of morbidity and mortality in heart transplantation (HTx). Cytomegalovirus (CMV) is the most common viral infection during the first year after HTx, but it is more unusual after this time. We present the case of a patient who underwent an HTx due to a severe ischemic heart disease. Although the patient did not have a high risk for CMV, infection, he suffered a reactivation during the first year and then up to six more episodes, especially in his eyes. The patient received different treatments against CMV and the immunosuppression was changed several times. Finally, everolimus was introduced instead of cyclosporine, and mycophenolate mofetil was withdrawn. The presented case provides an example of how the immunosupresion plays a key role in some infections in spite of being a suitable antiviral treatment. PMID:23213610

  13. Novel therapeutic agents for systemic lupus erythematosus.

    PubMed

    Gescuk, Bryan D; Davis, John C

    2002-09-01

    The last significant breakthrough in the treatment of systemic lupus erythematosus (SLE) was the use of cyclophosphamide and methylprednisolone in the treatment of lupus nephritis. Recent advances in immunology, oncology, and endocrinology have resulted in many potential therapies for SLE. These therapies include new immunosuppressants, biologic medications, tolerizing agents, immunoablation techniques, and hormonal medications. Each of these approaches will be discussed in this review. Some therapies are currently in use in clinical rheumatology practice (mycophenolate mofetil) and others are entering phase I trials (anti-BLyS monoclonal antibody). While some of these new therapies target specific inflammatory mechanisms in SLE (anti-CD40L monoclonal antibody), others work by nonspecific inhibition of the immune system (immunoablation).

  14. Therapy of lupus nephritis: lessons learned from clinical research and daily care of patients

    PubMed Central

    2012-01-01

    Despite numerous randomized clinical trials over the last three decades for identifying the optimal treatment option for lupus nephritis, renal involvement still significantly impacts the survival and quality of life of patients with lupus and the search for the ideal immunosuppressive regimen is far from complete. The purpose of this review is to summarize the major recent achievements in the field. More specifically, the following topics will be discussed: intravenous cyclophosphamide versus mycophenolate mofetil (MMF) for induction; azathioprine versus MMF for maintenance; targeted therapies. The review will address clues for optimal global care, such as the need for complete initial evaluation, the importance of patient education, the unmasking of non-compliance to therapy, the reason for an early treatment switch in non-responding patients, the need for prolonged immunosuppression, optimal renal protection, and prevention of cardiovascular disease and other comorbidities. PMID:22293173

  15. MMF and eye disease.

    PubMed

    Zierhut, M; Stübiger, N; Siepmann, K; Deuter, C M E

    2005-01-01

    Immunosuppressive treatment has shown to be effective in various ocular inflammatory disorders. Factors limiting their use are the individual response and the rate of side effects. This report summarizes our knowledge about the use of mycophenolate mofetil (MMF) in the treatment of ocular cicatricial pemphigoid (OCP), uveitis, atopic keratoconjunctivitis (AKC), prevention of graft rejection after penetrating keratoplasty (PK) and scleritis. Controlled studies have been performed for prevention of graft rejection after PK, showing MMF as effective in the prevention of graft rejection as cyclosporine A. In experimental uveitis, MMF has been demonstrated to be highly effective in prevention of retinal destruction. A number of studies have now shown that MMF also seems effective in uveitis. There are also studies with smaller patient groups which point out the effectiveness of MMF in OCP, AKC, and scleritis. In most of the studies, the spectrum of side effects was small, compared to other immunosuppressives.

  16. Systemic lupus erythematosus--2005 annus mirabilis?

    PubMed

    Isenberg, David; Rahman, Anisur

    2006-03-01

    We are about to enter a new era in the treatment of patients with systemic lupus erythematosus (SLE). For the past 40 years hydroxychloroquine sulfate and corticosteroids, together with varying combinations of immunosuppressive drugs, have been the main treatments for SLE. Although effective for many patients, some patients fail to respond to these drugs and even more suffer from major side effects due to the generalized nature of the immunosuppression. In this article we review the remarkable confluence of new therapies ranging from newer immunosuppressive drugs with fewer side effects, such as mycophenolate mofetil, to the more targeted approaches offered by biological agents. These agents have been designed to block molecules such as CD20, CD22 and interleukin-10 that are thought to have an integral part in the development of SLE. This wolf might not yet be about to become extinct but its survival is increasingly under threat!

  17. Sjögren Sensory Neuronopathy (Sjögren Ganglionopathy)

    PubMed Central

    Pereira, P. Ricardo; Viala, Karine; Maisonobe, Thierry; Haroche, Julien; Mathian, Alexis; Hié, Miguel; Amoura, Zahir; Cohen Aubart, Fleur

    2016-01-01

    Abstract Primary Sjögren syndrome (SS) is an autoimmune disease mainly affecting the exocrine glands causing a sicca syndrome. Neurological manifestations are rarely seen in SS although they are debilitating. Peripheral neuropathies namely sensory axonal neuropathy and painful small fiber neuropathy are the most frequent neurological manifestations. Sensory neuronopathy (SN) is less frequently seen although leading to more severe handicap. The aim of the study was to analyze the clinical presentation and treatment efficacy in a series of SS-related SN. We retrospectively studied patients with SS fulfilling the American–European Classification Criteria and SN according to recent criteria. Studied variables were neurological findings, associated autoimmune diseases, biological profiles, nerve conduction and sensory/motor amplitudes study, treatments received, and outcomes. Handicap scores were studied at beginning and end of each treatment using the modified Rankin Scale (mRS). Thirteen patients were included (12 women, 1 man; median age 55 years at SN diagnosis) presenting with SN with a median follow-up of 3 years (range 2–17). In 11 patients, SN preceded or coincided with SS diagnosis. Most common neurological findings were ataxia and areflexia followed by paresthesia and pain. Lower limbs were more affected than upper limbs, neurological deficits were often symmetric and cranial nerves were affected in 3 patients. Seven patients were treated with corticosteroids, 7 with mycophenolate mofetil, 6 with hydroxychloroquine, 5 with intravenous immunoglobulins, 4 with cyclophosphamide, and 2 patients received other immunosuppressive drugs. At the beginning and at the end of follow-up, average mRS was 2.15 (median 2) and 2.38 (median 2), respectively. SS-related SN progression is heterogeneous but tends to be chronic, insidious, and debilitating despite treatment. From these data concerning a small number of patients, treatment strategies with corticosteroids in

  18. What is the impact of immunosuppressive treatment on the post-transplant renal osteopathy?

    PubMed

    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

  19. Cost-effectiveness of pharmacotherapy for autoimmune hepatitis.

    PubMed

    Heneghan, Michael A; Al-Chalabi, Thawab; McFarlane, Ian G

    2006-02-01

    In > 80% of patients with autoimmune hepatitis, steroid therapy alone or in combination with azathioprine results in disease remission. Treatment response results in reversal of fibrosis and excellent long-term survival in many patients, whereas untreated patients may expect a 10-year survival of < 30%. The use of azathioprine monotherapy (2 mg/kg/day) has gained widespread acceptance in maintaining remission in clinical practice. Although all patients with autoimmune hepatitis may not need treatment, particularly those with mild disease, alternative strategies are required in patients who have failed to achieve remission on standard therapy of steroids with or without azathioprine, or patients with azathioprine-induced drug toxicity. In such circumstances, the use of salvage therapy in the form of ciclosporin, tacrolimus or mycophenolate mofetil may be warranted. Liver transplantation is the treatment of choice for patients who present with subacute liver failure or decompensated cirrhosis. Salvage therapy results in an exponential rise in cost with each increment in therapeutic escalation. As an alternative to standard therapy, it has also been suggested that novel therapies such as ciclosporin, tacrolimus or mycophenolate mofetil be initiated to achieve remission. However, a > 10-fold cost differential exists between the charges associated with more potent immunosuppression and standard therapy. Therefore, in evaluating novel immunosuppression in autoimmune hepatitis, it behoves clinicians not only to consider end points pertaining to efficacy, but also end points pertaining to cost-effectiveness. Moreover, the exact role of pharmacogenomics and genotyping of thiopurine methyltransferase in patients with autoimmune hepatitis needs to be fully defined.

  20. Neuromyelitis optica (Devic's syndrome).

    PubMed

    Wingerchuk, Dean M; Weinshenker, Brian G

    2014-01-01

    Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system that selectively targets the optic nerve and spinal cord, although it may also target certain areas of the brain. The majority of cases are associated with relapses. A specific biomarker, an autoantibody that targets aquaporin-4, is present in the majority of patients and facilitates the diagnosis. Detection of this biomarker in serum has enabled recognition of an expanded spectrum of clinical disorders that previously would not have met diagnostic criteria for NMO. Aquaporin-4 IgG1 autoantibodies are pathogenic and produce lesions of the brain when injected intracerebrally or systemically. The clinical course of NMO is dominated by acute attacks. Progressive worsening of disability, as occurs in prototypic multiple sclerosis, is distinctly unusual. Corticosteroids and plasma exchange are useful for management of acute attacks. Several treatments used to prevent attacks of multiple sclerosis are ineffective in this condition; effective immunotherapies include azathioprine, mycophenolate mofetil and rituximab.

  1. Novel therapy for anti-glomerular basement membrane disease with IgA nephropathy: A case report

    PubMed Central

    XU, DECHAO; WU, JIANXIANG; WU, JUN; XU, CHENGGANG; ZHANG, YUQIANG; MEI, CHANGLIN; GAO, XIANG

    2016-01-01

    Anti-glomerular basement membrane (GBM) disease is characterized by circulating anti-GBM antibodies and deposition of these antibodies in the renal GBM. Renal involvement in anti-GBM is more severe when compared with other types of immune-mediated glomerulonephritis, and the majority of patients manifest progressive renal failure, leading to end-stage renal disease. In a limited number of cases, anti-GBM disease has been shown to be accompanied with other immune-mediated glomerulonephritis. The present study reported the case of a 50-year-old female patient presenting with rapidly progressive glomerulonephritis, who was diagnosed with anti-GBM disease with IgA nephropathy. The patient achieved a relatively good therapeutic outcome with administration of corticosteroids plus mycophenolate mofetil (MMF), which may prove to be a novel treatment option for this rare disease; however, the exact underlying mechanism requires further in-depth investigation. PMID:27168822

  2. Severe hepatotoxicity associated with the combination of spiramycin plus metronidazole.

    PubMed

    Hussein, Rola; El-Halabi, Mustapha; Ghaith, Ola; Jurdi, Nawaf; Azar, Cecilio; Mansour, Nabil; Sharara, Ala I

    2011-03-01

    Drug-induced liver injury (DILI) is a leading cause of acute liver failure and is the most frequent reason for post-marketing drug withdrawal. The spectrum of liver injury is wide, ranging from mild and subclinical injury, noticeable only on routine biochemical testing, to fulminant liver failure and death. Antibiotics, as a group, are a leading cause of DILI. We herein describe 4 patients who developed moderate to severe hepatotoxicity after exposure to a commercially - available combination of two antibiotics - spiramycin and metronidazole - commonly used for the treatment and prevention of periodontal infections. No other aetiology for liver injury could be identified in all cases. Two patients recovered spontaneously, and two had a more severe course, one responding to corticosteroids and mycophenolate mofetil and the other requiring liver transplantation for subacute massive necrosis.

  3. Calcineurin Inhibitors Associated Posterior Reversible Encephalopathy Syndrome in Solid Organ Transplantation

    PubMed Central

    Song, Turun; Rao, Zhengsheng; Tan, Qiling; Qiu, Yang; Liu, Jinpeng; Huang, Zhongli; Wang, Xianding; Lin, Tao

    2016-01-01

    Abstract Posterior reversible encephalopathy syndrome (PRES) is a rare neurologic side effect of calcineurin inhibitors (CNIs) with poorly understood clinical features. We report cases of 2 patients with PRES developing after kidney transplantation and summarize PRES clinical features through a literature review. The 1st case was a 28-year-old man who received a kidney transplant from a deceased donor. Initial immunosuppressive therapy consisted of tacrolimus/mycophenolate mofetil/prednisolone. He developed headache and blurred vision with visual field loss15 days after transplantation and generalized seizures 4 days later. The 2nd case was a 34-year-old man who received a living kidney transplant. His initial immunosuppressive therapy comprised tacrolimus/mycophenolate mofetil/prednisolone. Two months after transplantation, he developed seizures. Both patients were diagnosed with PRES based on neurological symptoms and magnetic resonance imaging (MRI) findings; they recovered after switching from tacrolimus to either a cyclosporine or a lower tacrolimus dose. CNI-associated PRES is an acute neurological syndrome with seizures, encephalopathy, visual abnormalities, headache, focal neurological deficits, and nausea/vomiting. It is always accompanied by hypertension. A fluid-attenuated inversion recovery signal MRI scan typically shows reversible subcortical white matter changes in the posterior cerebral hemisphere that usually occur within the 1st month after transplantation. CNI-associated PRES has a generally favorable prognosis with early diagnosis and prompt treatment including alternating or discontinuing CNIs and blood pressure control. CNI-associated PRES should be considered in patients exhibiting acute neurological symptoms after transplantation. Early diagnosis and immediate treatment are critical for a favorable prognosis. PMID:27057842

  4. Lupus nephritis in children – 10 years’ experience

    PubMed Central

    Kuźma-Mroczkowska, Elżbieta; Małdyk, Jadwiga; Pańczyk-Tomaszewska, Małgorzata

    2016-01-01

    Systemic lupus erythematosus (SLE) in children is usually more severe than it is in adults and there is a higher incidence of renal involvement. We described 18 children (16 girls, 2 boys) with lupus nephritis (LN), whose average age was 14.4 ±1.81 years. Disease activity was assessed according to SLEDAI (SLE Disease Activity Index). Renal biopsy was classified according to the INS/RPS (International Society of Nephrology/Renal Pathology Society). The patients were treated with steroids (100%) and pulses of cyclophosphamide (88.9%) or mycophenolate mofetil (11.1%), next azathioprine or mycophenolate mofetil with prednisone in reduced doses. In children with renal/multi-organ insufficiency and/or septicaemia, renal replacement therapy (27.8%), and plasmapheresis (22.2%) were used in the initial treatment. The SLEDAI initial activity was high in 44.4% and moderate in 55.6% of children. LN manifested as: nephrotic syndrome (83.3%), microhaematuria (100%), leukocyturia (60%), hypertension (72.2%), and acute renal injury (83.3%); mean GFR was 54.55 ±33.09 ml/min/1.73 m2. In the renal biopsy, class IV LN according to INS/RPS was mainly diagnosed (82%). At the end of follow-up, mean observation time 32.1±23.36 months: mean GFR was 90.87 ±12.13 ml/min/1.73 m2, proteinuria disappeared in 66.7% and decreased in 33.3% of children to the average of 1.7 g/day (range: 0.5-4.0 g/day), hypertension was observed in 83.4% of children. Intensive immunosuppressive treatment with pulses of cyclophosphamide in early stage of LN in children is very effective. PMID:27833441

  5. Borderline tuberculoid leprosy in childhood onset systemic lupus erythematosus patient.

    PubMed

    Lopes, V A P; Lourenço, D M R; Guariento, A; Trindade, M A; Avancini, J; Silva, C A

    2015-11-01

    Leprosy is a contagious and chronic systemic granulomatous disease caused by the bacillus Mycobacterium leprae. To our knowledge, no case of leprosy in a childhood-onset systemic lupus erythematosus (c-SLE) patient has been reported. For a period of 31 years, 312 c-SLE patients were followed at the Pediatric Rheumatology Unit of our University Hospital. One of them (0.3%) had tuberculoid leprosy skin lesions during the disease course and is here reported. A 10-year-old boy from Northwest of Brazil was diagnosed with c-SLE based on malar rash, photosensitivity, oral ulcers, lymphopenia, proteinuria, positive antinuclear antibodies, anti-double-stranded DNA, anti-Sm and anti-Ro/SSA autoantibodies. He was treated with prednisone, hydroxychloroquine and intravenous cyclophosphamide, followed by mycophenolate mofetil. At 12-years-old, he presented asymmetric skin lesions characterized by erythematous plaques with elevated external borders and hypochromic center with sensory loss. Peripheral nerve involvement was not evidenced. No history of familial cases of leprosy was reported, although the region where the patient resides is considered to be endemic for leprosy. Skin biopsy revealed a well-defined tuberculoid form. A marked thickening of nerves was observed, often destroyed by granulomas, without evidence of Mycobacterium leprae bacilli. At that time, the SLEDAI-2K score was 4 and he had been receiving prednisone 15 mg/day, hydroxychloroquine 200 mg/day and mycophenolate mofetil 3 g/day. Paucibacillary treatment for leprosy with dapsone and rifampicine was also introduced. In conclusion, we have reported a rare case of leprosy in the course of c-SLE. Leprosy should always be considered in children and adolescents with lupus who present skin abnormalities, particularly with hypoesthesic or anesthesic cutaneous lesions.

  6. Trends in the use of immunosuppressive agents by outpatients after renal transplantation at a medical center in southern Taiwan.

    PubMed

    Mao, P C-M; Lee, E K-L; Tseng, P-L

    2012-01-01

    Kidney transplantation has become an effective treatment for end-stage renal failure. This study analyzed trends in immunosuppressive agent use after renal transplantation at a medical center in southern Taiwan over a 9-year period (2000-2008) seeking to determine whether the trends were consistent with clinical trial outcomes and published guidelines. We identified adult outpatients who had diagnoses of renal transplantation and who had concurrent immunosuppressive drug claims. From 2000-2008, we discovered 39,189 prescriptions related to kidney transplantation. The overall medication consumption showed an increase from 4.9% to 31.9%. Cyclosporine was the main determinant of overall drug costs during these 9 years. The long-term prescribing trend for immunosuppressive use among renal transplantation outpatients showed a clear change during the course of the study. Tacrolimus and sodium mycophenolate/mycophenolate mofetil were used increasingly as combination therapy. However, our survey revealed that management of this transplantation population, especially regarding the use of either calcineurin inhibitor or corticosteroids, was based on potential long-term side effects.

  7. Sirolimus as maintenance treatment in an infant with life-threatening multiresistant pure red cell anemia/autoimmune hemolytic anemia.

    PubMed

    Miano, Maurizio; Poggi, Vincenzo; Banov, Laura; Fioredda, Francesca; Micalizzi, Concetta; Svahn, Johanna; Montobbio, Giovanni; Gallicola, Federica; Molinari, Angelo C; Parasole, Rosanna; Petruzziello, Fara; Fischer, Alain; Calvillo, Michaela; Dufour, Carlo

    2014-04-01

    A 9-month-old boy with life-threatening multiresistant pure red cell anemia/autoimmune hemolytic anemia within the frame of a possible, undiagnosed immune-mediated disease was initially treated with prednisone. Further-line therapies of the following 7 relapses included immunoglobulins, rituximab, cyclophosphamide, and alentuzumab followed by other maintenance treatments as cyclosporine, methotrexate, and mycophenolate. After all the administered therapies failed, the patient was successfully treated by splenectomy followed by fludarabine and then sirolimus as maintenance treatment. Relapses might have been caused by the lack of a complete debulking of triggering cells and/or ineffective maintenance therapy. Splenectomy and sirolimus may have played a complementary role in the management of both situations.

  8. Incontinence Treatment: Surgical Treatments

    MedlinePlus

    ... Bowel Incontinence Signs & Symptoms Symptoms of Incontinence Diarrhea Treatment Lifestyle Changes Dietary Tips Medication Bowel Management Biofeedback Surgical Treatments Newer Treatment Options Tips on Finding a Doctor ...

  9. State of the art - how I manage immune thrombocytopenia.

    PubMed

    Cooper, Nichola

    2017-03-10

    The management of patients with immune thrombocytopenia (ITP) is rapidly evolving. Over the last 15 years, a number of novel treatments have improved practice, with many steroid-sparing agents and a reduction in the progression to splenectomy. Although this has improved clinical care, many therapeutic challenges remain. There is no diagnostic test, no biomarkers to direct treatment and few comparative studies to help management decisions. Development of up to date guidelines is difficult with little high-grade evidence. First line treatment continues to be steroids and intravenous immunoglobulins (IVIG) although both are often poorly tolerated and not curative. Common second line treatments include rituximab, immunosuppressive agents, such as azathioprine and mycophenolate mofetil, and the thrombopoietin receptor agonists romiplostim and eltrombopag. There are no comparative studies to decide between these agents and treatment is generally individualized, depending on comorbidity. Use of splenectomy has declined and is generally reserved for patients with chronic disease, although the exact position of splenectomy is subject to debate. Further understanding of the cause of disease in individual patients may help guide treatment. Randomized controlled studies of common treatments and novel treatments for refractory patients are urgently needed.

  10. An Ensemble Approach for Expanding Queries

    DTIC Science & Technology

    2012-11-01

    mg left do all it pressure your No up history which MEDICAL take an there also HOURS x out a about above after again against...set a limit of ten recommendation terms per concept term expansion. An example below demonstrates the expansion tail for the concept term “ lupus ...nephritis” in query number 145. lupus nephritis (nephritis OR lupus lupus OR glomerulonephritis mycophenolate OR mofetil glomerulonephritis OR

  11. The safety and efficacy of MMF in lupus nephritis: a pilot study.

    PubMed

    Kingdon, E J; McLean, A G; Psimenou, E; Davenport, A; Powis, S H; Sweny, P; Burns, A

    2001-01-01

    Inducing and maintaining remission in patients with lupus nephritis may be difficult. Current treatments have significant toxicity. Mycophenolate mofetil (MMF) limits damage in murine models of lupus nephritis. We have assessed the efficacy and tolerability of MMF in the treatment of patients with long-standing or resistant lupus nephritis. We have treated 13 patients with biopsy proven lupus nephritis (two membranous nephropathy, four membranous nephropathy with superimposed proliferative changes, seven with proliferative glomerulonephritis). All patients had relapsed on conventional treatment or there were pressing indications to minimise steroid dosage or avoid alkylating agents. Nine out of 13 were treated with MMF and prednisolone, 3/10 with MMF alone and 1/10 with MMF, prednisolone and cyclosporine. Thirteen patients were treated with MMF for up to 37 months (median 25 months). Three patients were withdrawn from MMF during the first 8 months of treatment. The remainder tolerated MMF (median dose 1 g/day). Serological improvements were observed in 9/13 and steroid dosage was reduced in 8/10 patients. Infections occurred in 3/13. One patient relapsed. MMF significantly reduced the rate of decline of renal function. MMF should be considered in the treatment of long-standing or resistant lupus nephritis. Controlled clinical trials are required to confirm these findings.

  12. Immunosuppressive Treatment for Lupus Nephritis: Long-Term Results in 178 Patients

    PubMed Central

    Makarova, Tatiana A.; Zvonova, Elena V.; Anilina, Alina M.; Stolyarevich, Ekaterina S.

    2016-01-01

    Lupus nephritis is one of the most severe Systemic Lupus Erythematosus features, defining treatment modality and prognosis. Our retrospective study, including 178 patients treated for lupus nephritis during 23 years with mostly cyclophosphamide-based initial regimens followed by azathioprine or mycophenolic acid, demonstrates 84.8% of renal response with 19.2% of flares, 15-year patient survival 78.7% and kidney survival 76.3%, and low damage accrual. Both patient and kidney survival significantly differ for subgroups that achieved complete or partial renal response and nonresponders: patient 15-year survival 95% versus 65% versus 35%; kidney 15-year survival 100% versus 58% versus 0%, respectively. 51% (24 out of 47) of patients evaluated at the end of the study period sustained complete renal response; however, only 9 of them had 0 disease activity according to SELENA SLEDAI scale, while 13 patients had scores 2–4 due to the serological abnormalities only. We conclude that (1) initial treatment with cyclophosphamide followed by azathioprine is effective and can be used in agreement with International Guidelines until the evidence for biological treatments benefits becomes available; (2) complete and even partial renal response have positive prognostic value, and failure to achieve renal response negatively influences kidney and patient survival; (3) the validity of complete renal response in SLE is questioned by the absence of conventional definition of SLE remission. PMID:28050564

  13. Therapeutic variability in adult minimal change disease and focal segmental glomerulosclerosis

    PubMed Central

    Fernandez-Juarez, Gema; Villacorta, Javier; Ruiz-Roso, Gloria; Panizo, Nayara; Martinez-Marín, Isabel; Marco, Helena; Arrizabalaga, Pilar; Díaz, Montserrat; Perez-Gómez, Vanessa; Vaca, Marco; Rodríguez, Eva; Cobelo, Carmen; Fernandez, Loreto; Avila, Ana; Praga, Manuel; Quereda, Carlos; Ortiz, Alberto

    2016-01-01

    Background Variability in the management of glomerulonephritis may negatively impact efficacy and safety. However, there are little/no data on actual variability in the treatment of minimal change disease (MCD)/focal segmental glomerulosclerosis (FSGS) in adults. We assessed Spanish practice patterns for the management of adult nephrotic syndrome due to MCD or FSGS. The absence of reasonably good evidence on treatment for a disease often increases the variability substantially. Identification of evidence–practice gaps is the first necessary step in the knowledge-to-action cyclical process. We aim to analyse the real clinical practice in adults in hospitals in Spain and compare this with the recently released Kidney Disease: Improving Global Outcomes clinical practice guideline for glomerulonephritis. Methods Participating centres were required to include all adult patients (age >18 years) with a biopsy-proven diagnosis of MCD or FSGS from 2007 to 2011. Exclusion criteria included the diagnosis of secondary nephropathy. Results We studied 119 Caucasian patients with biopsy-proven MCD (n = 71) or FSGS (n = 48) from 13 Spanish hospitals. Of these patients, 102 received immunosuppressive treatment and 17 conservative treatment. The initial treatment was steroids, except in one patient in which mycophenolate mofetil was used. In all patients, the steroids were given as a single daily dose. The mean duration of steroid treatment at initial high doses was 8.7 ± 13.2 weeks and the mean global duration was 38 ± 32 weeks. The duration of initial high-dose steroids was <4 weeks in 41% of patients and >16 weeks in 10.5% of patients. We did find a weak and negative correlation between the duration of whole steroid treatment in the first episode and the number of the later relapses (r = −0.24, P = 0.023). There were 98 relapses and they were more frequent in MCD than in FSGs patients (2.10 ± 1.6 versus 1.56 ± 1.2; P = 0.09). The chosen treatment was mainly steroids (95

  14. A fast and fatal course of bronchiectasis: an unusual rare expression of chronic graft versus host disease. A case report

    PubMed Central

    Violeta, Labžentytė; Silvija, Zemnickienė; Edvardas, Danila; Virginija, Šileikienė; Rolandas, Zablockis; Vygantas, Gruslys

    2016-01-01

    Introduction. We report a case of a patient with acute myeloid leukaemia whose treatment with bone marrow transplantation (BMT) was followed by chronic graft versus host disease (GVHD) with lung involvement and bronchiectasis. This report illustrates an unusual course of a fast progression of the bronchiectasis due to BMT. Case description. A 33-year-old female was diagnosed with acute myeloid leukaemia. An allogeneic BMT was performed. One month after the transplantation, acute GVHD with skin involvement occurred. Treatment with prednisolone and mycophenolate mofetil (MMF) has been started. Nine months later, the patient was examined by a pulmonologist due to progressive dyspnoea. A pulmonary computed tomography (CT) scan showed normal parenchyma of the lungs and no changes to the bronchi. A CT scan performed 7 months later revealed bronchiectasis for the first time. No clinical response was associated with the treatment and the patient’s respiratory status progressively deteriorated. During the final hospitalization, a CT scan performed 1 year later revealed huge cystic bronchiectasis in both lungs. Despite the prophylaxis and treatment of GVHD and aggressive antimicrobial therapy, the patient died one year after the diagnosis of bronchiectasis. Conclusions. This case demonstrates that a fast and fatal course of bronchiectasis, that occurs after BMT, should always be considered as a possible manifestation of chronic graft versus host disease (cGVHD) following allogeneic BMT.

  15. Rapamycin improves lymphoproliferative disease in murine autoimmune lymphoproliferative syndrome (ALPS).

    PubMed

    Teachey, David T; Obzut, Dana A; Axsom, Kelly; Choi, John K; Goldsmith, Kelly C; Hall, Junior; Hulitt, Jessica; Manno, Catherine S; Maris, John M; Rhodin, Nicholas; Sullivan, Kathleen E; Brown, Valerie I; Grupp, Stephan A

    2006-09-15

    Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of abnormal lymphocyte survival caused by defective Fas-mediated apoptosis, leading to lymphadenopathy, hepatosplenomegaly, and an increased number of double-negative T cells (DNTs). Treatment options for patients with ALPS are limited. Rapamycin has been shown to induce apoptosis in normal and malignant lymphocytes. Since ALPS is caused by defective lymphocyte apoptosis, we hypothesized that rapamycin would be effective in treating ALPS. We tested this hypothesis using rapamycin in murine models of ALPS. We followed treatment response with serial assessment of DNTs by flow cytometry in blood and lymphoid tissue, by serial monitoring of lymph node and spleen size with ultrasonography, and by enzyme-linked immunosorbent assay (ELISA) for anti-double-stranded DNA (dsDNA) antibodies. Three-dimensional ultrasound measurements in the mice correlated to actual tissue measurements at death (r = .9648). We found a dramatic and statistically significant decrease in DNTs, lymphadenopathy, splenomegaly, and autoantibodies after only 4 weeks when comparing rapamycin-treated mice with controls. Rapamycin induced apoptosis through the intrinsic mitochondrial pathway. We compared rapamycin to mycophenolate mofetil, a second-line agent used to treat ALPS, and found rapamycin's control of lymphoproliferation was superior. We conclude that rapamycin is an effective treatment for murine ALPS and should be explored as treatment for affected humans.

  16. Relapsing macrophage activating syndrome in a 15-year-old girl with Still's disease: a case report

    PubMed Central

    2009-01-01

    Introduction Macrophage activating syndrome is a severe, potentially life-threatening condition that may accompany Still's disease. It is characterized by fever, hepatosplenomegaly, lymphadenopathy, severe cytopenia, serious liver dysfunction, coagulopathy and neurologic involvement. The principal treatment for patients with this syndrome includes etoposide 150 mg/2 M twice a week for two weeks, dexamethasone 10 mg/2 M for two weeks and cyclosporine 3 mg/kg to 5 mg/kg for a longer period. Cases of relapse of macrophage activating syndrome are relatively rare. Case presentation We describe the case of a 15-year-old Iraqi girl with Still's disease who developed macrophage activating syndrome with acute respiratory distress syndrome that required resuscitation and mechanical ventilation. Following intensive treatment, including high dose steroids and cyclosporine, the patient improved significantly. Two weeks after cyclosporine was discontinued, however, she was readmitted with an acute relapse of macrophage activating syndrome manifested by spiking fever, arthralgias, maculopapular rash and leukocytosis. This time the patient recovered following the reintroduction of treatment with cyclosporine and the addition of mycophenolate mofetil (Cellcept). Conclusion We believe that cyclosporine is a cornerstone for the treatment of Still's disease. We recommend continuing this medication for several weeks following the patient's clinical recovery in order to prevent macrophage activating syndrome relapses. PMID:20062775

  17. MMF and calcineurin taper in recurrent hepatitis C after liver transplantation: impact on histological course.

    PubMed

    Bahra, Marcus; Neumann, U I F P; Jacob, Dietmar; Puhl, Gero; Klupp, Jochen; Langrehr, Jan M; Berg, Thomas; Neuhaus, Peter

    2005-02-01

    Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT) is almost universal. The optimal immunosuppression for these patients is still under discussion. We designed a retrospective case-control study to evaluate the effect of mycophenolate mofetil (MMF) treatment in patients with recurrent hepatitis C. Forty patients with histologically proven hepatitis C recurrence after OLT were treated with MMF and calcineurin inhibitor (CNI) taper for 24 months and matched with 40 non-MMF-treated positive liver transplant recipients. Liver biopsies were obtained prior to MMF treatment and after a mean follow-up of 24 months. Histological changes were evaluated utilizing the Metavir score. Comparison of fibrosis/inflammation showed no impairment of histological findings during MMF treatment. In contrast, histological findings of the 40 non-MMF patients showed a significant increase of severity for inflammation/fibrosis. Viral load was similar in both groups. The course of alanin amino transferase (ALT) levels measured during MMF treatment showed a significant decrease. MMF in combination with CNI taper showed a positive effect on fibrosis progression, graft inflammation and ALT levels and may improve the clinical course of HCV after OLT, however, the antiviral properties of MMF are still unconfirmed.

  18. Haploidentical T Cell-Replete Transplantation with Post-Transplantation Cyclophosphamide for Patients in or above the Sixth Decade of Age Compared with Allogeneic Hematopoietic Stem Cell Transplantation from an Human Leukocyte Antigen-Matched Related or Unrelated Donor.

    PubMed

    Blaise, Didier; Fürst, Sabine; Crocchiolo, Roberto; El-Cheikh, Jean; Granata, Angela; Harbi, Samia; Bouabdallah, Reda; Devillier, Raynier; Bramanti, Stephania; Lemarie, Claude; Picard, Christophe; Chabannon, Christian; Weiller, Pierre-Jean; Faucher, Catherine; Mohty, Bilal; Vey, Norbert; Castagna, Luca

    2016-01-01

    It has recently been shown that a T cell-replete allogeneic (allo) hematopoietic stem cell transplantation (HSCT) from a haploidentical donor (haplo-ID) could be a valid treatment for hematological malignancies. However, little data exist concerning older populations. We provided transplantation to 31 patients over the age of 55 years from a haplo-ID and compared their outcomes with patients of the same ages who underwent transplantation from a matched related (MRD) or an unrelated donor (UD). All 3 groups were comparable, except for their conditioning. Patients in haplo-ID group received 2 days of post-transplantation high-dose cyclophosphamide followed by cyclosporine A and mycophenolate mofetil, whereas patients in other groups received pretransplantation antithymocyte globulin, cyclosporine A, and additional mycophenolate mofetil in case of 1-antigen mismatch. All patients but 1 in the haplo-ID group engrafted. The incidence of grades 2 to 4 acute graft-versus-host disease (GVHD) was not statistically different between recipients from haplo-ID (cumulative incidence, 23%) and MRD (cumulative incidence, 21%) transplantations but it was lower than after UD HSCT (cumulative incidence, 44%). No patient in the haplo-ID group developed severe chronic GVHD, compared with cumulative incidences of 16% and 14% after MRD (P = .02) and UD (P = .03) grafts, respectively. The cumulative incidences of relapse were similar in the 3 groups, whereas nonrelapse mortality after UD HSCT was 3-fold higher than after haplo-ID or MRD HSCT. Overall, 2-year overall survival (70%), progression-free survival (67%), and progression and severe chronic GVHD-free survival (67%) probabilities after haplo-ID did not statistically differ from MRD transplantation (78%, 64%, and 51%, respectively), although they were higher than after UD transplantation (51% [P = .08], 38% [P = .02], and 31% [P = .007]). We conclude that T cell-replete haplo-ID HSCT followed by post-transplantation high

  19. Chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Vanasse, Michel; Rossignol, Elsa; Hadad, Elie

    2013-01-01

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is characterized clinically by a progressive symmetrical weakness evolving over a period of at least 2 months. There is increased CSF protein and conduction block, reduced nerve conduction velocities, increased distal latencies, and/or absent F wave or prolonged F wave latency in two or more nerves. Incidence is lower in children (10 times less) than in adults, and the condition presents in an acute or subacute manner with frequent relapses. It is not associated with other systemic diseases such as neoplasia, diabetes mellitus, or monoclonal gammopathies. It appears to be immune-related as a variety of humoral and cellular autoimmune mechanisms have been implicated. Treatment is based on results obtained in randomized clinical trials (RCTs) conducted in adults as such studies are lacking in the pediatric population. The evolution of CIDP is more favorable in children than in adults, with 80-100% response rates to standard treatments (steroids, intravenous immunoglobulins, and/or plasmapheresis) and excellent outcome with complete functional recovery in most patients. Cases refractory to standard therapies do exist in children, for which azathioprine, methotrexate, and mycophenolate mofetil alone or more often in association with other treatments have been used. However, safety and efficacy data are still insufficient to give specific recommendations regarding the optimal choice.

  20. Anti-Inflammatory Therapy Modulates Nrf2-Keap1 in Kidney from Rats with Diabetes

    PubMed Central

    Arellano-Buendía, Abraham Said; Tostado-González, Montserrat; García-Arroyo, Fernando Enrique; Cristóbal-García, Magdalena; Loredo-Mendoza, María Lilia; Tapia, Edilia; Sánchez-Lozada, Laura-Gabriela; Osorio-Alonso, Horacio

    2016-01-01

    This study addressed the relationship of proinflammatory cytokines and Nrf2-Keap1 system in diabetic nephropathy. The experimental groups were control, diabetic, and diabetic treated with mycophenolate mofetil (MMF). The renal function, proinflammatory and profibrotic cytokines, oxidative stress, morphology, and nephrin expression were assessed. Diabetic group showed impaired renal function in association with oxidative stress and decreased Nrf2 nuclear translocation. These results were associated with increased mesangial matrix index, interstitial fibrosis, and increased nephrin expression in cortex and urine excretion. Additionally, interleukin-1β, IL-6, and transforming growth factor-β1 were increased in plasma and kidney. MMF treatment conserved renal function, prevented renal structural alterations, and partially prevented the proinflammatory and profibrotic cytokines overexpression. Despite that MMF treatment induced nephrin overexpression in renal tissue, preventing its urinary loss. MMF salutary effects were associated with a partial prevention of oxidative stress, increased Nrf2 nuclear translocation, and conservation of antioxidant enzymes in renal tissue. In conclusion, our results confirm that inflammation is a key factor in the progression of diabetic nephropathy and suggest that treatment with MMF protects the kidney by an antioxidant mechanism, possibly regulated at least in part by the Nrf2/Keap1 system, in addition to its well-known anti-inflammatory effects. PMID:26955430

  1. Anti-Inflammatory Therapy Modulates Nrf2-Keap1 in Kidney from Rats with Diabetes.

    PubMed

    Arellano-Buendía, Abraham Said; Tostado-González, Montserrat; García-Arroyo, Fernando Enrique; Cristóbal-García, Magdalena; Loredo-Mendoza, María Lilia; Tapia, Edilia; Sánchez-Lozada, Laura-Gabriela; Osorio-Alonso, Horacio

    2016-01-01

    This study addressed the relationship of proinflammatory cytokines and Nrf2-Keap1 system in diabetic nephropathy. The experimental groups were control, diabetic, and diabetic treated with mycophenolate mofetil (MMF). The renal function, proinflammatory and profibrotic cytokines, oxidative stress, morphology, and nephrin expression were assessed. Diabetic group showed impaired renal function in association with oxidative stress and decreased Nrf2 nuclear translocation. These results were associated with increased mesangial matrix index, interstitial fibrosis, and increased nephrin expression in cortex and urine excretion. Additionally, interleukin-1β, IL-6, and transforming growth factor-β1 were increased in plasma and kidney. MMF treatment conserved renal function, prevented renal structural alterations, and partially prevented the proinflammatory and profibrotic cytokines overexpression. Despite that MMF treatment induced nephrin overexpression in renal tissue, preventing its urinary loss. MMF salutary effects were associated with a partial prevention of oxidative stress, increased Nrf2 nuclear translocation, and conservation of antioxidant enzymes in renal tissue. In conclusion, our results confirm that inflammation is a key factor in the progression of diabetic nephropathy and suggest that treatment with MMF protects the kidney by an antioxidant mechanism, possibly regulated at least in part by the Nrf2/Keap1 system, in addition to its well-known anti-inflammatory effects.

  2. [Controversial issues in the Giornale Italiano di Nefrologia: how to treat patients with focal segmental glomerular sclerosis].

    PubMed

    Passerini, P; Scolari, F; Frasca', G M; Leoni, A; Venturelli, C; Dallera, N; Ravera, S; Balestra, E; Freddi, P; Fanciulli, E; D'Arezzo, M; Sagripanti, S

    2009-01-01

    Primary focal segmental glomerular sclerosis (FSGS) commonly presents with nephrotic syndrome. Spontaneous remission is rare and persistent nephrotic syndrome is a marker of poor prognosis. For this reason, obtaining remission using drugs with minimal side effects is desirable. The treatment of FSGS, however, represents a challenge. Not only is there a lack of prospective controlled trials, but FSGS is a syndrome of unknown pathophysiology, generally treated with drugs having a mechanism of action that is poorly understood in this setting, the use of which has often drawn criticism because it is based on empirical assumptions rather than pathogenetic evidence. At present, corticosteroids are the standard first-line approach in patients with idiopathic FSGS. Cytotoxic agents and cyclosporin A constitute a good therapeutic option for steroid-dependent patients or frequent relapsers. Mycophenolate mofetil, rituximab and plasmapheresis should be used as rescue treatment because further studies are required to determine their safety and efficacy. Clearly, real progress in FSGS treatment can only be obtained by research focused on the pathophysiology of this disease, so that a therapeutic approach can be defined that is based on reason rather than chance.

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

    PubMed

    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.

  4. Voltage-gated calcium channel autoimmune cerebellar degeneration

    PubMed Central

    McKasson, Marilyn; Clawson, Susan A.; Hill, Kenneth E.; Wood, Blair; Carlson, Noel; Bromberg, Mark; Greenlee, John E.

    2016-01-01

    Objectives: To describe response to treatment in a patient with autoantibodies against voltage-gated calcium channels (VGCCs) who presented with autoimmune cerebellar degeneration and subsequently developed Lambert-Eaton myasthenic syndrome (LEMS), and to study the effect of the patient's autoantibodies on Purkinje cells in rat cerebellar slice cultures. Methods: Case report and study of rat cerebellar slice cultures incubated with patient VGCC autoantibodies. Results: A 53-year-old man developed progressive incoordination with ataxic speech. Laboratory evaluation revealed VGCC autoantibodies without other antineuronal autoantibodies. Whole-body PET scans 6 and 12 months after presentation detected no malignancy. The patient improved significantly with IV immunoglobulin G (IgG), prednisone, and mycophenolate mofetil, but worsened after IV IgG was halted secondary to aseptic meningitis. He subsequently developed weakness with electrodiagnostic evidence of LEMS. The patient's IgG bound to Purkinje cells in rat cerebellar slice cultures, followed by neuronal death. Reactivity of the patient's autoantibodies with VGCCs was confirmed by blocking studies with defined VGCC antibodies. Conclusions: Autoimmune cerebellar degeneration associated with VGCC autoantibodies may precede onset of LEMS and may improve with immunosuppressive treatment. Binding of anti-VGCC antibodies to Purkinje cells in cerebellar slice cultures may be followed by cell death. Patients with anti-VGCC autoantibodies may be at risk of irreversible neurologic injury over time, and treatment should be initiated early. PMID:27088118

  5. [Autoimmune bullous skin disorders].

    PubMed

    Hertl, Michael; Niedermeier, Andrea; Borradori, Luca

    2010-09-01

    Autoimmune bullous skin disorders are rare, potentially fatal disorders of skin and mucous membranes which are associated with IgG or IgA autoantibodies against distinct adhesion molecules of the epidermis and dermal epidermal basement membrane zone, respectively. These autoantibodies lead to a loss of skin adhesion which shows up clinically as the formation of blisters or erosions. In pemphigus, loss of adhesion occurs within the epidermis while in the pemphigoids, linear IgA dermatosis, epidermolysis bullosa acquisita and dermatitis herpetiformis, loss of adhesion takes place within or underneath the basement membrane zone. The autoantigens of these disorders are largely identified and characterized. Making the diagnosis of autoimmune bullous skin diseases is based on histology and direct immunofluorescence of perilesional skin and the serological detection of autoantibodides by indirect immunofluorescence and recombinant autoantigens. Therapeutically, systemic treatment with glucocorticoids is combined with immunosuppressive adjuvants which allow for the fast reduction of systemic steroids. A prospective trial in pemphigus showed that adjuvant treatment with azathioprine, mycophenolate mofetil and cyclophosphamide, respectively, led to a significant reduction of the cummulative dose of systemic steroids until complete clinical remission was achieved. In bullous pemphigoid, topical treatment with clobetasol led to complete clinical remissions without major side effects seen when glucocorticoids were applied systemically. Therapeutic depletion of B cells by rituximab as a second line therapy has significantly improved the overall prognosis of pemphigus. Comparable controlled therapeutic trials have not yet been performed in dermatitis herpetiformis and epidermolysis bullosa acquisita.

  6. Clinical Features of Neuromuscular Disorders in Patients with N-Type Voltage-Gated Calcium Channel Antibodies

    PubMed Central

    Totzeck, Andreas; Mummel, Petra; Kastrup, Oliver; Hagenacker, Tim

    2016-01-01

    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. PMID:28078065

  7. Five years renal transplantation data: Single-center experience from Iraq.

    PubMed

    Ali, Ala A; Al-Saedi, Ali J; Al-Mudhaffer, Ali J; Al-Taee, Kais H

    2016-03-01

    Renal transplantation is the treatment of choice for patients with end-stage renal disease. In Iraq, renal transplantation started in 1973 and has continued until now with live donor transplantation, since deceased donor transplant program is not approved as yet. Long-term transplant data are still scarce. The aim of our study is to present data on transplantation and medical follow-up at one year and, survival analysis at one, three and five years. A total of 250 renal transplantations were performed at the Nephrology and Renal Transplantation Center, Baghdad between January 2009 and January 2014. It is a living donor, blood group compatible donor program. All patients received triple immunosuppression (calcineurine inhibitor, mycophenolate mofetil or mycophenolic acid, and steroid). The Kaplan-Meier method was used to determine the survival rate. There were 92 live related donors, 143 unrelated donors, and 15 spouse donors. The mean age was 34.07 ± 12.2 years. The one-year graft survival for related and unrelated donor transplants was 98.9% and 91.8%, respectively. Graft survival was lower (82.9%) in recipients with acute rejection episodes. The patient survival at one-year was 94%. The three-year graft and patient survival was 91% and 90%, respectively, and five-year survival for grafts and patients was 87.1% and 88%, respectively. The outcome of the renal transplantation in Iraq is improving. Long-term patient follow-up needs more meticulous attention. The development of renal transplant registry is critical for future planning. Moreover, renal transplantation practice in Iraq needs more social, religious, and governmental support.

  8. Everolimus Initiation With Early Calcineurin Inhibitor Withdrawal in De Novo Heart Transplant Recipients: Three-Year Results From the Randomized SCHEDULE Study.

    PubMed

    Andreassen, A K; Andersson, B; Gustafsson, F; Eiskjaer, H; Rådegran, G; Gude, E; Jansson, K; Solbu, D; Karason, K; Arora, S; Dellgren, G; Gullestad, L

    2016-04-01

    In a randomized, open-label trial, de novo heart transplant recipients were randomized to everolimus (3-6 ng/mL) with reduced-exposure calcineurin inhibitor (CNI; cyclosporine) to weeks 7-11 after transplant, followed by increased everolimus exposure (target 6-10 ng/mL) with cyclosporine withdrawal or standard-exposure cyclosporine. All patients received mycophenolate mofetil and corticosteroids. A total of 110 of 115 patients completed the 12-month study, and 102 attended a follow-up visit at month 36. Mean measured GFR (mGFR) at month 36 was 77.4 mL/min (standard deviation [SD] 20.2 mL/min) versus 59.2 mL/min (SD 17.4 mL/min) in the everolimus and CNI groups, respectively, a difference of 18.3 mL/min (95% CI 11.1-25.6 mL/min; p < 0.001) in the intention to treat population. Multivariate analysis showed treatment to be an independent determinant of mGFR at month 36. Coronary intravascular ultrasound at 36 months revealed significantly reduced progression of allograft vasculopathy in the everolimus group compared with the CNI group. Biopsy-proven acute rejection grade ≥2R occurred in 10.2% and 5.9% of everolimus- and CNI-treated patients, respectively, during months 12-36. Serious adverse events occurred in 37.3% and 19.6% of everolimus- and CNI-treated patients, respectively (p = 0.078). These results suggest that early CNI withdrawal after heart transplantation supported by everolimus, mycophenolic acid and steroids with lymphocyte-depleting induction is safe at intermediate follow-up. This regimen, used selectively, may offer adequate immunosuppressive potency with a sustained renal advantage.

  9. UGT1A9 -275T>A/-2152C>T polymorphisms correlate with low MPA exposure and acute rejection in MMF/tacrolimus-treated kidney transplant patients.

    PubMed

    van Schaik, R H N; van Agteren, M; de Fijter, J W; Hartmann, A; Schmidt, J; Budde, K; Kuypers, D; Le Meur, Y; van der Werf, M; Mamelok, R; van Gelder, T

    2009-09-01

    Mycophenolate mofetil (MMF) is an immunosuppressive drug commonly used in the context of kidney transplantation. Exposure to the active metabolite mycophenolic acid (MPA) is associated with risk of allograft rejection. MPA pharmacokinetics varies between individuals, the potential cause being the presence of genetic polymorphisms in key enzymes. We genotyped 338 kidney transplant patients for UGT1A8, UGT1A9, UGT2B7, and MRP2 polymorphisms and recorded MPA exposure and biopsy-proven acute rejections (BPARs) during a 1-year follow-up. Tacrolimus-treated patients who were UGT1A9 -275T>A and/or -2152C>T carriers displayed a 20% lower MPA area under the concentration-time curve from 0 to 12 h (AUC(0-12)) (P = 0.012). UGT1A9*3 carriers displayed a 49% higher MPA AUC(0-12) when treated with tacrolimus and a 54% higher MPA AUC(0-12) when treated with cyclosporine (P < 0.005). Cyclosporine-treated UGT1A8*2/*2 (518GG) patients had an 18% higher MPA AUC(0-12) compared with noncarriers. Carrying the UGT1A9 -275T>A and/or -2152C>T polymorphism significantly predicted acute rejection in fixed-dose (FD) MMF-treated patients receiving tacrolimus (odds ratio 13.3, 95% confidence interval 1.1-162.3; P < 0.05). UGT1A9 -275T>A and/or -2152C>T genotyping may identify patients at risk of MPA underexposure and acute rejection when receiving treatment with MMF and tacrolimus.

  10. Increased Telomere Attrition After Renal Transplantation—Impact of Antimetabolite Therapy

    PubMed Central

    Luttropp, Karin; Nordfors, Louise; McGuinness, Dagmara; Wennberg, Lars; Curley, Hannah; Quasim, Tara; Genberg, Helena; Sandberg, John; Sönnerborg, Isabella; Schalling, Martin; Qureshi, Abdul Rashid; Bárány, Peter; Shiels, Paul G.; Stenvinkel, Peter

    2016-01-01

    Background The uremic milieu exposes chronic kidney disease (CKD) patients to premature ageing processes. The impact of renal replacement therapy (dialysis and renal transplantation [RTx]) or immunosuppressive treatment regimens on ageing biomarkers has scarcely been studied. Methods In this study telomere length in whole blood cells was measured in 49 dialysis patients and 47 RTx patients close to therapy initiation and again after 12 months. Forty-three non-CKD patients were included as controls. Results Non-CKD patients had significantly (P ≤ 0.01) longer telomeres than CKD patients. Telomere attrition after 12 months was significantly greater in RTx patients compared to dialysis patients (P = 0.008). RTx patients receiving mycophenolate mofetil (MMF) had a greater (P = 0.007) degree of telomere attrition compared to those treated with azathioprine. After 12 months, folate was significantly higher in RTx patients than in dialysis patients (P < 0.0001), whereas the opposite was true for homocysteine (P < 0.0001). The azathioprine group had lower levels of folate after 12 months than the MMF group (P = 0.003). Conclusions The associations between immunosuppressive therapy, telomere attrition, and changes in folate indicate a link between methyl donor potential, immunosuppressive drugs, and biological ageing. The hypothesis that the increased telomere attrition, observed in the MMF group after RTx, is driven by the immunosuppressive treatment, deserves further attention. PMID:27990481

  11. Infection risk in systemic lupus erythematosus patients: susceptibility factors and preventive strategies.

    PubMed

    Danza, A; Ruiz-Irastorza, G

    2013-10-01

    Infection is one of the leading causes of morbidity and mortality in systemic lupus erythematosus (SLE). Bacterial infections are most frequent, followed by viral and fungal infections. The impaired cellular and humoral immune functions seen in patients with SLE are predisposing conditions, whilst disease activity, prednisone doses over 7.5-10 mg/day, high doses of methylprednisolone or cyclophosphamide are well-recognised risk factors for infection. The first six months after rituximab treatment and the use of more than three courses are also associated with an increased susceptibility for infection. It has not been established whether belimumab, azathioprine and mycophenolate mofetil increase the risk of serious infections. Most vaccines are effective and safe in SLE patients, although vaccination should be avoided during periods of active disease. Live virus vaccines are contraindicated for immunosuppressed patients. Influenza and pneumococcal vaccines are universally recommended. Tuberculosis prophylaxis should be considered in selected cases. Therefore, it is advisable not to exceed doses of 5 mg/day of prednisone in chronic treatment. Methylprednisolone and cyclophosphamide should be used in low-dose regimens. Antimalarials have a well-known protective role against infection, in addition to other beneficial properties, thus, hydroxychloroquine is recommended for all SLE patients where no contraindication exists.

  12. Managing immune checkpoint-blocking antibody side effects.

    PubMed

    Postow, Michael A

    2015-01-01

    Immune checkpoint-blocking antibodies that enhance the immune system's ability to fight cancer are becoming important components of treatment for patients with a variety of malignancies. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) was the first immune checkpoint to be clinically targeted, and ipilimumab, an inhibitor of CTLA-4, was approved by the U.S. Food and Drug Administration (FDA) for patients with advanced melanoma. The programmed cell death-1 (PD-1) receptor and one of its ligands, PD-L1, more recently have shown great promise as therapeutic targets in a variety of malignancies. Nivolumab and pembrolizumab recently have been FDA- approved for patients with melanoma and additional approvals within this therapeutic class are expected. The use of anti-CTLA-4 and anti-PD-1/PD-L1 antibodies is associated with side effects known as immune-related adverse events (irAEs). Immune-related adverse events affect the dermatologic, gastrointestinal, hepatic, endocrine, and other organ systems. Temporary immunosuppression with corticosteroids, tumor necrosis factor-alpha antagonists, mycophenolate mofetil, or other agents can be effective treatment. This article describes the side-effect profile of the checkpoint-blocking antibodies that target CTLA-4 and PD-1/PD-L1 and provides suggestions on how to manage specific irAEs.

  13. [Membranous kidney diseases in adults].

    PubMed

    Sobarzo Toro, Martín; Vilches, Antonio

    2004-01-01

    Membranous nephropathy is the most common histologic phenotype associated with the primary nephrotic syndrome in adults and the second most common etiological diagnosis in over sixteen hundred renal biopsies on native kidneys processed at our institution over a 30 year period. Renal survival at 10 years is about 70%, but the course of the disease is related to a series of factors which have constituted the basis for mathematical models developed to predict the natural history in a given individual. These factors are gender, age, renal function at the time of diagnosis, presence of the nephrotic syndrome, high blood pressure and the degree of structural damage. Although in low risk patients a period of observation and the use of ACE inhibitors is a reasonable option, most nephrologists would elect to use pharmacological treatment to induce remissions of proteinuria and preserve renal function. The use of steroids and cytotoxic agents in alternating monthly cycles over six months is firmly supported by controlled, randomized clinical trials. If patients are resistant to this regimen or clinical considerations indicate it may be inappropriately toxic, the use of cyclosporin over 6 to 12 months is also a good choice, and it has been shown to be useful even in the context of deteriorating renal function. Mycophenolate mofetil and possibly rituximab may be options of last resort before considering the patient resistant to therapy. At all times, treatment of hypertension, non-specific antiproteinuric measures, and preventing complications of the nephrotic state should be top priorities in the overall therapeutic strategy.

  14. Diagnosis and Management of Autoimmune Hepatitis: Current Status and Future Directions

    PubMed Central

    Czaja, Albert J.

    2016-01-01

    Autoimmune hepatitis is characterized by autoantibodies, hypergammaglobulinemia, and interface hepatitis on histological examination. The features lack diagnostic specificity, and other diseases that may resemble autoimmune hepatitis must be excluded. The clinical presentation may be acute, acute severe (fulminant), or asymptomatic; conventional autoantibodies may be absent; centrilobular necrosis and bile duct changes may be present; and the disease may occur after liver transplantation or with features that suggest overlapping disorders. The diagnostic criteria have been codified, and diagnostic scoring systems can support clinical judgment. Nonstandard autoantibodies, including antibodies to actin, α-actinin, soluble liver antigen, perinuclear antineutrophil antigen, asialoglycoprotein receptor, and liver cytosol type 1, are tools that can support the diagnosis, especially in patients with atypical features. Prednisone or prednisolone in combination with azathioprine is the preferred treatment, and strategies using these medications in various doses can ameliorate treatment failure, incomplete response, drug intolerance, and relapse after drug withdrawal. Budesonide, mycophenolate mofetil, and calcineurin inhibitors can be considered in selected patients as frontline or salvage therapies. Molecular (recombinant proteins and monoclonal antibodies), cellular (adoptive transfer and antigenic manipulation), and pharmacological (antioxidants, antifibrotics, and antiapoptotic agents) interventions constitute future directions in management. The evolving knowledge of the pathogenic pathways and the advances in technology promise new management algorithms. PMID:26934884

  15. World experience after more than a decade of clinical hand transplantation: update on the French program.

    PubMed

    Petruzzo, Palmina; Dubernard, Jean Michel

    2011-11-01

    The first hand transplantation was realized in Lyon and the results achieved in this case showed the feasibility of the surgical technique, the efficacy of the immunosuppressive protocol, the limited adverse effects and the importance of a patient's compliance and rehabilitation to ensure graft viability and functional recovery. Based on these findings and the positive results achieved in other single hand transplants realized around the world the authors performed also the first double hand transplantation, then followed by other four cases. The recipients received the same immunosuppressive treatment including tacrolimus, prednisone, mycophenolate mofetil and antithymocyte globulins for induction, nevertheless they showed some episodes of acute rejection episodes which reversed after a prompt treatment. All the bilateral hand grafted patients showed a relevant sensorimotor recovery particularly of sensibility and activity of intrinsic muscles. They were able to perform the majority of daily activities and to lead a normal social life. On the basis of the authors' experience the results achieved in hand allotransplantation are very encouraging as major adverse effects due to surgery and immunosuppressive regimen did not occur and patients' quality of life improved considerably.

  16. Pemphigus vulgaris with nail involvement presenting with vegetating and verrucous lesions.

    PubMed

    Mascarenhas, R; Fernandes, B; Reis, J P; Tellechea, O; Figueiredo, A

    2003-12-01

    We report the case of a 68-year-old female with longstanding insulin-treated diabetes mellitus, observed for the first time in our department in August 1999 with multiple painful erosive lesions of the oral cavity and many bullous or erosive lesions on the abdominal wall, back, and thigh. She also had vegetating and verrucous lesions, similar to common warts, involving the hands and feet, mainly on the palms, palmar surface of the fingers, and nail folds. Her lesions were present for 1 year. Skin and mucous biopsies showed the characteristic histopathologic findings of pemphigus vulgaris, with an epidermal intercellular IgG deposition on direct immunofluorescence. Histology of a warty lesion of the finger also showed suprabasal acantholysis. After partial improvement with low doses of oral steroids and azathioprine, her disease progressed to involve the oral cavity, trunk, hands, feet, and scalp. Control of her disease required successive treatments of mycophenolate mofetil and cyclophosphamide, as well as corticosteroids. A partial response was obtained with all these treatments. After being controlled by cyclophosphamide that was slowly tapered, she is now well controlled with azathioprine and oral steroids, showing only discrete lesions of the oral mucosa after 1 year of followup. We report this case of pemphigus vulgaris with unusual clinical aspects, namely vegetating and verrucous lesions as well as nail involvement, rarely described in this disease.

  17. [Lupus anticoagulant-hypoprothrombinemia syndrome revealing systemic lupus in an 11-year old girl in a context of clinical and biological emergency].

    PubMed

    Favier, Rémi; Kheyar, Tassadit; Renolleau, Sylvain; Tabone, Marie Dominique; Favier, Marie; Ulinski, Tim

    2012-01-01

    We report a case of lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) in an 11 year old girl initially hospitalized for bleeding. The patient presented with petechia, persisting bleeding after tooth extraction performed two days before, nephritic syndrome (renal failure, proteinuria and macroscopic hematuria), severe anemia, thrombocytopenia, lymphopenia. The association of these abnormalities suggested LAHPS secondary to severe systemic lupus. Immediate treatment with fresh frozen plasma and intravenous immunoglobulins (400 mg/kg/5d) was started and followed by steroid (500 mg/d) and cyclophosphamide (800 mg/m(2)) pulse therapy leading to rapid improvement of bleeding, renal involvement and prothrombin levels within 13 days. Lupus diagnosis was confirmed by immunological investigations and renal biopsy. Two early relapses occurred despite adequate treatment. After a follow-up of two years, no further disease activity is noted while the patient is treated only by mycophenolate mofetil (1 200 mg/m(2)/d). LAHPS did not relapse during this follow-up.

  18. [Molecular mechanisms of action of some immunosuppressive drugs].

    PubMed

    Liberman, Ana C; Druker, Jimena; Refojo, Damián; Arzt, Eduardo

    2008-01-01

    A number of natural and synthetic substances are used in the treatment of immunological disorders. The immunosuppressive drugs are widely utilized in clinical treatments of autoimmune disorders, in the prevention of transplant rejection as well as in non-autoimmune diseases such as allergy. The design of immunosuppressive therapies is based on the control of the exacerbated immune response. The pathophysiologic mean of this concept is to modulate the 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.

  19. Guideline of Chronic Urticaria Beyond

    PubMed Central

    Fine, Lauren M.

    2016-01-01

    Urticaria is a relatively common condition that if chronic can persist for weeks, months or years and affect quality of life significantly. The etiology is often difficult to determine, especially as it becomes chronic. Many cases of chronic urticaria are thought to be autoimmune, although there is no consensus that testing for autoimmunity alters the diagnostic or management strategies or outcomes. Many times, urticaria is easily managed with antihistamines and/or short courses of oral corticosteroids, but too often control is insufficient and additional therapies must be added. For years, immune modulating medications, such as cyclosporine and Mycophenolate Mofetil, have been used in cases refractory to antihistamines and oral corticosteroids, although the evidence supporting their efficacy and safety has been limited. Omalizumab was recently approved for the treatment of chronic urticaria unresponsive to H1-antagonists. This IgG anti-IgE monoclonal antibody has been well demonstrated to safely and effectively control chronic urticaria at least partially in approximately 2/3 of cases. However, the mechanism of action and duration of treatment for omalizumab is still unclear. It is hoped that as the pathobiology of chronic urticaria becomes better defined, future therapies that target specific mechanistic pathways will be developed that continue to improve the management of these often challenging patients. PMID:27334777

  20. Myasthenia gravis: an update for the clinician.

    PubMed

    Sieb, J P

    2014-03-01

    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.

  1. Myasthenia gravis: an update for the clinician

    PubMed Central

    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

  2. Autoimmune Hemolytic Anemia in Children: Mayo Clinic Experience.

    PubMed

    Sankaran, Janani; Rodriguez, Vilmarie; Jacob, Eapen K; Kreuter, Justin D; Go, Ronald S

    2016-04-01

    We studied 35 pediatric patients with autoimmune hemolytic anemia seen at Mayo Clinic from 1994 to 2014. The median age was 10.0 years and 65.7% were males. Most had warm antibodies (80.0%) and some secondary to viral (14.3%) or autoimmune disorders (31.4%). Seven (20.0%) patients presented with Evans syndrome, 3 of whom also had common variable immunodeficiency. The median hemoglobin at diagnosis was 6.1 g/dL and 62.8% patients required red cell transfusions. The severity of anemia was worse among children below 10 years (median 5.5 vs. 7.0 g/dL, P=0.01). Steroid was the initial treatment for 88.5% patients, with overall response rate of 82.7% (68.5% complete, 14.2% partial) and median response duration of 10.7 months (range, 0.2 to 129.7+ mo). After median follow-up of 26.6 months, 8 (22.8%) patients relapsed. Salvage treatments included splenectomy, intravenous immunoglobulin, rituximab, and mycophenolate mofetil. Infectious complications occurred in 9 (25.7%) patients and 1 patient died of cytomegalovirus infection. Four patients had cold agglutinin disease and 3 (75.0%) responded to steroids. Autoimmune hemolytic anemia is a rare disorder in pediatric population and most respond well to steroids regardless of the type of antibody. Infectious complications are common and screening for immunodeficiency is recommended among those with Evans syndrome.

  3. [Case of MMF monotherapy for membranous nephropathy].

    PubMed

    Kobayashi, Mioko; Kojima, Chiari; Sugiura, Hidekazu; Aoki, Asuka; Itabashi, Mitsuyo; Tsukada, Misao; Takei, Takashi; Uchida, Keiko; Nitta, Kosaku

    2010-01-01

    We report the case of a 58-year-old male patient who visited our hospital for the management of edema and proteinuria. He was diagnosed as having nephrotic syndrome, with serum total protein and albumin levels of 4.6 g/dL and 2.1 g/dL, respectively, and a urinary protein excretion level of 6.0 g/day. A percutaneous renal biopsy showed features of membranous glomerulonephritis, with capillary-wall granular deposits of IgG and C3 on immunofluorescence and subepithelial immune complex deposits on electron microscopy. No other secondary cause of membranous glomerulopathy was found even after extensive investigations. The patient was started on mycophenolate mofetil (MMF) monotherapy (1,500 mg/day), and 18 months after the start of this therapy, the proteinuria decreased to 0.5 g/day, with return to a normal serum albumin level. No digestive symptoms, kidney function worsening or increase in blood pressure were noted during treatment. These findings suggest that MMF monotherapy is effective and safe for the treatment of membranous nephropathy.

  4. Combined MMF and insulin therapy prevents renal injury in experimental diabetic rats.

    PubMed

    Wu, Xiaoyan; Zha, Dongqing; Xiang, Guangsheng; Zhang, Bo; Xiao, Shu-Yuan; Jia, Ruhan

    2006-12-01

    Conventional therapies for diabetic mellitus are not effective in preventing the progression from early diabetic nephropathy (DN) to end-stage renal disease. The role of inflammation in the pathogenesis of DN has been implicated both clinically and experimentally, which provides an alternative therapeutic target for DN. Anti-inflammatory impact of mycophenolate mofetil (MMF) alone and in combination with insulin had been observed in a rat model of experimental DN. In this study, the diabetic rats were subjected to different treatments. Compared to control, the expression levels of CD68, NGF, and NF-kappaB p65, as determined immunohistochemically, were elevated in diabetic rats. Treatment with combined MMF/insulin is associated with a significant reduction in renal tissue of NGF and NF-kappaB p65 expression, macrophage infiltration. It also partially improved the renal function and attenuated renal hypertrophy at early stage of DN. CD68 was found to positively correlate with urinary albumin excretion and NGF. The combined use of MMF/insulin seemed to offer more protections in rats with experimental diabetic renal injury, and the protective effects of MMF might be due to its anti-inflammatory actions through inhibition of NF-kappaB activation and reduction of T cells and macrophage infiltration and/or other kidney chemokine productions.

  5. Long-term, maintenance MMF monotherapy improves the fibrosis progression in liver transplant recipients with recurrent hepatitis C.

    PubMed

    Manzia, Tommaso Maria; Angelico, Roberta; Toti, Luca; Bellini, Maria Irene; Sforza, Daniele; Palmieri, Giampiero; Orlando, Giuseppe; Tariciotti, Laura; Angelico, Mario; Tisone, Giuseppe

    2011-05-01

    Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (LT) is universal. We designed a retrospective case-control study to evaluate the effect of mycophenolate mofetil (MMF) monotherapy in patients with recurrent hepatitis C. Fifteen patients with histologically proven hepatitis C recurrence after LT were switched from calcineurin inhibitors (CNIs) to MMF monotherapy because of impairment of kidney function and/or metabolic side effects, and treated for 48 months (MMF group). Fifteen well-matched LT recipients who continued to receive CNIs therapy over the same period served as control group. Demographics, clinical data, time after LT, and baseline liver biopsies were similar in the two groups. There was no worsening of hepatic fibrosis during the study in the MMF group [2.6 ± 1.5 (baseline) Ishak Units vs. 2.7 ± 1.8 (after 48 months of MMF treatment), P = 0.6]. In contrast, a significant increase in the fibrosis score [2 ± 1.1 (baseline) vs. 3.2 ± 1.7 (after 48 months of CNI treatment), P = 0.0002] was observed in the control group. The yearly fibrosis progression rate was of 0.05 ± 0.44 in the MMF group and 0.33 ± 0.24 in the CNI group (P = 0.04). MMF monotherapy is associated with a favourable effect on hepatic fibrosis progression in HCV liver transplant recipients.

  6. [Hemolytic anemia caused by graft-versus-host reaction in ABO-nonidentical renal transplants from blood group O donors].

    PubMed

    Peces, R; Díaz Corte, C; Navascués, R A

    2001-01-01

    Acute hemolytic anemia is one of the side effects associated with cyclosporin and tacrolimus therapy, and three mechanisms have been described to account for hemolytic anemia in patients receiving these drugs: drug induced hemolysis, autoimmune hemolysis and alloimmune hemolysis resulting from donor lymphocytes derived from the allograft (passenger lymphocyte syndrome). We report four cases of renal transplant recipients who developed alloimmune hemolytic anemia due to minor ABO incompatibility while under treatment with cyclosporin (two) and tacrolimus (two). The anti-erythrocyte antibodies responsible for hemolysis were of the IgG isotype and showed anti-A or anti-B specificity. These findings suggest that the hemolysis could be related to alloantibodies derived from the clonal development of donor B lymphocytes in the recipients (microchimerism). In summary, hemolytic anemia due to ABO-minor incompatibility occurs infrequently after renal transplantation. Risks are higher for patients A, B or AB blood group receiving an O blood group graft under treatment with cyclosporin or tacrolimus. Follow-up of these patients is warranted for the early detection and optimal management may be achieved by reduction of immunosuppression and change to mycophenolate mofetil.

  7. Regulated expression of the MRP8 and MRP14 genes in human promyelocytic leukemic HL-60 cell treated with the differentiation-inducing agents mycophenolic acid and 1{alpha},25-Dihydroxyvitamin D{sub 3}

    SciTech Connect

    Warner-Bartnicki, A.L.; Murao, S.; Collart, F.R.; Huberman, E.

    1992-12-31

    The calcium-binding proteins MRP8 and MEP14 are present in mature monomyelocytic cells and are induced during differentiation. Previous studies have demonstrated that the proteins may mediate the growth arrest in differentiating HL-60 cells. We determined the levels of a protein complex (PC) containing MRP8 and MRP14 and investigated the mechanism by which the genes encoding these proteins are regulated in HL-60 cells treated with the differentiation-inducing agent mycophenorc acid (MPA)While the PC was barely detectable in untreated cells, MPA treatment resulted in elevated levels of the PC which were maximal at 3-4 d, and were found to directly parallel gains in the steady-state levels of MRP8 and MRP14 MRNA. Transcription studies with the use of nuclear run-on experiments revealed increased transcription initiation at the MRP8 and MRP14 promoters after MPA treatment. 1{alpha},25-Dihydroxyvitamin D{sub 3}, which induces HL-60 cell differentiation by another mechanism, was also found to increase transcription initiation at the MRP8 and MRP14 promoters. Our results suggest that this initiation is the major control of maturation agent-mediated increases in MRP8 and MRPl4 gene expression, and support a role for the PC in terminal differentiation of human monomyelocytic cells.

  8. Hyperbaric treatment

    NASA Technical Reports Server (NTRS)

    Amoroso, Michael T.

    1990-01-01

    Viewgraphs on hyperbaric treatment are presented. Topics covered include: hyperbaric treatment - purpose; decompression sickness; sources of decompression sickness; physical description; forms of decompression sickness; hyperbaric treatment of decompression sickness; and duration of treatment.

  9. A review of treatment modalities for Middle East Respiratory Syndrome.

    PubMed

    Mo, Yin; Fisher, Dale

    2016-12-01

    The Middle East Respiratory Syndrome coronavirus (MERS-CoV) has been a focus of international attention since its identification in 2012. Epidemiologically it is characterized by sporadic community cases, which are amplified by hospital-based outbreaks. Healthcare facilities in 27 countries from most continents have experienced imported cases, with the most significant outbreak involving 186 cases in Korea. The mortality internationally is 36% and guidance for clinical management has yet to be developed. Most facilities and healthcare providers outside of the Middle East receiving patients have no or little experience in the clinical management of MERS. When a case does occur there is likely little time for a critical appraisal of the literature and putative pharmacological options. We identified published literature on the management of both MERS-CoV and the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) through searches of PubMed and WHO and the US CDC websites up to 30 April 2016. A total of 101 publications were retrieved for critical appraisal. Most published literature on therapeutics for MERS are in vitro experiments, animal studies and case reports. Current treatment options for MERS can be categorized as: immunotherapy with virus-specific antibodies in convalescent plasma; polyclonal and monoclonal antibodies produced in vitro or in genetically modified animals; and antiviral agents. The use of any therapeutics in MERS-CoV remains investigational. The therapeutic agents with potential benefits and warranting further investigation include convalescent plasma, interferon-β/ribavirin combination therapy and lopinavir. Corticosteroids, ribavirin monotherapy and mycophenolic acid likely have toxicities that exceed potential benefits.

  10. Therapy of NMO spectrum disorders

    PubMed Central

    Biswas, Atanu; Mukherjee, Arabinda

    2015-01-01

    Neuromyelitis optica (NMO) is an autoimmune demyelinating condition of the central nervous system often associated with aquaporin-4 (AQP4) autoantibodies manifesting as severe optic neuritis and long segment myelitis with tendency to relapse. Seronegative patients and who do not meet the NMO criteria are classified as having NMO Spectrum Disorder (NMOSD), but are treated identically to clinically definite NMO. Acute relapse is treated with intravenous methylprednisolone for 5 days with or without subsequent treatment with plasma exchange (PE). This must be followed by oral steroid to prevent rebound worsening and further relapse. For relapse prevention, immunosuppressive agents that have been found to be effective are azathioprine, rituximab, mycophenolate mofetil, methotrexate, and mitoxantrone; although none of which have been validated in randomized, controlled trial. Some patients do relapse with monotherapy, and switching to more effective agent or use of combination therapy is beneficial in such situation. There is no consensus about the duration of preventive therapy, but generally 2-3 years of relapse-free period is considered the minimum, taking into account the risks of long-term toxicity of these agents. PMID:26538843

  11. Pancreas transplantation: review

    PubMed Central

    Meirelles, Roberto Ferreira; Salvalaggio, Paolo; Pacheco-Silva, Alvaro

    2015-01-01

    ABSTRACT Vascularized pancreas transplantation is the only treatment that establishes normal glucose levels and normalizes glycosylated hemoglobin levels in type 1 diabetic patients. The first vascularized pancreas transplant was performed by William Kelly and Richard Lillehei, to treat a type 1 diabetes patient, in December 1966. In Brazil, Edison Teixeira performed the first isolated segmental pancreas transplant in 1968. Until the 1980s, pancreas transplants were restricted to a few centers of the United States and Europe. The introduction of tacrolimus and mycophenolate mofetil in 1994, led to a significant outcome improvement and consequently, an increase in pancreas transplants in several countries. According to the International Pancreas Transplant Registry, until December 31st, 2010, more than 35 thousand pancreas transplants had been performed. The one-year survival of patients and pancreatic grafts exceeds 95 and 83%, respectively. The better survival of pancreatic (86%) and renal (93%) grafts in the first year after transplantation is in the simultaneous pancreas-kidney transplant group of patients. Immunological loss in the first year after transplant for simultaneous pancreas-kidney, pancreas after kidney, and pancreas alone are 1.8, 3.7, and 6%, respectively. Pancreas transplant has 10 to 20% surgical complications requiring laparotomy. Besides enhancing quality of life, pancreatic transplant increases survival of uremic diabetic patient as compared to uremic diabetic patients on dialysis or with kidney transplantation alone. PMID:26154551

  12. Chimeric 2C10R4 anti-CD40 antibody therapy is critical for long-term survival of GTKO.hCD46.hTBM pig-to-primate cardiac xenograft.

    PubMed

    Mohiuddin, Muhammad M; Singh, Avneesh K; Corcoran, Philip C; Thomas, Marvin L; Clark, Tannia; Lewis, Billeta G; Hoyt, Robert F; Eckhaus, Michael; Pierson, Richard N; Belli, Aaron J; Wolf, Eckhard; Klymiuk, Nikolai; Phelps, Carol; Reimann, Keith A; Ayares, David; Horvath, Keith A

    2016-04-05

    Preventing xenograft rejection is one of the greatest challenges of transplantation medicine. Here, we describe a reproducible, long-term survival of cardiac xenografts from alpha 1-3 galactosyltransferase gene knockout pigs, which express human complement regulatory protein CD46 and human thrombomodulin (GTKO.hCD46.hTBM), that were transplanted into baboons. Our immunomodulatory drug regimen includes induction with anti-thymocyte globulin and αCD20 antibody, followed by maintenance with mycophenolate mofetil and an intensively dosed αCD40 (2C10R4) antibody. Median (298 days) and longest (945 days) graft survival in five consecutive recipients using this regimen is significantly prolonged over our recently established survival benchmarks (180 and 500 days, respectively). Remarkably, the reduction of αCD40 antibody dose on day 100 or after 1 year resulted in recrudescence of anti-pig antibody and graft failure. In conclusion, genetic modifications (GTKO.hCD46.hTBM) combined with the treatment regimen tested here consistently prevent humoral rejection and systemic coagulation pathway dysregulation, sustaining long-term cardiac xenograft survival beyond 900 days.

  13. First successful perinatal management of pregnancy after ABO-incompatible liver transplantation

    PubMed Central

    Higashi, Hisanobu; Obara, Hideaki; Miyakoshi, Kei; Shinoda, Masahiro; Kitago, Minoru; Shimojima, Naoki; Abe, Yuta; Hibi, Taizo; Yagi, Hiroshi; Matsubara, Kentaro; Yamada, Yohei; Itano, Osamu; Hoshino, Ken; Kuroda, Tatsuo; Kitagawa, Yuko

    2017-01-01

    Many papers have reported on pregnancy and delivery after liver transplantation, but there have been no reports on pregnancy after ABO-incompatible liver transplantation. This paper reports the first successful pregnancy and delivery of a newborn after ABO-incompatible liver transplantation for fulminant hepatic failure. The patient was a 39-year-old female. She had an ABO-incompatible liver transplantation, donated from her husband, due to subacute fulminant hepatitis of unknown etiology. She was taking tacrolimus, methylprednisolone, and mizoribine orally for the maintenance of immunosuppression at the time of discharge. She was discharged uneventfully on postoperative day 38 without any rejection episodes. At 1 year and 6 mo after transplantation, she indicated a wish to become pregnant. Therefore, treatment with mycophenolate mofetil was interrupted at that time. After two miscarriages, she finally became pregnant and delivered transvaginally 3 years after the transplantation. All of the pregnancies were conceived naturally. The newborn was female with a birth weight of 3146 g; the Apgar scores were 9 and 10. Delivery was performed smoothly, and the newborn exhibited no malformations. The mother and the newborn were discharged uneventfully. We suggest that pregnancy is possible for recipients after ABO-incompatible liver transplantation. PMID:28210092

  14. Approaches to Managing Autoimmune Cytopenias in Novel Immunological Disorders with Genetic Underpinnings Like Autoimmune Lymphoproliferative Syndrome.

    PubMed

    Rao, V Koneti

    2015-01-01

    Autoimmune lymphoproliferative syndrome (ALPS) is a rare disorder of apoptosis. It is frequently caused by mutations in FAS (TNFRSF6) gene. Unlike most of the self-limiting autoimmune cytopenias sporadically seen in childhood, multi lineage cytopenias due to ALPS are often refractory, as their inherited genetic defect is not going to go away. Historically, more ALPS patients have died due to overwhelming sepsis following splenectomy to manage their chronic cytopenias than due to any other cause, including malignancies. Hence, current recommendations underscore the importance of avoiding splenectomy in ALPS, by long-term use of corticosteroid-sparing immunosuppressive agents like mycophenolate mofetil and sirolimus. Paradigms learnt from managing ALPS patients in recent years is highlighted here and can be extrapolated to manage refractory cytopenias in patients with as yet undetermined genetic bases for their ailments. It is also desirable to develop international registries for children with rare and complex immune problems associated with chronic multilineage cytopenias in order to elucidate their natural history and long-term comorbidities due to the disease and its treatments.

  15. Cutaneous Squamous Cell Carcinomas in Organ Transplant Recipients

    PubMed Central

    Chockalingam, Ramya; Downing, Christopher; Tyring, Stephen K.

    2015-01-01

    Non-melanoma skin cancers represent a major cause of morbidity after organ transplantation. Squamous cell carcinomas (SCC) are the most common cutaneous malignancies seen in this population, with a 65–100 fold greater incidence in organ transplant recipients compared to the general population. In recent years, human papillomaviruses (HPV) of the beta genus have been implicated in the pathogenesis of post-transplant SCCs. The underlying mechanism of carcinogenesis has been attributed to the E6 and E7 proteins of HPV. Specific immunosuppressive medications, such as the calcineurin inhibitors and azathioprine, are associated with a higher incidence of post-transplant SCCs compared to other immunosuppressive agents. Compared to other immunosuppressives, mTOR inhibitors and mycophenolate mofetil have been associated with a decreased risk of developing post-transplant non-melanoma skin cancers. As a result, they may represent ideal immunosuppressive medications in organ transplant recipients. Treatment options for post-transplant SCCs include surgical excision, Mohs micrographic surgery, systemic retinoid therapy, adjunct topical therapy, electrodessication and curettage, and radiation therapy. This review will discuss the epidemiology, risk factors, and management options of post-transplant SCCs. In addition, the underlying mechanisms of beta-HPV mediated carcinogenesis will be discussed. PMID:26239556

  16. Vascular Delivery of rAAVrh74.MCK.GALGT2 to the Gastrocnemius Muscle of the Rhesus Macaque Stimulates the Expression of Dystrophin and Laminin α2 Surrogates

    PubMed Central

    Chicoine, Louis G.; Rodino-Klapac, Louise R.; Shao, Guohong; Xu, Rui; Bremer, William G.; Camboni, Marybeth; Golden, Bethannie; Montgomery, Chrystal L.; Shontz, Kimberly; Heller, Kristin N.; Griffin, Danielle A.; Lewis, Sarah; Coley, Brian D.; Walker, Christopher M.; Clark, K. Reed; Sahenk, Zarife; Mendell, Jerry R.; Martin, Paul T.

    2014-01-01

    Overexpression of GALGT2 in skeletal muscle can stimulate the glycosylation of α dystroglycan and the upregulation of normally synaptic dystroglycan-binding proteins, some of which are dystrophin and laminin α2 surrogates known to be therapeutic for several forms of muscular dystrophy. This article describes the vascular delivery of GALGT2 gene therapy in a large animal model, the rhesus macaque. Recombinant adeno-associated virus, rhesus serotype 74 (rAAVrh74), was used to deliver GALGT2 via the femoral artery to the gastrocnemius muscle using an isolated focal limb perfusion method. GALGT2 expression averaged 44 ± 4% of myofibers after treatment in macaques with low preexisting anti-rAAVrh74 serum antibodies, and expression was reduced to 9 ± 4% of myofibers in macaques with high preexisting rAAVrh74 immunity (P < 0.001; n = 12 per group). This was the case regardless of the addition of immunosuppressants, including prednisolone, tacrolimus, and mycophenolate mofetil. GALGT2-treated macaque muscles showed increased glycosylation of α dystroglycan and increased expression of dystrophin and laminin α2 surrogate proteins, including utrophin, plectin1, agrin, and laminin α5. These experiments demonstrate successful transduction of rhesus macaque muscle with rAAVrh74.MCK.GALGT2 after vascular delivery and induction of molecular changes thought to be therapeutic in several forms of muscular dystrophy. PMID:24145553

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

    PubMed

    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.

  18. [Dermatomyositis-update].

    PubMed

    Volc-Platzer, B

    2015-08-01

    Dermatomyositis is a rare idiopathic inflammatory myopathy that affects adults and children, mostly female. Hallmarks of the disease are myositis with necrosis, regeneration and perifascicular atrophy accompanied by a typical skin rash with heliotrope erythema, Gottron's sign, Gottron's papules and nail fold changes with splinter hemorrhage. Typical skin symptoms may appear 6 months up to 2 years before muscle involvement (amyopathic dermatomyositis). New myositis-specific antibodies may allow clinicoserologic correlations within a heterogeneous clinical spectrum. Autoantibody profiles, subtype of myositis, overlap with other collagen vascular disorders and/or malignancy (paraneoplastic dermatomyositis) as well as age of the patients all have a considerable impact on course and prognosis. Infections, drugs and tumors may trigger activation of T and B cells, plasmacytoid dendritic cells, overproduction of type I interferons and complement-mediated endothelial cell damage resulting in vasculopathy. UV radiation may also trigger dermatomyositis. Oral corticosteroids (1.5-2.0 mg/kg body weight/day) are the mainstay of treatment until improvement of muscle symptoms and/or normalization of muscle enzymes with subsequent slow tapering. Corticosteroids may be given as monotherapy or combined with steroid-sparing immunosuppressive agents' i.e. azathioprine, methotrexate, mycophenolate mofetil or high-dose intravenous immunoglobulins. Prognosis has improved considerably since use of high-dose corticosteroids, from 50 to 90% response rate. New therapies with biologicals (anti-CD20-, anti-TNFalpha-, anti-interferon antibodies) and Janus kinase inhibitors are currently being evaluated.

  19. Prognostic factors for the evolution and reversibility of chronic rejection in pediatric liver transplantation

    PubMed Central

    Tannuri, Ana Cristina Aoun; Lima, Fabiana; de Mello, Evandro Sobroza; Tanigawa, Ryan Yukimatsu; Tannuri, Uenis

    2016-01-01

    OBJECTIVE: Chronic rejection remains a major cause of graft failure with indication for re-transplantation. The incidence of chronic rejection remains high in the pediatric population. Although several risk factors have been implicated in adults, the prognostic factors for the evolution and reversibility of chronic rejection in pediatric liver transplantation are not known. Hence, the current study aimed to determine the factors involved in the progression or reversibility of pediatric chronic rejection by evaluating a series of chronic rejection cases following liver transplantation. METHODS: Chronic rejection cases were identified by performing liver biopsies on patients based on clinical suspicion. Treatment included maintaining high levels of tacrolimus and the introduction of mofetil mycophenolate. The children were divided into 2 groups: those with favorable outcomes and those with adverse outcomes. Multivariate analysis was performed to identify potential risk factors in these groups. RESULTS: Among 537 children subjected to liver transplantation, chronic rejection occurred in 29 patients (5.4%). In 10 patients (10/29, 34.5%), remission of chronic rejection was achieved with immunosuppression (favorable outcomes group). In the remaining 19 patients (19/29, 65.5%), rejection could not be controlled (adverse outcomes group) and resulted in re-transplantation (7 patients, 24.1%) or death (12 patients, 41.4%). Statistical analysis showed that the presence of ductopenia was associated with worse outcomes (risk ratio=2.08, p=0.01). CONCLUSION: The presence of ductopenia is associated with poor prognosis in pediatric patients with chronic graft rejection. PMID:27166772

  20. Optimizing the use of existing therapies in lupus.

    PubMed

    Croyle, Lucy; Morand, Eric F

    2015-02-01

    The management of systemic lupus erythematosus (SLE) is complicated by heterogeneous clinical presentations, a lack of universally accepted tools for the measurement of disease activity and a lack of powerful, safe, specific targeted therapies. Current medical treatment of disease activity relies on glucocorticoids as well as agents including hydroxychloroquine (HCQ), mycophenolate mofetil (MMF) azathioprine (AZA), and less frequently cyclophosphamide. These agents are generally used in fixed, weight-based dosing regimens, and both incomplete response and adverse effects are common. An emerging literature in SLE and other inflammatory diseases in which these drugs are used suggests that improved patient outcomes could be achieved through a different approach to their use. Measurement of drug or metabolite concentrations has been shown in a number of studies to identify under- and over-dosing, predict efficacy and detect non-adherence to therapy, with positive associations between optimum drug or metabolite levels and improved outcomes. In this paper, we will review the literature regarding the measurement of HCQ, MMF, AZA and cyclophosphamide drug and metabolite levels in SLE and inflammatory disease, and make recommendations for future research that could facilitate improved outcomes for patients with SLE.

  1. Rabbit Model of Human Gliomas: Implications for Intra-Arterial Drug Delivery

    PubMed Central

    Qin, Huamin; Janowski, Miroslaw; Pearl, Monica S.; Malysz-Cymborska, Izabela; Li, Shen; Eberhart, Charles G.

    2017-01-01

    The prognosis for malignant brain tumors remains poor despite a combination of surgery, radiotherapy, and chemotherapy. This is partly due to the blood-brain barrier, a major obstacle that prevents therapeutic agents from effectively reaching the tumor. We have recently developed a method for precise and predictable opening of the blood-brain barrier via the intra-arterial administration of mannitol, a hyperosmolar agent, in a rabbit model, whose vascular anatomy facilitates the use of standard interventional neuroradiology techniques and devices. To date, however, no protocols are available that enable human glioma modeling in rabbits. In this article, we report on the xenotransplantation of a human glioblastoma (GBM-1) in adult New Zealand rabbits. We induced multi-drug immunosuppression (Mycophenolate Mofetil, Dexamethasone, Tacrolimus) and stereotactically implanted GBM-1 tumor cells into rabbit brains. The rabbits were followed for 42 days, monitored by MRI and body weight measurements, and underwent postmortem histopathological analysis. On MRI, brain tumors were identified on T2-weighted scans. On histopathology, tumors were detected with hematoxylin/eosin and their human origin was confirmed with immunohistochemistry against human-specific antigens. Our method for human glioma modeling in rabbits provides the foundation to test novel treatment strategies, including intra-arterial therapeutic agent delivery. PMID:28103265

  2. Infections and systemic lupus erythematosus

    PubMed Central

    Skare, Thelma Larocca; Dagostini, Jéssica Scherer; Zanardi, Patricia Imai; Nisihara, Renato Mitsunori

    2016-01-01

    ABSTRACT Objective To determine the incidence of infections in a population of systemic lupus erythematosus individuals and the characteristics of infections regarding original site, as well as to study the possible associations between infections and treatment. Methods An analytical retrospective study using data from medical charts of systemic lupus erythematosus patients from a single university hospital. A total of 144 patients followed up for five years were included. Data collected comprised age of patients and age at onset of lupus, sex and ethnicity, disease duration before the study period, medications, cumulative dose of prednisone, occurrence of infections and their original site. Results The most frequent infections were urinary tract infections (correlated to use of prednisone − p<0.0001 and cyclophosphamide − p=0.045), upper airways infections (correlated to use of prednisone − p=0.0004, mycophenolate mofetil − p=0.0005, and cyclosporine − p=0.025), and pneumonia (associated to prednisone − p=0.017). Conclusion Prednisone was the drug more often associated with presence of infections, pointing to the need for a more judicious management of this drug. PMID:27074234

  3. A single-center study of C1q nephropathy in children.

    PubMed

    Roberti, Isabel; Baqi, Noosha; Vyas, Shefali; Kim, Dae Un

    2009-01-01

    C1q nephropathy (C1qN) is a rare idiopathic glomerulopathy typically seen in adolescents and young adults. All kidney biopsies done from 2002 to 2007 were analyzed (264). Thirteen cases of C1qN from 212 (6.6%) native biopsies and one case out of 52 (1.9%) transplant biopsies were reviewed regarding demographic features, clinical presentation, histopathology, treatment, and outcome. Age varied from 1 to 18 years; half were boys. Ten children (71.4%) presented with nephrotic syndrome (NS). The most common histopathology found was diffuse mesangial proliferative glomerulonephritis (DMP) by light microscopy (LM), with diffuse granular staining for C1q predominantly in the mesangium. Children with either NS or persistent gross hematuria received prednisone and angiotensin-converting enzyme inhibitors (ACEi) (11). Median follow-up was 36 months. Steroid response was complete in 6 patients (54.5%). Those with steroid resistance (5) or steroid dependence (2) received further immunosuppression with mycophenolate mofetil (MMF) or tacrolimus (Tac). Three children achieved complete remission and four partial remission. Frequent relapses were seen in 4/14 patients. Renal survival was 100%. Our report reveals a high incidence of C1qN in pediatric patients, with variable clinical presentation. Despite a high incidence of steroid resistance among those with NS, an excellent response was observed with the addition of further immunosuppression.

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

    PubMed

    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

    2016-11-16

    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.

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

    PubMed

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

    2016-10-04

    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.

  6. Cutaneous vasculitis: diagnosis and management.

    PubMed

    Carlson, J Andrew; Cavaliere, L Frank; Grant-Kels, Jane M

    2006-01-01

    Vasculitis is histologically defined as inflammatory cell infiltration and destruction of blood vessels. Vasculitis is classified as primary (idiopathic, eg, cutaneous leukocytoclastic angiitis, Wegener's granulomatosis) or secondary, a manifestation of connective tissue diseases, infections, adverse drug eruptions, or a paraneoplastic phenomenon. Cutaneous vasculitis, manifested as urticaria, purpura, hemorrhagic vesicles, ulcers, nodules, livedo, infarcts, or digital gangrene, is a frequent and often significant component of many systemic vasculitic syndromes such as lupus or rheumatoid vasculitis and antineutrophil cytoplasmic antibody-associated primary vasculitic syndromes such as Churg-Strauss syndrome. In most instances, cutaneous vasculitis represents a self-limited, single-episode phenomenon, the treatment of which consists of general measures such as leg elevation, warming, avoidance of standing, cold temperatures and tight fitting clothing, and therapy with antihistamines, aspirin, or nonsteroidal anti-inflammatory drugs. More extensive therapy is indicated for symptomatic, recurrent, extensive, and persistent skin disease or coexistence of systemic disease. For mild recurrent or persistent disease, colchicine and dapsone are first-choice agents. Severe cutaneous and systemic disease requires more potent immunosuppression (prednisone plus azathioprine, methotrexate, cyclophosphamide, cyclosporine, or mycophenolate mofetil). In cases of refractory vasculitis, plasmapheresis and intravenous immunoglobulin are viable considerations. The new biologic therapies that work via cytokine blockade or lymphocyte depletion such as tumor alpha inhibitor infliximab and the anti-B-cell antibody rituximab, respectively, are showing benefit in certain settings such as Wegener's granulomatosis, antineutrophil cytoplasmic antibody-associated vasculitis, Behçet's disease, and cryoglobulinemic vasculitis.

  7. Current status of liver transplantation across ABO blood-type barrier.

    PubMed

    Egawa, Hiroto; Ohdan, Hideki; Haga, Hironori; Tsuruyama, Tatsuaki; Oike, Fumitaka; Uemoto, Shinji; Ozawa, Kazue

    2008-01-01

    Outcomes of ABO-blood type incompatible liver transplantation have recently improved owing to various treatments. The typical clinical manifestations of antibody mediated rejection (AMR) are hepatic necrosis and intrahepatic biliary complication (IHBC). The prognosis of AMR is poor. AMR is the result of circulatory disturbance which is caused by injury to the endothelium due to an antibody-antigen-complement reaction. Diffuse C4d staining in the portal capillaries and periportal areas in severe AMR. Since natural antibodies against A/B carbohydrate determinants are likely to develop as a result of exposure to environmental bacteria that express similar determinants, the B-1 lineage has been speculated to be the major population of B-cell types responding to A/B determinants. Calcineurin inhibitors block B-1 cell differentiation. Rituximab can be used to deplete both cells that are producing IgM antibodies and those that have already differentiated into B-1 cells. Mycophenolate mofetil is required to inhibit the production of IgG subclass of antibodies. The outcome is now similar to that of blood-type-matched transplantation. However, there are still issues to be solved in order to further improve the outcome via a decrease of infection.

  8. Hypertrophic pachymeningitis associated with cerebral spinal fluid hypovolemia as initial presentation of systemic lupus erythematous.

    PubMed

    Sanchez-Garcia, Me; Gomez-Delgado, F; Gomez-Garduño, A; Blanco-Molina, A; Puebla, Ra Fernandez de la

    2014-02-01

    We report a case of a 61-year-old man with thickening of the dura mater associated with the presence of subdural collections as a consequence of cerebral spinal fluid hypovolemia (CSFH) and hypertrophic pachymeningitis (HP) as presentation of systemic lupus erythematous (SLE). The patient complained about fatigue, musculoskeletal pain, headache and skin lesions. In the laboratory tests minimal normocytic anemia, mild leukopenia, polyclonal hypergammaglobulinemia and antinuclear antibodies (ANA), anti-double-stranded DNA antibodies (dsDNA), antibodies against extractable nuclear antigens (ENA) type SSA-Ro, anti-Smith antigen antibodies (anti-Sm) and anti-ribonucleoprotein antibodies (anti-RNP) were detected. Cranial magnetic resonance imaging (MRI), with and without gadolinium enhancement, revealed generalized thickening of the dura mater more severe at the right parieto-occipital lobes with the presence of subdural collections. The patient was diagnosed with SLE associated both with CSFH and HP. A conservative treatment with prednisone 60 mg daily, mycophenolate mofetil (MMF) 1 g daily and hydroxychloroquine 200 mg twice a day was started with significant clinical and radiological improvement (almost complete resolution of the subdural collections and clear decrease of meningeal thickness). The authors emphasize that HP associated with CSFH in the context of SLE is a rare entity, which makes this case unique.

  9. CD40-mediated NFκB activation in B cells is increased in multiple sclerosis and modulated by therapeutics1

    PubMed Central

    Chen, Ding; Ireland, Sara J.; Remington, Gina; Alvarez, Enrique; Racke, Michael K.; Greenberg, Benjamin; Frohman, Elliot M.; Monson, Nancy L.

    2017-01-01

    CD40 interacts with CD40 ligand and plays an essential role in immune regulation and homeostasis. Recent research findings, however, support a pathogenic role of CD40 in a number of autoimmune diseases. We previously showed that memory B cells from relapsing-remitting multiple sclerosis (RRMS) patients exhibited enhanced proliferation with CD40 stimulation compared to healthy donors. In this study, we used a multi-parameter phosflow approach to analyze the phosphorylation status of NFκB and three major MAP kinases (P38, ERK and JNK), the essential components of signaling pathways downstream of CD40 engagement in B cells from MS patients. We found that memory and naïve B cells from RRMS and secondary progressive MS (SPMS) patients exhibited a significantly elevated level of phosphorylated NFκB (p-P65) following CD40 stimulation compared to healthy donor controls. Combination therapy with interferon beta-1a (Avonex) and mycophenolate mofetil (Cellcept) modulated the hyper-phosphorylation of P65 in B cells of RRMS patients at levels similar to healthy donor controls. Lower disease activity after the combination therapy correlated with the reduced phosphorylation of P65 following CD40 stimulation in treated patients. In addition, glatiramer acetate (GA) treatment also significantly reduced CD40-mediated P65 phosphorylation in RRMS patients, suggesting that reducing CD40-mediated p-P65 induction may be a general mechanism by which some current therapies modulate MS disease. PMID:27798157

  10. Recurrent Psoriasis After Introduction of Belatacept in 2 Kidney Transplant Recipients.

    PubMed

    Cicora, Federico; Roberti, Javier

    2016-06-01

    Organ transplant recipients may have skin diseases as a result of immunosuppression, but psoriasis is reported infrequently. This skin condition may be induced by immunosuppression imbalance. We present 2 cases of recurrent psoriasis in 2 kidney transplant patients with belatacept-based immunosuppressive regimens. Two years after transplant, upon suspicion of calcineurin inhibitor neurotoxicity in the first patient, tacrolimus was replaced with belatacept. The patient's neurological signs resolved but the patient presented with skin lesions compatible with psoriatic plaques, successfully treated with betamethasone dipropionate and hydrocortisone. The second patient had a history of obesity and dyslipidemia, left foot amputation, and psoriasis. He received a kidney transplant, and maintenance immunosuppression included prednisone, mycophenolate mofetil, and belatacept. At posttransplant month 15, the patient presented with cutaneous erythematosus, maculopapular, and desquamative lesions compatible with psoriasis, treated with betamethasone dipropionate. The belatacept-based immunosuppressive regimens were maintained and psoriasis resolved. Psoriasis is a potential complication in kidney recipients that may recur when belatacept is used and/or tacrolimus is withdrawn as it could have happened in the first patient. The characteristics of the second case may suggest that belatacept might not have been the inciting agent. Good results were obtained with topical treatment.

  11. The case for pancreas after kidney transplantation.

    PubMed

    Fridell, Jonathan A; Mangus, Richard S; Hollinger, Edward F; Taber, Tim E; Goble, Michelle L; Mohler, Elaine; Milgrom, Martin L; Powelson, John A

    2009-01-01

    Pancreas after kidney (PAK) transplantation has historically demonstrated inferior pancreas allograft survival compared to simultaneous pancreas and kidney (SPK) transplantation. Under our current immunosuppression protocol, we have noted excellent outcomes and rare immunological graft loss. The goal of this study was to compare pancreas allograft survival in PAK and SPK recipients using this regimen. This was a single center retrospective review of all SPK and PAK transplants performed between January 2003 and November 2007. All transplants were performed with systemic venous drainage and enteric exocrine drainage. Immunosuppression included induction with rabbit anti-thymocyte globulin (thymoglobulin), early steroid withdrawal, and maintenance with tacrolimus and sirolimus or mycophenolate mofetil. Study end points included graft and patient survival and immunosuppression related complications. Transplants included PAK 61 (30%) and SPK 142 (70%). One-yr patient survival was PAK 98% and SPK 95% (p = 0.44) and pancreas graft survival was PAK 95% and SPK 90% (p = 0.28). Acute cellular rejection was uncommon with 2% requiring treatment in each group. Survival for PAK using thymoglobulin induction, early steroid withdrawal and tacrolimus-based immunosuppression is at least comparable to SPK and should be pursued in the recipient with a potential living donor.

  12. Chimeric 2C10R4 anti-CD40 antibody therapy is critical for long-term survival of GTKO.hCD46.hTBM pig-to-primate cardiac xenograft

    PubMed Central

    Mohiuddin, Muhammad M.; Singh, Avneesh K.; Corcoran, Philip C.; Thomas III, Marvin L.; Clark, Tannia; Lewis, Billeta G.; Hoyt, Robert F.; Eckhaus, Michael; Pierson III, Richard N.; Belli, Aaron J.; Wolf, Eckhard; Klymiuk, Nikolai; Phelps, Carol; Reimann, Keith A.; Ayares, David; Horvath, Keith A.

    2016-01-01

    Preventing xenograft rejection is one of the greatest challenges of transplantation medicine. Here, we describe a reproducible, long-term survival of cardiac xenografts from alpha 1-3 galactosyltransferase gene knockout pigs, which express human complement regulatory protein CD46 and human thrombomodulin (GTKO.hCD46.hTBM), that were transplanted into baboons. Our immunomodulatory drug regimen includes induction with anti-thymocyte globulin and αCD20 antibody, followed by maintenance with mycophenolate mofetil and an intensively dosed αCD40 (2C10R4) antibody. Median (298 days) and longest (945 days) graft survival in five consecutive recipients using this regimen is significantly prolonged over our recently established survival benchmarks (180 and 500 days, respectively). Remarkably, the reduction of αCD40 antibody dose on day 100 or after 1 year resulted in recrudescence of anti-pig antibody and graft failure. In conclusion, genetic modifications (GTKO.hCD46.hTBM) combined with the treatment regimen tested here consistently prevent humoral rejection and systemic coagulation pathway dysregulation, sustaining long-term cardiac xenograft survival beyond 900 days. PMID:27045379

  13. Risk factors of acute kidney injury after orthotopic liver transplantation in China

    PubMed Central

    Zongyi, Yin; Baifeng, Li; Funian, Zou; Hao, Li; Xin, Wang

    2017-01-01

    In this study, we determined the risk factors for acute kidney injury (AKI) following orthotopic liver transplantation (OLT) in China. We collected 5074 donation after cardiac death (DCD) OLT recipients who underwent surgery between January 1, 2010, and December 31, 2015, in 86 academic hospitals or transplant centers in China. Univariate and multivariate analyses were used to investigate the criticality of donor, graft, or recipient variables in the development of post-OLT AKI. In all, 4482 patients were included (median age, 49.31 years). Post-OLT AKI occurred in 3.97% patients, and 73.6% of all OLT patients were male. The 1- and 5-year cumulative survival rates (CSRs) of the AKI group were 33.95% and 25.24%, respectively, compared with 86.34% and 70.05%, respectively, of the non-AKI group (P < 0.001). The independent risk factors for post-OLT AKI were blood loss, cold ischemia time, warm ischemia time, preoperative serum creatinine, the treatment period with dopamine, overexposure to calcineurin inhibitor, and combined mycophenolate mofetil use (P < 0.05). These had a high prediction accuracy for post-OLT AKI (area under the curve [AUC] = 0.740). PMID:28134286

  14. Comparison of Non-myeloablative Conditioning Regimens for Lymphoproliferative Disorders

    PubMed Central

    Hong, Sanghee; Le-Rademacher, Jennifer; Artz, Andrew; McCarthy, Philip L.; Logan, Brent R.; Pasquini, Marcelo C.

    2014-01-01

    Hematopoietic cell transplantation (HCT) with non-myeloablative conditioning (NMA) for lymphoproliferative diseases (LD) includes fludarabine with and without low-dose total body irradiation (TBI). Transplant outcomes were compared among patients ≥40 years with LD who received a HCT with TBI (N=382) and no-TBI (N=515) NMA from 2001 to 2011. The groups were comparable except for donor, graft, prophylaxis for graft-versus-host disease (GVHD), disease status and year of HCT. Cumulative incidences of grades II–IV GVHD at 100 days, were 29% and 20% (p=0.001), and chronic GVHD at 1 year were 54% and 44% (p=0.004) for TBI and no-TBI, respectively. Multivariate analysis of progression/relapse, treatment failure and mortality showed no outcome differences by conditioning. Full donor chimerism at day 100 was observed in 82% vs. 64% in the TBI and no-TBI groups, respectively (p=0.006). Subset of four most common conditioning/ GVHD prophylaxis combinations demonstrated higher rates of grades II–IV acute (p<0.001) and chronic GVHD (p<0.001) among recipients of TBI-mycophenolate mofetil (MMF) compared to other combinations. TBI-based NMA conditioning induces faster full donor chimerism but overall survival outcomes are comparable to no-TBI regimens. Combination of TBI and MMF are associated with higher rates of GVHD without impact on survival outcomes in patients with LD. PMID:25437248

  15. SLE and Tuberculosis: A Case Series and Review of Literature

    PubMed Central

    Jamil, Md; Roy, Aakash; Talukdar, Kishore Kumar

    2017-01-01

    Systemic Lupus Erythematosus (SLE) and Tuberculosis (TB) are intricately related with an increase in the risk of TB in SLE. Primary mechanisms pertaining to the increased susceptibility for TB are the inherent immunodeficient state of SLE and use of immunosuppressant agents in the treatment of SLE. We report a case series of five female patients of SLE with TB who presented between January 2015 and December 2015 in a tertiary care teaching hospital in North Eastern India. All the patients were young to middle aged females having SLE with or without lupus nephritis who were on immunosuppressive therapy with corticosteroids, mycophenolate mofetil or cyclophosphamide. Two of the cases had sputum positive pulmonary tuberculosis while rest had Extra-Pulmonary TB (EPTB). The response to anti-tubercular therapy led to clinical improvement in all the cases except one who had an adverse outcome. Our series further substantiates the increased risk of TB in SLE thus, prompting further research towards better management of these two disease entities in conjunction.

  16. Clinicopathological insights into lupus glomerulonephritis in Japanese and Asians.

    PubMed

    Yokoyama, Hitoshi; Okuyama, Hiroshi; Yamaya, Hideki

    2011-06-01

    Lupus nephritis comprises a spectrum of glomerular, vascular, and tubulointerstitial lesions, which has significant racial variation in severity and manifestations. The current classification (ISN/RPS 2003) has been improved successfully for the categorization of lupus glomerulonephritis (LGN). On the basis of this classification, 480 Japanese cases revealed the following distribution: class I 3%, class II 16%, class III 13%, class IV-S 11%, class IV-G 41%, class V 16%, and class VI 1%. Class IV-G with chronicity tended to have the worst renal outcome. Nephrotic syndrome was a more frequent complication in class IV-S (50%), class IV-G (72%), and class V (56%), with poor renal and actuarial outcomes. With regard to therapy, treatment options including glucocorticoids alone or combined with antimetabolites (azathioprine, mizoribine, mycophenolate mofetil), calcineurin inhibitors (cyclosporine A, tacrolimus), or alkylating agents (intravenous cyclophosphamide injection) improved the outcome of LGN; however, there is no high-grade clinical evidence from Japan. Further studies are needed to resolve the clinicopathological problems of LGN, especially IV-S, IV-G, and pure membranous lupus nephritis in Japanese patients.

  17. [Lupus nephritis: up-to-date].

    PubMed

    Karras, A

    2015-02-01

    Renal involvement is frequent during natural history of systemic lupus erythematosus (SLE) and has a major prognostic value in this systemic disease. Screening for renal symptoms, such as proteinuria, micro-haematuria or renal failure must be performed at initial diagnosis and repeated during subsequent follow-ups. Any significant abnormality of these parameters may reveal active glomerulonephritis (GN) and should lead to a renal biopsy, which will significantly impact the therapeutic choices. Proliferative GN, defined as class III or IV by the actual histo-pathological classification, is the most severe form of SLE-associated nephropathy and can lead to end-stage renal disease (ESRD) in up to 60% of cases, according to ethnicity and follow-up duration. Standard induction treatment of active proliferative GN includes corticosteroids combined with an immunosuppressive drug, which can either be cyclophosphamide or mycophenolate mofetil (MMF). Even though, recent biotherapies have not yet proved their efficacy in the field of lupus nephritis, new protocols are expected, aiming higher remission rates and avoidance of high-dose corticosteroids regimens. When remission is achieved in proliferative GN, a maintenance therapy is required to decrease the risk of relapse, using either azathioprine or MMF. Immunosuppressive drugs are responsible for an increased risk of infectious or neoplastic complications but cardiovascular disease is actually one of the main causes of mortality among lupus patients, especially for patients with SLE-related kidney disease, well before reaching ESRD.

  18. Lack of benefit of early protocol biopsies in renal transplant patients receiving TAC and MMF: a randomized study.

    PubMed

    Rush, D; Arlen, D; Boucher, A; Busque, S; Cockfield, S M; Girardin, C; Knoll, G; Lachance, J-G; Landsberg, D; Shapiro, J; Shoker, A; Yilmaz, S

    2007-11-01

    We conducted a randomized, multicenter study to determine whether treatment of subclinical rejection with increased corticosteroids resulted in beneficial outcomes in renal transplant patients receiving tacrolimus (TAC), mycophenolate mofetil (MMF) and prednisone. One hundred and twenty-one patients were randomized to biopsies at 0,1,2,3 and 6 months (Biopsy arm), and 119 to biopsies at 0 and 6 months only (Control arm). The primary endpoint of the study was the prevalence of the sum of the interstitial and tubular scores (ci + ct)> 2 (Banff) at 6 months. Secondary endpoints included clinical and subclinical rejection and renal function. At 6 months, 34.8% of the Biopsy and 20.5% of the Control arm patients had a ci + ct score >or= 2 (p = 0.07). Between months 0 and 6, clinical rejection episodes were 12 in 10 Biopsy arm patients and 8 in 8 Control arm patients (p = 0.44). Overall prevalence of subclinical rejection in the Biopsy arm was 4.6%. Creatinine clearance at 6 months was 72.9 +/- 21.7 in the Biopsy and 68.90 mL/min +/- 18.35 mL/min in the Control arm patients (p = 0.18). In conclusion, we found no benefit to the procurement of early protocol biopsies in renal transplant patients receiving TAC, MMF and prednisone, at least in the short term. This is likely due to their low prevalence of subclinical rejection.

  19. Therapeutic interventions of tissue specific autoimmune onset in systemic lupus erythematosus.

    PubMed

    Dasgupta, Subhajit; Dasgupta, Shaoni

    2016-06-10

    Systemic lupus erythematosus (lupus) is a female predominant autoimmune disease. The auto reactive B cells and T helper cells together are known to develop self-reactive immune responses in different tissues like kidney, bone, cardiovascular and central nervous system. Progression of disease is associated with deposition of immune complex which initiates tissue damage. The therapy for lupus still includes corticosteroids to reduce allergic manifestations and inflammatory immune responses. Recent observations suggested that, mycophenolate mofetil and cyclophosphamide treatment in combination with corticosteroids have benefit in lupus therapy. The prospect of B cell depletion by CD20 targeted monoclonal antibody Rituximab has been demonstrated in lupus patients. The CD52 specific monoclonal antibody Alemtuzumab is another proposition for lupus therapy. The drug Belimumab inhibits B cell activation by altering BAFF/APRIL signal cascade. Recent discovery of the CD22 targeted Epratuzumab also shows therapeutic prospect. The researches on new generation drugs for autoimmune lupus include search for inhibitors of CD40-CD40Ligand interactions, CD86 activation, selective modulation of complement cascades. The choice of inhibitors of transcription factor NF-κBp65 and selective modulators for estrogen receptor alpha are proposed areas of lupus drug discovery research. Keeping a close eye on the mechanisms of disease onset, a comprehensive view is provided on recent therapy of systemic lupus erythematosus.

  20. Systemic lupus erythematosus.

    PubMed

    Kaul, Arvind; Gordon, Caroline; Crow, Mary K; Touma, Zahi; Urowitz, Murray B; van Vollenhoven, Ronald; Ruiz-Irastorza, Guillermo; Hughes, Graham

    2016-06-16

    Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect many organs, including the skin, joints, the central nervous system and the kidneys. Women of childbearing age and certain racial groups are typically predisposed to developing the condition. Rare, inherited, single-gene complement deficiencies are strongly associated with SLE, but the disease is inherited in a polygenic manner in most patients. Genetic interactions with environmental factors, particularly UV light exposure, Epstein-Barr virus infection and hormonal factors, might initiate the disease, resulting in immune dysregulation at the level of cytokines, T cells, B cells and macrophages. Diagnosis is primarily clinical and remains challenging because of the heterogeneity of SLE. Classification criteria have aided clinical trials, but, despite this, only one drug (that is, belimumab) has been approved for use in SLE in the past 60 years. The 10-year mortality has improved and toxic adverse effects of older medications such as cyclophosphamide and glucocorticoids have been partially offset by newer drugs such as mycophenolate mofetil and glucocorticoid-sparing regimes. However, further improvements have been hampered by the adverse effects of renal and neuropsychiatric involvement and late diagnosis. Adding to this burden is the increased risk of premature cardiovascular disease in SLE together with the risk of infection made worse by immunosuppressive therapy. Challenges remain with treatment-resistant disease and symptoms such as fatigue. Newer therapies may bring hope of better outcomes, and the refinement to stem cell and genetic techniques might offer a cure in the future.

  1. The impact of surveillance and rapid reduction in immunosuppression to control BK virus-related graft injury in kidney transplantation.

    PubMed

    Elfadawy, Nissreen; Flechner, Stuart M; Liu, Xiaobo; Schold, Jesse; Tian, Devin; Srinivas, Titte R; Poggio, Emilio; Fatica, Richard; Avery, Robin; Mossad, Sherif B

    2013-08-01

    We prospectively screened 609 consecutive kidney (538) and kidney-pancreas (71) transplant recipients for BK viremia over a 4-year interval using polymerase chain reaction viral load detection and protocol kidney biopsies. We found that BK viremia is common at our center: total cases 26.7%, cases during first year 21.3% (mean 4 months), and recipients with ≥ 10 000 copies/ml 12.3%. We found few predictive clinical or demographic risk factors for any BK viremia or viral loads ≥ 10,000 copies/ml, other than prior treatment of biopsy confirmed acute rejection and/or higher immunosuppressive blood levels of tacrolimus (P = 0.001) or mycophenolate mofetil (P = 0.007). Viral loads at diagnosis (<10 000 copies/ml) demonstrated little impact on graft function or survival. However, rising copy numbers demand early reductions in immunosuppressive drug doses of at least 30-50%. Viral loads >185 000 copies/ml at diagnosis were predictive of BK virus-associated nephropathy (BKVAN; OR: 113.25, 95% CI: 17.22-744.6, P < 0.001). Surveillance for BK viremia and rapid reduction of immunosuppression limited the incidence of BKVAN to 1.3%. The addition of leflunomide or ciprofloxacin to immunosuppressive dose reduction did not result in greater rates of viral clearance. These data support the role of early surveillance for BK viremia to limit the impact on transplant outcome, although the most effective schedule for screening awaits further investigation.

  2. Approaches to Managing Autoimmune Cytopenias in Novel Immunological Disorders with Genetic Underpinnings Like Autoimmune Lymphoproliferative Syndrome

    PubMed Central

    Rao, V. Koneti

    2015-01-01

    Autoimmune lymphoproliferative syndrome (ALPS) is a rare disorder of apoptosis. It is frequently caused by mutations in FAS (TNFRSF6) gene. Unlike most of the self-limiting autoimmune cytopenias sporadically seen in childhood, multi lineage cytopenias due to ALPS are often refractory, as their inherited genetic defect is not going to go away. Historically, more ALPS patients have died due to overwhelming sepsis following splenectomy to manage their chronic cytopenias than due to any other cause, including malignancies. Hence, current recommendations underscore the importance of avoiding splenectomy in ALPS, by long-term use of corticosteroid-sparing immunosuppressive agents like mycophenolate mofetil and sirolimus. Paradigms learnt from managing ALPS patients in recent years is highlighted here and can be extrapolated to manage refractory cytopenias in patients with as yet undetermined genetic bases for their ailments. It is also desirable to develop international registries for children with rare and complex immune problems associated with chronic multilineage cytopenias in order to elucidate their natural history and long-term comorbidities due to the disease and its treatments. PMID:26258116

  3. Monoclonal gammopathy of undeterminated significance and endoneurial IgG deposition

    PubMed Central

    Mathis, Stéphane; Franques, Jérôme; Richard, Laurence; Vallat, Jean-Michel

    2016-01-01

    Abstract Background: Monoclonal gammopathy of undeterminated significance is the most common form of plasma cell dyscrasia, usually considered as benign. In rare cases it may have a malignant course, sometimes limited to an organ such as peripheral nerves. Methods: We describe clinical, electrophysiological and pathological findings in a patient presenting a immunoglobulin G (IgG) paraproteinemic polyneuropathy clinically mimicking a chronic inflammatory demyelinating polyneuropathy. Results: Immuno-electron microscopy (immune-EM) demonstrated that the widenings of the myelin lamellae resulted from the infiltration of IgG between a significant number of myelin lamellae (with absence of inflammatory cells in the epineurium, endoneurium, and perineurium, and the lack signs of vasculitis). This patient was finally treated successfully with lenalidomide then mycophenolate mofetil. Conclusions: In polyneuropathies associated to a monoclonal gammopathy, a nerve biopsy may clinch the diagnosis. Immuno-EM may be required to determine the role of the pathological immunoglobulin in the destruction of the peripheral nerve parenchyma. Diagnosis of such a direct involvement of peripheral nerve can endorse more aggressive treatment of real efficiency. PMID:27603395

  4. Autoimmune polyendocrine syndrome type 1: Utility of KCNRG autoantibodies as a marker of active pulmonary disease and successful treatment with rituximab.

    PubMed

    Popler, Jonathan; Alimohammadi, Mohammad; Kämpe, Olle; Dalin, Frida; Dishop, Megan K; Barker, Jennifer M; Moriarty-Kelsey, Margaret; Soep, Jennifer B; Deterding, Robin R

    2012-01-01

    Autoimmune polyendocrine syndrome type 1 (APS-1), also known as Autoimmune Polyendocrinopathy Candidiasis and Ectodermal Dysplasia (APECD) is a disorder caused by mutations in the autoimmune regulator (AIRE) gene. In some APS-1 patients, significant pulmonary disease is observed. Autoantibodies directed against the potassium channel regulatory protein (KCNRG), found in epithelial cells of terminal bronchioles, have been suggested as a marker for pulmonary disease in APS-1 patients. We report two patients with APS-1; one with and one without lung disease. Patient 1 had multiple admissions for pneumonia and respiratory insufficiency, required non-invasive ventilation, and had findings of bronchiectasis on thoracic imaging and significant lymphocytic infiltrates of the airways on lung biopsy. To verify the autoimmune cause of pulmonary symptoms APS-1 patients, both were tested in a blinded manner for the presence of autoantibodies to KCNRG in serum. We found that only Patient 1 had autoantibodies present. Additionally, Patient 1 had progressive disease despite treatment with several immunomodulating agents, including corticosteroids, azathioprine, and mycophenolate. Patient 1 had a lung biopsy performed which was consistent with B cell lymphocytic aggregates. Rituximab treatment was initiated with apparent good response. This report illustrates the practical use of KCNRG autoantibodies to identify APS-1 patients with pulmonary risk and the successful use of the monoclonal antibody, Rituximab, to treat pulmonary disease in APS-1 patients.

  5. Characteristics of azathioprine use and cessation in a longitudinal lupus cohort

    PubMed Central

    Croyle, Lucy; Hoi, Alberta; Morand, Eric F

    2015-01-01

    Objective Guidelines for azathioprine (AZA) use in systemic lupus erythematosus (SLE), including indications for initiation and cessation, are lacking. Clinical decision-making could be improved if reasons for cessation of AZA treatment were standardised. Methods We determined the characteristics of AZA use in a cohort of patients with SLE and evaluated reasons for AZA cessation. Patients with SLE in a single centre had longitudinal recording of disease activity (Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI)-2k), laboratory investigations and treatment from 2007 to 2012. Results Of 183 patients studied, 67 used AZA on at least one occasion. There was no significant difference between AZA users and non-users in age or American College of Rheumatology criteria. Compared with those not treated with AZA, patients treated with AZA had higher disease activity (time-adjusted mean SLEDAI 5.2±0.3 vs 3.8±0.3, p=0.0028) and damage (Systemic Lupus International Collaborating Clinics (SLICC)-SDI 1.6±0.3 vs 1.2±0.1, p=0.0445), and were more likely to have a positive dsDNA (p=0.0130) and receive glucocorticoids (p<0.0001). AZA therapy was ceased in 30/67 (45%) patients. The predominant reasons for cessation were treatment de-escalation 14 (47%), treatment failure 12 (40%) and toxicity 3 (10%). AZA was switched to mycophenolate mofetil (MMF) in 9/12 (75%) of treatment failures, and this choice was strongly associated with active lupus nephritis. Conclusions AZA toxicity was uncommon, and many patients ceased therapy in the context of treatment de-escalation. However, the frequent development of active lupus nephritis requiring MMF suggests the need to distinguish refractoriness, under-treatment and non-adherence to AZA in patients with SLE. These findings suggest that future studies of AZA metabolite measurement could prove valuable in the management of SLE. PMID:26322237

  6. Stroke Treatments

    MedlinePlus

    ... the base of the aneurysm. Treatment to Maximize Recovery Your medical professional can tell you which treatment ... important in helping you achieve the best possible recovery and independence. A number of types of therapy ...

  7. [Headache Treatment].

    PubMed

    Diener, Hans Christoph; Holle-Lee, Dagny; Nägel, Steffen; Gaul, Charly

    2017-03-01

    A precondition for the successful treatment of headaches is the correct headache diagnosis. Triptans are effective for attack treatment of migraine and cluster headache. However, there are not effective for the treatment of tension-type headache. For the prevention of frequent episodic migraine betablockers, flunarizine, topiramate and amitriptyline are recommended. For the prevention of chronic migraine evidence is only available for onabotulinumtoxinA and topiramate. For prophylactic treatment of tension-type headaches tricyclic antidepressants are used. In cluster headache verapamil (in combination with steroids) is the most frequently used prophylactic agent. This article focusses on the current acute and prophylactic treatment of common headache syndromes.

  8. Hepatotoxicity and liver enzyme alteration in patients with immunobullous diseases receiving immunosuppressive therapy.

    PubMed

    Shahshahani, Mostafa M; Azizahari, Sahar; Soori, Tahere; Manavi, Saeed; Balighi, Kamran; Daneshpazhooh, Maryam; Davatchi, Cheida S; Esmaili, Nasife

    2011-12-01

    To avoid complications of high dose corticosteroid, pemphigus patients are usually co-treated with other immunosuppressive agents. Liver enzyme abnormality occurs commonly during treatment and occasionally causes discontinuation of drugs. To assess the rate of therapy-induced hepatotoxicity in patients with immunobullous diseases, we conducted a study of 250 pemphigus patients under immunosuppressive therapy prospectively. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) plasma levels were recorded before the start of treatment and every week under treatment (up to 3 weeks). Hepatotoxicity was defined as the rise in the ALT plasma levels to greater than twice the upper normal limit. Approximately 81% of patients received prednisolone and azathioprine. Approximately 12% received only prednisolone. Hepatotoxicity occurred in 2.9% (n = 8) of patients after 1 week, in 7.8% (n = 20) after 2 weeks and in 11.5% (n = 29) after 3 weeks. No patient had jaundice or other clinical manifestations of hepatitis. The mean values of ALT and AST before the start of treatment were 20.7 ± 13.7 and 17.6 ± 10.8 U/L, respectively that grew to 47.5 ± 28.5 and 26.8 ± 14.5 U/L, 3 weeks after the initiation of treatment. Distribution of changes was not significantly different among groups of age, sex, immunosuppressive drugs and isoniazid consumption. Under usual treatment of pemphigus, hepatotoxicity occurs in 10% of patients during the first 3 weeks of therapy that does not seem to be associated with azathioprine or mycophenolate mofetil exclusively. High doses of prednisolone may play a role.

  9. Lung Transplant Recipient with Pulmonary Alveolar Proteinosis

    PubMed Central

    Hahn, M. Frances; Abdelrazek, Hesham; Patel, Vipul J.; Walia, Rajat

    2016-01-01

    Pulmonary alveolar proteinosis (PAP) is a progressive lung disease characterized by accumulated surfactant-like lipoproteinaceous material in the alveoli and distal bronchioles. This accumulation is the result of impaired clearance by alveolar macrophages. PAP has been described in 11 solid organ transplant recipients, 9 of whom were treated with mammalian target of rapamycin inhibitors. We report a case of a lung transplant recipient treated with prednisone, mycophenolate mofetil (MMF), and tacrolimus who ultimately developed PAP, which worsened when MMF was replaced with everolimus. PMID:27213073

  10. Clinical Lessons to Be Learned from Patients Developing Chronic Myeloid Leukemia While on Immunosuppressive Therapy after Solid Organ Transplantation: Yet Another Case after Orthotopic Heart Transplantation

    PubMed Central

    Oberender, Christian; Kleeberg, Lorenz; Nienhues, Nicola; Dörken, Bernd; Riess, Hanno

    2014-01-01

    Chronic myeloid leukemia developing after transplantation of solid organs and concomitant immunosuppression is a rare but still significant clinical phenomenon. We here describe an additional case of a 62-year-old male patient developing CML after orthotopic heart transplantation and medication with cyclosporine A, mofetil-mycophenolate, and steroids. Initial antileukemic therapy was imatinib at a standard dose and within 15 months of therapy a complete cytogenetic response was noted. In this report we discuss the clinical implications of these rare but biologically important cases. PMID:25478254

  11. Reversible encephalopathy associated with tacrolimus in pediatric renal transplants.

    PubMed

    Parvex, P; Pinsk, M; Bell, L E; O'Gorman, A M; Patenaude, Y G; Gupta, I R

    2001-07-01

    Neurological complications post transplant have been described with the use of calcineurin inhibitors. Although tacrolimus may be a better immunosuppressant than cyclosporine, its neurological side effects may be worse. Two children, living-related kidney transplant recipients, were treated with antibody induction, mycophenolate mofetil, prednisone, and tacrolimus. Soon after transplant, they each developed an encephalopathy, which when visualized by magnetic resonance imaging showed that it affected both white and grey matter of the brain. Although the encephalopathy was associated with the use of tacrolimus, there was a complete neurological recovery without cessation of the drug.

  12. "Half-half" blisters in bullous pemphigoid successfully treated with adjuvant high-dose intravenous immunoglobulin.

    PubMed

    Pacheco, David; Lopes, Leonor; Soares-Almeida, Luis; Marques, Manuel Sacramento; Filipe, Paulo

    2012-09-01

    Bullous pemphigoid is a rare, autoimmune blistering disease. Its clinical presentation is tense blisters that may arise on normal-appearing or erythematous skin. Bullous pemphigoid refractory to systemic corticosteroids in combination with immunosuppressants such as azathioprine and mycophenolate mofetil may benefit from adjuvant high-dose intravenous immunoglobulin (IVIg). We describe a particular case with an unusual clinical presentation unresponsive to systemic corticosteroids plus azathioprine, in which the addition of high-dose IVIg was successful. The combined therapy of systemic corticosteroids and azathioprine plus high-dose IVIg can be an option in refractory cases due to its efficiency and tolerability.

  13. Should we consider MMF therapy after rituximab for nephrotic syndrome?

    PubMed

    Filler, Guido; Huang, Shih-Han Susan; Sharma, Ajay P

    2011-10-01

    The management of steroid-dependent nephrotic syndrome, especially in patients who have failed to respond to cytotoxic drugs, such as cyclophosphamide, remains challenging. Rituximab represents a new (off-label) therapeutic option. In a significant portion of patients, it has a short serum half-life following the recovery of CD20-positive cells. The addition of mycophenolate mofetil (MMF) as a maintenance therapy is also an attractive option, but one which requires testing in a prospective randomized clinical trial with therapeutic drug monitoring and mechanistic ancillary studies.

  14. Atopic dermatitis: Kids are not just little people.

    PubMed

    Awasthi, Smita; Rothe, Marti Jill; Eichenfield, Lawrence F

    2015-01-01

    The approach to children and adults with atopic dermatitis is similar. In both age groups, failure to respond to conventional therapy should prompt evaluation for complicating factors such as secondary infection and secondary ACD. Immunologic, metabolic, genetic, and nutritional disorders should be considered in the differential diagnosis of refractory pediatric atopic dermatitis. Cutaneous T cell lymphoma (CTCL), cutaneous drug reactions, other spongiotic dermatoses, psoriasis, dermatomycosis, and infestations should be considered in the differential of refractory atopic dermatitis in adults. Systemic therapies prescribed to both children and adults with severe atopic dermatitis include oral corticosteroids, cyclosporine, methotrexate, azathioprine, and mycophenolate mofetil.

  15. [Problems with immunosuppressive agents in nephropathies with chronic renal failure].

    PubMed

    Savoldi, S; Mesiano, P; Rocchietti, M

    2008-01-01

    Immunosuppressive treatment is widely used in transplant patients, who often have chronic renal failure, while its use in nephropathies of native kidneys with chronic renal insufficiency is still limited. In recent years a number of papers have reported advantages of its use also in this setting. A prerequisite for immunosuppression in this condition is accurate renal histology, in order to define the etiology, activity/chronicity index and prognosis. Although clinicians agree on the use of aggressive treatment for secondary nephropathies, the approach to primary forms in the presence of chronic renal failure remains controversial, as does the definition of a ''point of no return'' beyond which treatment could be ineffective or unsafe. Nonrandomized studies found that immunosuppressive drugs such as cyclophosphamide can be useful in membranous nephropathy with renal insufficiency. The use of immunosuppressive drugs in IgA nephropathy in the presence of established renal insufficiency seems to improve renal survival with a limited occurrence of side effects. Since the pharmacokinetics of the current immunosuppressive agents (steroids, azathioprine, cyclophosphamide, chlorambucil, mycophenolate mofetil) is modified by renal insufficiency, attention should be paid to reducing drug doses and monitoring toxicity. Immunosuppressive treatment is a critical procedure in patients with chronic renal failure, in whom an increased risk of infection is already present. In conclusion, on the basis of the data of the literature, we can hypothesize that the ''point of no return'' exceeds the threshold generally considered safe by clinicians. Nevertheless, a strict definition of a cutoff value for renal function to establish whether or not a certain treatment should be given is not applicable in clinical practice, where the choice of an immunosuppressive approach must be tailored to the individual patient based on a global evaluation including renal histology, clinical conditions

  16. Successful Anti-HCV Therapy of a Former Intravenous Drug User with Sofosbuvir and Daclatasvir in a Peritranspant Setting: A Case Report

    PubMed Central

    Seifert, Leon Louis; Heinzow, Hauke; Kabar, Iyad; Christensen, Stefan; Hüsing, Anna; Schmidt, Hartmut H.-J.

    2016-01-01

    Patient: Male, 37 Final Diagnosis: Chronic HCV-infection • hepatic decompensation Symptoms: Esophageal varices • portal-hypertensive gastropathy • splenomegaly • recurrent ascitic decompensation • hepatorenal syndrome • hepatic encephalopathy Medication: — Clinical Procedure: Liver transplantation • antiviral therapy Specialty: Gastroenterology and Hepatology Objective: Unusual setting of medical care Background: Direct-acting antivirals (DAAs) represent a new hallmark in antiviral therapy of hepatitis C virus (HCV). DAAs have been shown to be safe and effective after liver transplantation (LT), but there is little information about their use in peritransplant settings. Former intravenous drug users represent an increasing group seeking HCV treatment. This case report demonstrates the successful peritransplant antiviral treatment of a former intravenous drug user who had been treated in a methadone maintenance program. Case Report: The patient was diagnosed with Child B cirrhosis for the first time in 2009. He had a Model for End-stage Liver Disease (MELD) score of 21 and started antiviral therapy with sofosbuvir (SOF) and daclatasvir (DCV) in March 2014. Due to hepatic decompensation, he received a LT in April 2014. Immunosuppression was performed with tacrolimus (TAC) and mycophenolate-mofetil (MMF), and boosted with prednisolone in the initial stage. Four weeks after his LT, the patient presented with an acute renal injury. The patient was discharged one week later after sufficient hydration, discontinuation of non-steroidal anti-phlogistics therapy, and adjustments to his immunosuppressive regimen. At the beginning of his therapy, the number of RNA copies was 13,000 IU/mL. He received 24 weeks of anti-HCV treatment with SOF and DCV; the antiviral treatment was successful and his LT was well tolerated. Conclusions: Treatment of HCV is feasible in a peritransplant setting. The antiviral regimen we used did not seem to have any relevant

  17. Treatment of simultaneous acute antibody-mediated rejection and acute cellular rejection with alemtuzumab in kidney transplantation: a case report.

    PubMed

    Jirasiritham, S; Khunprakant, R; Techawathanawanna, N; Jirasiritham, Si; Mavichak, V

    2010-04-01

    This is a case report of a living related donor kidney transplantation using basiliximab induction and maintenance immunosuppression with cyclosporine, mycophenolate sodium, and steroid. On the second posttransplant day, the patient developed acute antibody-mediated rejection, which was treated with plasmapheresis and intravenous immunoglobulin (IVIG). Five days later, the graft had still not responded to the treatment. Another biopsy revealed additional acute cellular rejection (Banff IIA). As alemtuzumab can rapidly deplete T and B lymphocytes, monocytes, and natural killer cells, the patient was treated with alemtuzumab (30 mg subcutaneously) together with methylprednisolone (500 mg) and two more plasmaphereses. The kidney graft responded within 48 hours, producing more than 4 L of urine per day. The total lymphocyte decreased from 530/microL to 50/microL remaining in the 50 to 220/microL range. The patient received valgancyclovir and cotrimoxazole as infection prophylaxis. The kidney graft responded well to the rescue treatment and the patient was discharged with a serum creatinine of 1.1 mg/mL and has been uneventfully followed in the outpatient clinic for 8 months. Today, with the potent, effective, and selective immunosuppressive regimens, the rate and severity of acute cellular rejection in kidney transplantation has decreased in most centers. However, the rate of acute antibody-mediated rejection has increased to levels greater than those of acute cellular rejection in many centers. Acute antibody-mediated rejection is more difficult and expensive to treat successfully. The treatment of acute antibody-mediated rejection included plasmapheresis and IVIG. Herein we have reported a case of kidney transplantation simultaneously developing acute antibody-mediated and acute cellular rejection; the patient was successfully treated with alemtuzumab.

  18. Impact of immunosuppressive agents on the expression of indoleamine 2,3-dioxygenase, heme oxygenase-1 and interleukin-7 in mesangial cells.

    PubMed

    Liang, Guo-Biao; Luo, Guang-Heng; Bao, Ding-Su; Chen, An-Jian; Zhuang, Yong-Xiang; Guo, Ya-Nan; Wang, Xin; Wang, Yuan-Liang; Chen, Zong-Ping; Lu, Yi-Ping; Li, You-Ping

    2015-08-01

    Chronic allograft nephropathy (CAN) is a major cause of graft loss following kidney transplantation and may result from the interactions of various immune and non-immune factors. The aim of the present study was to establish an in vitro model of glomerular mesangial cell injury in order to examine the gene expression levels of indoleamine 2,3-dioxygenase (IDO), heme oxygenase-1 (HO-1) and interleukin-7 (IL-7) in mesangial cells during the healing process as well as to investigate the effects of various immunosuppressants on the expression of these genes. The HBZY-1 glomerular mesangial cell line was pre-treated in vitro with cytochalasin B for 2 h to induce reversible damage. Following the pre-treatment, the HBZY-1 cells were divided into five groups: Blank control group, cyclosporine A (CsA) group, tacrolimus (Tac) group, mycophenolate mofetil (MMF) group and rapamycin (RAPA) group. After treating the mesangial cells with each immunosuppressive drug for 6, 12 or 24 h, the mRNA and protein expression levels of IDO, HO-1 and IL-7 were examined using reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blot and immunohistochemical analyses. The results showed that expression levels of HO-1 were significantly upregulated in response to treatment with CsA, FK506, RAPA and MMF, whereas the expression levels of IL-7 were markedly downregulated by treatment with the above immunosuppressants. CsA, FK506 and MMF significantly enhanced the expression levels of IDO, whereas RAPA exhibited no apparent effect on IDO. The present study may contribute to the understanding of the pathogenesis of CAN and provide novel strategies for the prevention and treatment of CAN.

  19. Hypogammaglobulinemia after heart transplantation: use of intravenous immunoglobulin replacement therapy in relapsing CMV disease.

    PubMed

    Sarmiento, E; Fernàndez-Yáñez, J; Muñoz, P; Palomo, J; Rodríguez-Molina, J J; Bermejo, J; Catalan, P; Bouza, E; Fernández-Cruz, E; Carbone, J

    2005-01-01

    Secondary hypogammaglobulinemia after heart transplantation may follow immunosuppressive therapy with the resultant increased risk of infections, including cytomegalovirus (CMV) disease. There is limited information on the use of intravenous immunoglobulin replacement therapy (IVIG) in heart-transplanted patients with hypogammaglobulinemia and CMV disease. We present data on five consecutive heart-transplanted patients with relapsing CMV disease, four of whom developed gastrointestinal disease. The immunosuppressive regimen included prednisone, cyclosporine A, azathioprine, mycophenolate mofetil, tacrolimus and antithymocyte globulin (ATG). Evaluation revealed CMV antigenemia. All the patients had been treated with intravenous ganciclovir. In addition, hyperimmune CMV immunoglobulin was administered in three patients. Significantly reduced levels of immunoglobulin G (IgG) were observed in the patients as compared with 15 heart-transplanted individuals without CMV disease [mean IgG levels: 323+/-18 and 639+/-63 mg/dl, respectively (p=0.003)]. IVIG [FLEBOGAMMA], 200-400 mg/kg every 21 days with the goal of maintaining normal serum IgG levels, was added for the treatment of CMV disease. Selected batches with the highest anti-CMV titers were set apart for the treatment of the patients. IVIG treatment, in combination with antiviral therapy, proved able to control CMV disease. There was a favorable clinical response and the patients became free of gastrointestinal symptoms. Detection of CMV antigens was negative after treatment. During IVIG therapy no immediate or delayed adverse effects were observed. Even if our survey was limited to five cases, the results suggest that addition of IVIG to antiviral chemotherapy might improve outcome in heart-transplanted patients with hypogammaglobulinemia and CMV disease.

  20. Role of serum interleukin-6 in deciding therapy for multidrug resistant oral lichen planus

    PubMed Central

    Marwah, Akanksha; Kaushik, Smita; Garg, Vijay K.; Gupta, Sunita

    2015-01-01

    Background Oral lichen planus (OLP) is a T cell mediated immune response. T cells locally present in the involved tissues release cytokines like interleukin-6 (IL-6), which contributes to pathogenesis of OLP. Also IL-6 has been associated with multidrug resistance protein (MRP) expression by keratinocytes. Correspondingly, upregulation of MRP was found in OLP. We conducted this study to evaluate the effects of various drugs on serum IL-6 in OLP; and correlation of these effects with the nature of clinical response and resistance pattern seen in OLP lesions with various therapeutic modalities. Thus we evaluated the role of serum IL-6 in deciding therapy for multidrug resistant OLP. Material and Methods Serum IL-6 was evaluated in 42 erosive OLP (EOLP) patients and 10 normal mucosa and 10 oral squamous cell carcinoma cases using ELISA technique. OLP patients were randomly divided into 3 groups of 14 patients each and were subjected to Pimecrolimus local application, oral Mycophenolate Mofetil (MMF) and Methotrexate (MTX) alongwith Pimecrolimus local application. IL-6 levels were evaluated before and after treatment. Results Serum IL-6 levels were raised above 3pg/ml in 26.19% erosive OLP (EOLP) cases (mean- 3.72±8.14). EOLP (5%) cases with IL-6 levels above 5pg/ml were resistant in MTX group. However significant decrease in serum IL-6 corresponding with the clinical resolution was seen in MMF group. Conclusions Significantly raised IL-6 levels in EOLP reflect the chronic inflammatory nature of the disease. As serum IL-6 levels significantly decreased in MMF group, correspondingly no resistance to treatment was noted. However with MTX there was no significant decrease in IL-6 and resistance to treatment was noted in some, especially plaque type lesions. Thus IL-6 can be a possible biomarker in deciding the best possible therapy for treatment resistant OLP. Key words:Lichen planus, biological markers, cytokines, enzyme-linked immunosorbent assay, immunosuppressive

  1. New Therapeutic Strategies for Systemic Sclerosis—a Critical Analysis of the Literature

    PubMed Central

    Zandman-Goddard, Gisele; Tweezer-Zaks, Nurit; Shoenfeld, Yehuda

    2005-01-01

    Systemic sclerosis (SSc) is a multi-system disease characterized by skin fibrosis and visceral disease. Therapy is organ and pathogenesis targeted. In this review, we describe novel strategies in the treatment of SSc. Utilizing the MEDLINE and the COCHRANE REGISTRY, we identified open trials, controlled trials, for treatment of SSc from 1999 to April 2005. We used the terms scleroderma, systemic sclerosis, Raynaud's phenomenon, pulmonary hypertension, methotrexate, cyclosporin, tacrolimus, relaxin, low-dose penicillamine, IVIg, calcium channel blockers, losartan, prazocin, iloprost, N-acetylcysteine, bosentan, cyclophosphamide, lung transplantation, ACE inhibitors, anti-thymocyte globulin, and stem cell transplantation. Anecdotal reports were omitted. Methotrexate, cyclosporin, tacrolimus, relaxin, low-dose penicillamine, and IVIg may be beneficial in improving the skin tightness in SSc. Calcium channel blockers, the angiotensin II receptor type 1 antagonist losartan, prazocin, the prostacyclin analogue iloprost, N-acetylcysteine and the dual endothelin-receptor antagonist bosentan may be beneficial for Raynaud's phenomenon. Epoprostenol and bosentan are approved for therapy of pulmonary hypertension (PAH). Other options under investigation include intravenous or aerolized iloprost. Cyclophosphamide (CYC) pulse therapy is effective in suppressing active alveolitis. Stem cell and lung transplantation is a viable option for carefully selected patients. Renal crisis can be effectively managed when hypertension is aggressively controlled with angiotensin converting enzyme (ACE) inhibitors. Patients should continue taking ACE inhibitors even after beginning dialysis in hope of discontinuing dialysis. Anti-thymocyte globulin and mycophenolate mofetil appear safe in SSc. The improvement in skin score and the apparent stability of systemic disease during the treatment period suggest that controlled studies of these agents are justified. Stem cell transplantation is under

  2. Nonsystemic vasculitic neuropathy: update on diagnosis, classification, pathogenesis, and treatment.

    PubMed

    Collins, Michael P; Periquet-Collins, Isabel

    2009-01-01

    prednisone. No randomized controlled trial of therapy has been performed in NSVN, but data from retrospective cohorts suggest that combination therapy is more effective than steroid monotherapy. Once remission has been induced, cyclophosphamide should be replaced with azathioprine or methotrexate. Refractory patients can be treated with intravenous immunoglobulin, mycophenolate, rituximab, infliximab, or alemtuzumab. Although long-term outcome is reasonably good, more than one third of patients relapse, infrequent patients die from the disease or its treatment, and still others develop chronic pain.

  3. Sewage Treatment

    NASA Technical Reports Server (NTRS)

    1976-01-01

    A million gallon-a-day sewage treatment plant in Huntington Beach, CA converts solid sewage to activated carbon which then treats incoming waste water. The plant is scaled up 100 times from a mobile unit NASA installed a year ago; another 100-fold scale-up will be required if technique is employed for widespread urban sewage treatment. This unique sewage-plant employed a serendipitous outgrowth of a need to manufacture activated carbon for rocket engine insulation. The process already exceeds new Environmental Protection Agency Standards Capital costs by 25% compared with conventional secondary treatment plants.

  4. Treatment Options

    MedlinePlus

    ... foot problems such as swelling, pain, and Raynaud's phenomenon. article Access to care: What is being done, ... lupus. article How lupus treatments can affect your child's vision Antimalarials can affect the retina, so an ...

  5. Rotavirus Treatment

    MedlinePlus

    ... Search The CDC Cancel Submit Search The CDC Rotavirus Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Rotavirus Home About Rotavirus Symptoms Transmission Prevention Treatment Photos ...

  6. Wastewater Treatment.

    ERIC Educational Resources Information Center

    Zoltek, J., Jr.; Melear, E. L.

    1978-01-01

    Presents the 1978 literature review of wastewater treatment. This review covers: (1) process application; (2) coagulation and solids separation; (3) adsorption; (4) ion exchange; (5) membrane processes; and (6) oxidation processes. A list of 123 references is also presented. (HM)

  7. Depression Treatment

    MedlinePlus

    ... 3286 After hours (404) 639-2888 Contact Media Depression Treatment Recommend on Facebook Tweet Share Compartir On ... How Do I Know if I Am Experiencing Depression? The following questions may help you determine if ...

  8. Autoimmune hepatitis: a comprehensive review.

    PubMed

    Liberal, Rodrigo; Grant, Charlotte R; Mieli-Vergani, Giorgina; Vergani, Diego

    2013-03-01

    Autoimmune hepatitis (AIH) is an immune-mediated liver disorder characterised by female preponderance, elevated transaminase and immunoglobulin G levels, seropositivity for autoantibodies and interface hepatitis. Presentation is highly variable, therefore AIH should be considered during the diagnostic workup of any increase in liver enzyme levels. Overlap/variant forms of the disease, presenting with concomitant features of primary biliary cirrhosis or primary sclerosing cholangitis are increasingly recognised. AIH is exquisitely responsive to immunosuppressive treatment, which should be instituted promptly to prevent rapid deterioration and promote remission and long-term survival. Difficult-to-treat or non-responsive patients should be treated with mycophenolate mofetil or, failing that, calcineurin inhibitors. Persistent failure to respond or lack of adherence to treatment result in end-stage liver disease. These patients, and those with fulminant liver failure (encephalopathy grade II-IV) at diagnosis, will require liver transplantation. The pathogenesis of AIH is not fully understood, although there is mounting evidence that genetic susceptibility, molecular mimicry and impaired immunoregulatory networks contribute to the initiation and perpetuation of the autoimmune attack. Liver damage is thought to be mediated primarily by CD4(pos) T-cells, although recent studies support the involvement of diverse populations, including Th17 cells. Animal models faithfully representing the human condition are needed to unravel the contribution of innate and adaptive, effector and regulatory immune responses. A deeper understanding of the pathogenesis of AIH is likely to contribute to the development of novel treatments, such as the adoptive transfer of autologous expanded antigen-specific regulatory T-cells, which ultimately aim to restore tolerance to liver-derived antigens.

  9. Sewage Treatment

    NASA Technical Reports Server (NTRS)

    1991-01-01

    Stennis Space Center's aquaculture research program has led to an attractive wastewater treatment for private homes. The system consists of a septic tank or tanks for initial sewage processing and a natural secondary treatment facility for further processing of septic tanks' effluent, consisting of a narrow trench, which contains marsh plants and rocks, providing a place for microorganisms. Plants and microorganisms absorb and digest, thus cleansing partially processed wastewater. No odors are evident and cleaned effluent may be discharged into streams or drainage canals. The system is useful in rural areas, costs about $1,900, and requires less maintenance than mechanical systems.

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

    PubMed

    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

  11. Surface Treatment

    NASA Technical Reports Server (NTRS)

    Park, Cheol (Inventor); Lowther, Sharon E. (Inventor); St.Clair, Terry L. (Inventor)

    2003-01-01

    A simple surface treatment process is provided which offers a high performance surface for a variety of applications at low cost. This novel surface treatment, which is particularly useful for Ti-6Al-4V alloys, is achieved by forming oxides on the surface with a two-step chemical process and without mechanical abrasion. First, after solvent degreasing, sulfuric acid is used to generate a fresh titanium surface. Next, an alkaline perborate solution is used to form an oxide on the surface. This acid-followed-by-base treatment is cost effective and relatively safe to use in commercial applications. In addition, it is chromium-free, and has been successfully used with a sol-gel coating to afford a strong adhesive bond that exhibits excellent durability after the bonded specimens have been subjected to a harsh 72 hour water boil immersion. Phenylethynyl containing adhesives were used to evaluate this surface treatment with a novel coupling agent containing both trialkoxysilane and phenylethynyl groups. 8 Claims, 16 Drawing Sheets

  12. Norovirus Treatment

    MedlinePlus

    ... Norovirus Infection, National Institutes of Health NoroCORE Food Virology Treatment Language: English Español (Spanish) Recommend on Facebook ... Norovirus Infection, National Institutes of Health NoroCORE Food Virology Language: English Español (Spanish) File Formats Help: How ...

  13. WATER TREATMENT

    DOEpatents

    Pitman, R.W.; Conley, W.R. Jr.

    1962-12-01

    An automated system for adding clarifying chemicals to water in a water treatment plant is described. To a sample of the floc suspension polyacrylamide or similar filter aid chemicals are added, and the sample is then put through a fast filter. The resulting filtrate has the requisite properties for monitoring in an optical turbidimeter to control the automated system. (AEC)

  14. PARACOCCIDIOIDOMYCOSIS TREATMENT

    PubMed Central

    SHIKANAI-YASUDA, Maria Aparecida

    2015-01-01

    SUMMARY Considered to be an emerging endemic mycosis in Latin America, paracoccidioidomycosis is characterized by a chronic course and involvement of multiple organs in immunocompromised hosts. Infection sequelae are mainly related to pulmonary and adrenal insufficiency. The host-parasite interaction results in different expressions of the immune response depending on parasite pathogenicity, fungal load and genetic characteristics of the host. A few controlled and case series reports have shown that azoles and fast-acting sulfa derivatives are useful treatment alternatives in milder forms of the disease. For moderate/severe cases, more prolonged treatments or even parenteral routes are required especially when there is involvement of the digestive tract mucosa, resulting in poor drug absorption. Although comparative studies have reported that shorter treatment regimens with itraconazole are able to induce cure in chronically-infected patients, there are still treatment challenges such as the need for more controlled studies involving acute cases, the search for new drugs and combinations, and the search for compounds capable of modulating the immune response in severe cases as well as the paradoxical reactions. PMID:26465367

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

    PubMed

    Heekin, Richard; Gandhy, Chetan; Robertson, Derrick

    2015-01-01

    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.

  16. Clinical Outcomes of Lung Transplantation in Patients with Telomerase Mutations

    PubMed Central

    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

  17. Updated Understanding of Autoimmune Lymphoproliferative Syndrome (ALPS).

    PubMed

    Li, Pu; Huang, Ping; Yang, Ye; Hao, Mu; Peng, Hongwei; Li, Fei

    2016-02-01

    Autoimmune lymphoproliferative syndrome (ALPS), a disorder characterized by immune dysregulation due to disrupted lymphocyte homeostasis, is mainly resulted from the mutations in FAS-mediated apoptotic pathway. In addition, other mutations of the genes such as Fas-ligand (FASLG), Caspase 10 (CASP10) and Caspase 8 (CASP8), NRAS and KRAS have also been observed in a small number of patients with ALPS or ALPS-related disorders. However, approximately 20-30% of patients with ALPS have unidentified defect. Its clinical manifestations observed in multiple family members include unexplained lymphadenopathy, hepatosplenomegaly, autoimmune cytopenias such as thrombocytopenia, neutropenia, and anemia due to excessive production of antibodies by lymphocytes, elevated number of double-negative T (DNT) cells, and increased risk of lymphoma. As a very rare disease, ALPS was first characterized in the early 1990s. More than 300 families with hereditary ALPS have been reported till now; nearly 500 patients from these families have been studied and followed worldwide over the last 20 years. ALPS has historically considered as a primary immune defect presenting in early childhood, however, recent studies have shown that it may be more common than previous thought because adult onset presentation is increasingly becoming recognized and more adult ALPS patients are diagnosed. The new genetic and biological insights have improved the understanding of ALPS and a number of targeted therapeutic strategies such as mycophenolate mofetil, sirolimus, and pentostatin have been successfully applied in ALPS patients with promising treatment efficacy. This article comprehensively reviews the clinical and laboratory manifestations, new research advances in the molecular pathogenesis, diagnosis and treatments of this disorder.

  18. Kidney transplantation in immunologically high-risk patients.

    PubMed

    Keven, K; Sengul, S; Celebi, Z K; Tuzuner, A; Yalcin, F; Duman, T; Tutkak, H

    2013-04-01

    An increased number of sensitized patients await kidney transplantation (KTx). Sensitization has a major impact on patient mortality and morbidity due to prolonged waiting time and may preclude live donor transplantation. However, recent reports have shown that KTx can be performed successfully using novel immunosuppressive protocols. This study presents our experience with patients displaying donor-specific antibody (DSA) (+). We enrolled 5 lymphocyte cross-match (LCM) negative (complement-dependent cytotoxicity) and panel-reactive antibody (PRA) plus DSA-positive patients mean fluorescein intensity [MFI] > 1000) who underwent living kidney donor procedures. All subjects were females and their mean age was 36.7 years. In our protocol, we started mycophenolate mofetil (2 g/d), tacrolimus (0.01 mg/kg) and prednisolone (0.5 mg/kg) on day -6. We performed 2 sessions of total plasma exchange (TPE) with albumin replacement and administered 2 doses of IVIG (5 g/d). On day -1, we added rituximab (200 mg). On the operation day and on day +4, the patients received doses of basiliximab. Serum samples were taken on days -6, 0, and 30 as well as at 1 year after transplantation. All patients displayed immediate graft function. Mean basal DSA titer was 5624 MFI. After desensitization, the MFI titers decreased at the time of transplantation to 2753 MFI, and were 2564 MFI at the 1st month and 802 MFI at 1st year. Three patients experienced acute rejection episodes (60%). After treatment for rejection, the average follow-up was 17 months and last creatinine levels were 0.6-0.8 mg/dL (minimum-maximum). In conclusion, KTx can be succesfully performed in sensitized patients displaying DSA. However, there seems to be a greater acute rejection risk. There is no consensus regarding adequate doses of IVIG or plasmapheresis treatments; furthermore, more studies are needed to clarify the safe MFI titer of the DSA.

  19. Resolution of C1q deposition but not of the clinical nephrotic syndrome after immunomodulating therapy in focal sclerosis

    PubMed Central

    Tibor Fülöp, Tibor; Csongrádi, Éva; Lerant, Anna A.; Lewin, Matthew; Lewin, Jack R.

    2015-01-01

    Background: The natural evolution of C1q nephropathy (C1qNP) during immunosuppressive treatment is relatively little studied or understood. Case Presentation: A 30 year-old Caucasian female was referred to us for further management of biopsy-proven C1qNP and severe nephrotic syndrome. Serologic work-up remained negative, including complement C3 and C4 levels and repeated testing for antinuclear antibodies. A renal biopsy revealed minimal change nephropathy vs. focal sclerosis on light microscopy and C1qNP on immunopathology. She has failed trials of high-dose oral prednisone, mycophenolate mofetil 1,500 mg twice a day and a subsequent regimen of monthly IV cyclophosphamide 750 mg × 9 cycles. She also received the maximum tolerated angiotensin-converting enzyme inhibitor and spironolactone therapy. Random urine protein-to-creatinine (UPC) ratio predicted proteinuria in the range between 5-35 gm/day, while serum creatinine rose progressively from 1.0 mg/dL to 1.4 mg/dL (to convert to μmol/L, multiply by 88.4). A decision was made to repeat renal biopsy to reassess the underlying histology. The biopsy revealed focal sclerosis but no C1q deposition. Conclusions: Our case illustrates at least two points: first, an established pathologic diagnosis does not obviate the need for repeated renal biopsy later on, should diagnostic uncertainty persist. Second, histological diagnoses may evolve over time, especially in a patient receiving active and powerful immune-modulating treatment. In our case, the clinical nephrosis did not change with immunosuppressive therapy while C1q deposition ceased, making this latter entity likely the immunologically mediated process. PMID:25964890

  20. Similarities and differences between pediatric and adult patients with systemic lupus erythematosus.

    PubMed

    Tarr, T; Dérfalvi, B; Győri, N; Szántó, A; Siminszky, Z; Malik, A; Szabó, A J; Szegedi, G; Zeher, M

    2015-07-01

    Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease with highest prevalence among women of childbearing age. However, children younger than 16 years also can develop SLE (childhood-onset lupus/juvenile-type SLE). The aim of our study was to compare the clinical course of adult and pediatric-onset SLE. Data from 342 adult patients followed at the University of Debrecen, Hungary, and 79 children documented in the Hungarian National Pediatric SLE registry were analyzed using hospital medical records. Organ manifestations, laboratory parameters, and immunoserological characteristics were reviewed and the results were evaluated using SPSS for Windows software.Gender distribution was not significantly different between groups with disease starting in childhood vs adulthood. The prevalence of the following manifestations was significantly higher for pediatric than for adult-onset disease including: lupus nephritis (43% pediatric vs 26.4% for adult-onset), hematological disorders (57% vs 36.4%), photosensitivity (20% vs 9%), butterfly rash (61% vs 35.5%) and mucosal ulceration (11.4% vs 4%). For adult-onset SLE, neurological symptoms (30% vs 6%) and polyarthritis (86% vs 68%) occurred significantly more frequently than in children. Anti-SSA, anti-SSB and antiphospholipid antibodies were detected at significantly higher levels in adult-onset patients compared to those in pediatrics. Children were more commonly given high-dose intravenous immunoglobulin treatment (6.3% vs 0.6%) and mycophenolate mofetil (15.2% vs 5.3%) than adults.These results suggest that pediatric and adult-onset SLE differ in multiple aspects, and it is important to recognize these differences for optimal treatment and prognosis of these patients.

  1. Efficacy and Safety of Rituximab in Moderately-to-Severely Active Systemic Lupus Erythematosus

    PubMed Central

    Merrill, Joan T.; Neuwelt, C. Michael; Wallace, Daniel J.; Shanahan, Joseph C.; Latinis, Kevin M.; Oates, James C.; Utset, Tammy O.; Gordon, Caroline; Isenberg, David A.; Hsieh, Hsin-Ju; Zhang, David; Brunetta, Paul G.

    2015-01-01

    Objective B cells are likely to contribute to the pathogenesis of systemic lupus erythematosus (SLE), and rituximab induces depletion of B cells. The Exploratory Phase II/III SLE Evaluation of Rituximab (EXPLORER) trial tested the efficacy and safety of rituximab versus placebo in patients with moderately-to-severely active extrarenal SLE. Methods Patients entered with ≥1 British Isles Lupus Assessment Group (BILAG) A score or ≥2 BILAG B scores despite background immunosuppressant therapy, which was continued during the trial. Prednisone was added and subsequently tapered. Patients were randomized at a ratio of 2:1 to receive rituximab (1,000 mg) or placebo on days 1, 15, 168, and 182. Results In the intent-to-treat analysis of 257 patients, background treatment was evenly distributed among azathioprine, mycophenolate mofetil, and methotrexate. Fifty-three percent of the patients had ≥1 BILAG A score at entry, and 57% of the patients were categorized as being steroid dependent. No differences were observed between placebo and rituximab in the primary and secondary efficacy end points, including the BILAG-defined response, in terms of both area under the curve and landmark analyses. A beneficial effect of rituximab on the primary end point was observed in the African American and Hispanic subgroups. Safety and tolerability were similar in patients receiving placebo and those receiving rituximab. Conclusion The EXPLORER trial enrolled patients with moderately-to-severely active SLE and used aggressive background treatment and sensitive cutoffs for nonresponse. No differences were noted between placebo and rituximab in the primary and secondary end points. Further evaluation of patient subsets, biomarkers, and exploratory outcome models may improve the design of future SLE clinical trials. PMID:20039413

  2. Pharmacological Management of Childhood-Onset Systemic Lupus Erythematosus.

    PubMed

    Thorbinson, Colin; Oni, Louise; Smith, Eve; Midgley, Angela; Beresford, Michael W

    2016-06-01

    Systemic lupus erythematosus (SLE) is a rare, severe, multisystem autoimmune disorder. Childhood-onset SLE (cSLE) follows a more aggressive course with greater associated morbidity and mortality than adult-onset SLE. Its aetiology is yet to be fully elucidated. It is recognised to be the archetypal systemic autoimmune disease, arising from a complex interaction between the innate and adaptive immune systems. Its complexity is reflected by the fact that there has been only one new drug licensed for use in SLE in the last 50 years. However, biologic agents that specifically target aspects of the immune system are emerging. Immunosuppression remains the cornerstone of medical management, with glucocorticoids still playing a leading role. Treatment choices are led by disease severity. Immunosuppressants, including azathioprine and methotrexate, are used in mild to moderate manifestations. Mycophenolate mofetil is widely used for lupus nephritis. Cyclophosphamide remains the first-line treatment for patients with severe organ disease. No biologic therapies have yet been approved for cSLE, although they are being used increasingly as part of routine care of patients with severe lupus nephritis or with neurological and/or haematological involvement. Drugs influencing B cell survival, including belimumab and rituximab, are currently undergoing clinical trials in cSLE. Hydroxychloroquine is indicated for disease manifestations of all severities and can be used as monotherapy in mild disease. However, the management of cSLE is hampered by the lack of a robust evidence base. To date, it has been principally guided by best-practice guidelines, retrospective case series and adapted adult protocols. In this pharmacological review, we provide an overview of current practice for the management of cSLE, together with recent advances in new therapies, including biologic agents.

  3. A Comparison of Two Types of Rabbit Antithymocyte Globulin Induction Therapy in Immunological High-Risk Kidney Recipients: A Prospective Randomized Control Study

    PubMed Central

    Burkhalter, F.; Schaub, S.; Bucher, Ch.; Gürke, L.; Bachmann, A.; Hopfer, H.; Dickenmann, M.; Steiger, J.; Binet, I.

    2016-01-01

    Background Induction treatment with rabbit polyclonal antithymocyte globulins (ATGs) is frequent used in kidney transplant recipients with donorspecific HLA antibodies and shows acceptable outcomes. The two commonly used ATGs, Thymoglobulin and ATG-F have slightly different antigen profile and antibody concentrations. The two compounds have never been directly compared in a prospective trial in immunological high-risk recipients. Therefore we performed a prospective randomized controlled study comparing the two compounds in immunological high-risk kidney recipients in terms of safety and efficacy. Methods Immunological high-risk kidney recipients, defined as the presence of HLA DSA but negative CDC-B and T-cell crossmatches were randomized 1:1 to receive ATG-F or Thymoglobulin. Maintenance immunosuppressive therapy consisted of tacrolimus, mycophenolate mofetil and steroids. Results The per-protocol analysis included 35 patients. There was no immediate infusion reaction observed with both compounds. No PTLD or malignancy occurred during the follow-up in both groups. The incidence of viral and bacterial infections was similar in both groups (p = 0.62). The cumulative incidence of clinical and subclinical antibody mediated allograft rejection as well as T-cell mediated allograft rejection during the first year between ATG-F and Thymoglobulin was similar (35% versus 19%; p = 0.30 and 11% versus 18%; 0.54 respectively). The two-year graft function was similar with a median eGFR of 56 ml/min/1.73m2 (range 21–128) (ATG-F-group) and 51 ml/min/1.73m2 (range 22–132) (Thymo-group) (p = 0.69). Conclusion We found no significant differences between the compared study drugs for induction treatment in immunological high-risk patients regarding safety and efficacy during follow-up with good allograft function at 2 years after transplantation. PMID:27855166

  4. Nephrotic syndrome and idiopathic membranous nephropathy associated with autosomal-dominant polycystic kidney disease.

    PubMed

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

    2011-05-05

    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.

  5. Myelodysplastic/ Myeloproliferative Neoplasms Treatment

    MedlinePlus

    ... Myeloproliferative Neoplasms Treatment Myelodysplastic/ Myeloproliferative Neoplasms Treatment Myelodysplastic/ Myeloproliferative Neoplasms Treatment (PDQ®)–Patient Version General Information About Myelodysplastic/ ...

  6. Chronic Myeloproliferative Neoplasms Treatment

    MedlinePlus

    ... Myeloproliferative Neoplasms Treatment Myelodysplastic/ Myeloproliferative Neoplasms Treatment Chronic Myeloproliferative Neoplasms Treatment (PDQ®)–Patient Version General Information About Chronic ...

  7. A simplified immune suppression scheme leads to persistent micro-dystrophin expression in Duchenne muscular dystrophy dogs.

    PubMed

    Shin, Jin-Hong; Yue, Yongping; Srivastava, Arun; Smith, Bruce; Lai, Yi; Duan, Dongsheng

    2012-02-01

    Highly abbreviated micro-dystrophin genes have been intensively studied for Duchenne muscular dystrophy (DMD) gene therapy. Following adeno-associated virus (AAV) gene transfer, robust microgene expression is achieved in murine DMD models in the absence of immune suppression. Interestingly, a recent study suggests that AAV gene transfer in dystrophic dogs may require up to 18 weeks' immune suppression using a combination of three different immune-suppressive drugs (cyclosporine, mycophenolate mofetil, and anti-dog thymocyte globulin). Continued immune suppression is not only costly but also may cause untoward reactions. Further, some of the drugs (such as anti-dog thymocyte globulin) are not readily available. To overcome these limitations, we developed a novel 5-week immune suppression scheme using only cyclosporine and mycophenolate mofetil. AAV vectors (either AV.RSV.AP that expresses the heat-resistant human alkaline phosphatase gene, or AV.CMV.μDys that expresses the canine R16-17/H3/ΔC microgene) at 2.85×10(12) vg particles were injected into adult dystrophic dog limb muscles under the new immune suppression protocol. Sustained transduction was observed for nearly half year (the end of the study). The simplified immune suppression strategy described here may facilitate preclinical studies in the dog model.

  8. Strategic breakthrough in adult ABO-incompatible living donor liver transplantation: preliminary results of consecutive seven cases.

    PubMed

    Soejima, Yuji; Muto, Jyun; Matono, Rumi; Ninomiya, Mizuki; Ikeda, Tetsuo; Yoshizumi, Tomoharu; Uchiyama, Hideaki; Ikegami, Toru; Shirabe, Ken; Maehara, Yoshihiko

    2013-01-01

    ABO-incompatibility is a major obstacle to expanding exiguous donor pools in adult liver transplantation, especially in countries where grafts from deceased donors are uncommon. We present our preliminary results of ABO-incompatible (ABO-I) adult living donor liver transplantation (LDLT) using a new, simple protocol. Seven consecutive cases of ABO-I LDLT were managed by the same protocol including pre-operative administration of a single dose of rituximab (375 mg/m(2) ) followed by three to five sessions of plasma exchange before LDLT without portal infusion therapy. The triple immunosuppression protocol consisted of tacrolimus, mycophenolate mofetil and steroids, with mycophenolate mofetil starting seven d before LDLT. Splenectomy was performed for all cases. All patients are alive (100% survival) with a mean follow-up of 852 d (715-990 d). Neither antibody-mediated nor hyperacute rejection were encountered. There was only one episode of mild acute cellular rejection, for which steroid augmentation was effective. The median preformed isoagglutinin antibody titer before plasma exchange was 256, while the median antibody titer immediately before LDLT was 16. In conclusion, adult ABO-I LDLT results were excellent - comparable or even superior to those of ABO-compatible LDLT. ABO-I adult LDLT has now become a more applicable modality without the need for an appropriate donor.

  9. A scoping review of the use of non-biologic disease modifying anti-rheumatic drugs in the management of large vessel vasculitis.

    PubMed

    Misra, Durga Prasanna; Sharma, Aman; Kadhiravan, Tamilarasu; Negi, Vir Singh

    2017-02-01

    Takayasu's arteritis (TA) and Giant cell arteritis (GCA) comprise the large vessel vasculitides (LVV). Patients with LVV are treated with disease-modifying anti-rheumatic drugs (DMARDs), both conventional (cDMARDs) and biologic (bDMARDs). We undertook a scoping review to assess the effectiveness of cDMARDs in TA and GCA. We could identify 11 studies in TA and 18 studies in GCA. There were only 3 randomized controlled trials on methotrexate, one on hydroxychloroquine and two on cyclosporine in GCA, the others being case series (including all studies on TA). Most of these studies had small patient numbers (median 15 in TA and 27 in GCA). Outcome measures reported in different studies were heterogenous. Overall, methotrexate, leflunomide, azathioprine, mycophenolate mofetil and cyclophosphamide were effective in TA (low quality of evidence). Methotrexate (high quality of evidence), hydroxychloroquine and cyclosporine (moderate quality of evidence) appeared to be ineffective in GCA. Azathioprine (moderate quality of evidence), leflunomide, mycophenolate mofetil, cyclophosphamide and dapsone (low quality of evidence) were effective in GCA. There exists a paucity of high quality evidence to guide use of cDMARDs in TA and GCA. There is an unmet need to conduct large multi-centric randomized placebo-controlled trials to accurately assess the utility on cDMARDs in LVV.

  10. A Simplified Immune Suppression Scheme Leads to Persistent Micro-dystrophin Expression in Duchenne Muscular Dystrophy Dogs

    PubMed Central

    Shin, Jin-Hong; Yue, Yongping; Srivastava, Arun; Smith, Bruce; Lai, Yi

    2012-01-01

    Abstract Highly abbreviated micro-dystrophin genes have been intensively studied for Duchenne muscular dystrophy (DMD) gene therapy. Following adeno-associated virus (AAV) gene transfer, robust microgene expression is achieved in murine DMD models in the absence of immune suppression. Interestingly, a recent study suggests that AAV gene transfer in dystrophic dogs may require up to 18 weeks' immune suppression using a combination of three different immune-suppressive drugs (cyclosporine, mycophenolate mofetil, and anti-dog thymocyte globulin). Continued immune suppression is not only costly but also may cause untoward reactions. Further, some of the drugs (such as anti-dog thymocyte globulin) are not readily available. To overcome these limitations, we developed a novel 5-week immune suppression scheme using only cyclosporine and mycophenolate mofetil. AAV vectors (either AV.RSV.AP that expresses the heat-resistant human alkaline phosphatase gene, or AV.CMV.μDys that expresses the canine R16-17/H3/ΔC microgene) at 2.85×1012 vg particles were injected into adult dystrophic dog limb muscles under the new immune suppression protocol. Sustained transduction was observed for nearly half year (the end of the study). The simplified immune suppression strategy described here may facilitate preclinical studies in the dog model. PMID:21967249

  11. Alemtuzumab Induction and Delayed Acute Rejection in Steroid-Free Simultaneous Pancreas-Kidney Transplant Recipients

    PubMed Central

    Bank, Jonna R.; Heidt, Sebastiaan; Moes, Dirk Jan A. R.; Roelen, Dave L.; Mallat, Marko J. K.; van der Boog, Paul J.M.; Vergunst, Manon; Jol-van der Zijde, Cornelia M.; Bredius, Robbert G. M.; Braat, Andries E.; Ringers, Jan; van Tol, Maarten J. D.; Claas, Frans H. J.; Reinders, Marlies E. J.; de Fijter, Johannes W.

    2017-01-01

    Background The optimal immunosuppressive regimen in simultaneous pancreas-kidney transplant (SPKT) recipients that prevents acute rejection episodes (AREs) and allows optimal outcome remains elusive. Methods This cohort study assessed incidence and time to AREs in 73 consecutive SPKT recipients receiving alemtuzumab induction and steroid-free maintenance with tacrolimus and mycophenolate mofetil. A cohort with single high-dose antithymocyte globulin (ATG; n = 85) and triple therapy served as controls. In addition, we provided mechanistic insights in AREs after alemtuzumab depletion, including composition and alloreactivity of lymphocytes (flow cytometry and mixed lymphocyte reaction) plasma alemtuzumab levels (enzyme-linked immunosorbent assay), and maintenance drug exposure. Results Overall number of AREs at 3 years was significantly lower with alemtuzumab versus ATG induction (26.0% vs 43.5%; adjusted hazard ratio, 0.38; P = 0.029). Most AREs (94.6%) with ATG occurred within the first month, whereas 84.2% of AREs with alemtuzumab occurred beyond 3 months. Patients with and without an ARE in the steroid-free alemtuzumab group showed no differences in composition of lymphocytes, or in alemtuzumab levels. Of note, more than two thirds of these AREs were preceded by empiric tacrolimus and/or mycophenolate mofetil dose adjustments due to viral infections, leukopenia, or gastrointestinal symptoms. Conclusions Alemtuzumab induction resulted in a significant lower incidence of AREs. Empiric dose adjustments beyond 3 months in the absence of steroids carry a significant risk for subsequent rejection in SPKT recipients. PMID:28349124

  12. Antimicrobials Treatment

    NASA Astrophysics Data System (ADS)

    Drosinos, Eleftherios H.; Skandamis, Panagiotis N.; Mataragas, Marios

    The use of antimicrobials is a common practice for preservation of foods. Incorporation, in a food recipe, of chemical antimicrobials towards inhibition of spoilage and pathogenic micro-organisms results in the compositional modification of food. This treatment is nowadays undesirable for the consumer, who likes natural products. Scientific community reflecting consumers demand for natural antimicrobials has made efforts to investigate the possibility to use natural antimicrobials such us bacteriocins and essential oils of plant origin to inhibit microbial growth.

  13. Active and Repressive Chromatin-Associated Proteome after MPA Treatment and the Role of Midkine in Epithelial Monolayer Permeability

    PubMed Central

    Khan, Niamat; Lenz, Christof; Binder, Lutz; Pantakani, Dasaradha Venkata Krishna; Asif, Abdul R.

    2016-01-01

    Mycophenolic acid (MPA) is prescribed to maintain allografts in organ-transplanted patients. However, gastrointestinal (GI) complications, particularly diarrhea, are frequently observed as a side effect following MPA therapy. We recently reported that MPA altered the tight junction (TJ)-mediated barrier function in a Caco-2 cell monolayer model system. This study investigates whether MPA induces epigenetic changes which lead to GI complications, especially diarrhea. Methods: We employed a Chromatin Immunoprecipitation-O-Proteomics (ChIP-O-Proteomics) approach to identify proteins associated with active (H3K4me3) as well as repressive (H3K27me3) chromatin histone modifications in MPA-treated cells, and further characterized the role of midkine, a H3K4me3-associated protein, in the context of epithelial monolayer permeability. Results: We identified a total of 333 and 306 proteins associated with active and repressive histone modification marks, respectively. Among them, 241 proteins were common both in active and repressive chromatin, 92 proteins were associated exclusively with the active histone modification mark, while 65 proteins remained specific to repressive chromatin. Our results show that 45 proteins which bind to the active and seven proteins which bind to the repressive chromatin region exhibited significantly altered abundance in MPA-treated cells as compared to DMSO control cells. A number of novel proteins whose function is not known in bowel barrier regulation were among the identified proteins, including midkine. Our functional integrity assays on the Caco-2 cell monolayer showed that the inhibition of midkine expression prior to MPA treatment could completely block the MPA-mediated increase in barrier permeability. Conclusions: The ChIP-O-Proteomics approach delivered a number of novel proteins with potential implications in MPA toxicity. Consequently, it can be proposed that midkine inhibition could be a potent therapeutic approach to prevent the

  14. Sewage Treatment

    NASA Technical Reports Server (NTRS)

    1984-01-01

    In the early 1970's, National Space Technology Laboratories discovered that water hyacinths literally thrive on sewage; they absorb and digest nutrients and minerals from wastewater, converting sewage effluents to clean water. They offer a means of purifying water at a fraction of the cost of a conventional sewage treatment plant, and provide a bonus value in byproducts. Hyacinths must be harvested at intervals; the harvested plants are used as fertilizers, high-protein animal feed and a source of energy. Already serving a number of small towns, the "aquaculture" technique has significantly advanced with its adoption by a major U.S. city.

  15. [Osteoporosis treatment].

    PubMed

    Uebelhart, B; Rizzoli, R

    2006-01-04

    As for any chronic disease, adherence to osteoporosis treatment is low. Folates and vitamin B12 decrease hip fracture risk in elderly Japanese with stroke. Raloxifene (Evista) decreases the incidence of positive estrogen receptor breast cancer and could prevent cardiovascular events in patients at high risk. Strontium ranelate (Protélos) prevents hip fracture in elderly women. The action of alendronate (Fosamax) on bone mineral density and markers of bone remodelling is of higher amplitude than that of risedronate (Actonel). Once monthly ibandronate (Bonviva) increases bone mineral density in post menopausal women with osteoporosis. Excessive suppression of bone remodelling and osteonecrosis of the yaws could be related to bisphosphonate intake.

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

    SciTech Connect

    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.

  17. 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?

    PubMed

    Synesiou, Elena; Fairbanks, Lynnette D; Simmonds, H Anne; Slominska, Ewa M; Smolenski, Ryszard T; Carrey, Elizabeth A

    2011-06-01

    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, N(1)-methylnicotinamide and 4Py-riboside) and the major nicotinamide metabolite N(1)-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.

  18. Systemic Immunosuppression in High-Risk Penetrating Keratoplasty: A Systematic Review

    PubMed Central

    Bali, Shveta; Filek, Richard; Si, Francie; Hodge, William

    2016-01-01

    Cornea transplantation has a high success rate and typically only requires topical immunomodulation. However, in high-risk cases, systemic immunosuppression can be used. We conducted a systematic review on the efficacy and side effects of systemic immunosuppression for high-risk cornea transplantation. The study population was 18 years old or older with a high-risk transplant (two or more clock hours of cornea vascularization or a previous failed graft or a graft needed because of herpes simplex keratitis). A comprehensive search strategy was performed with the help of an information specialist and content experts from ophthalmology. All study designs were accepted for assessment. Level 1 and level 2 screening was performed by two reviewers followed by data abstraction. Forest plots were created whenever possible to synthesize treatment effects. Quality assessment was done with a Downs and Blacks score. From 1,150 articles, 29 were ultimately used for data abstraction. The odds ratios (ORs) for clear graft survival in cyclosporine and controls were 2.43 (95% CI: 1.00 - 5.88) and 3.64 (95% CI: 1.48 - 8.91) for rejection free episodes. Mycophenolate mofetil (MMF) significantly improved the rejection free graft survival rates at 1 year (OR: 4.05, 95% CI: 1.83 - 8.96). The overall results suggested that both systemic cyclosporine and MMF improved 1-year rejection free graft survival in high-risk keratoplasty. Cyclosporine also significantly improved clear graft survival rates at 1 year; however, there were insufficient data to analyze the same in the MMF group. Higher quality studies are needed to understand this issue better. PMID:26985246

  19. Efficacy and safety of concentration-controlled everolimus with reduced-dose cyclosporine in Japanese de novo renal transplant patients: 12-month results

    PubMed Central

    2013-01-01

    Background No study to date has evaluated the efficacy and safety of everolimus with reduced-exposure cyclosporine in Japanese de-novo renal transplant (RTx) patients. Methods This 12-month, multicenter, open-label study randomized (1:1) 122 Japanese de-novo RTx patients to either an everolimus regimen (1.5 mg/day starting dose (target trough: 3 to 8 ng/ml) + reduced-dose cyclosporine) or a mycophenolate mofetil (MMF) regimen (2 g/day + standard dose cyclosporine). All patients received basiliximab and corticosteroids. Key endpoints at month 12 were composite efficacy failure (treated biopsy-proven acute rejection, graft loss, death, or loss to follow-up) and renal function (estimated glomerular filtration rate; Modification of Diet in Renal Disease-4). Results Clear cyclosporine exposure reduction was achieved in the everolimus group throughout the study (52% reduction at month 12). Month 12 efficacy failure rates showed everolimus 1.5 mg to be non-inferior to MMF (11.5% vs. 11.5%). The median estimated glomerular filtration rate at month 12 was 58.00 ml/minute/1.73 m2 in the everolimus group versus 55.25 ml/minute/1.73 m2 in the MMF group (P = 0.063). Overall, the incidence of adverse events was comparable between the groups with some differences in line with the known safety profile of the treatments. The everolimus group had a higher incidence of wound healing events and edema, whereas a higher rate of cytomegalovirus infections was reported in the MMF group. Conclusions This study confirmed the efficacy of everolimus 1.5 mg/day (target trough: 3 to 8 ng/ml) in Japanese RTx patients for preventing acute rejection, while allowing for substantial cyclosporine sparing. Renal function and safety findings were comparable with previous reports from other RTx populations. Trial registration ClinicalTrials.gov number: NCT00658320 PMID:23866828

  20. Significant infections after hand transplantation in a Polish population.

    PubMed

    Kamińska, D; Kościelska-Kasprzak, K; Myszka, M; Banasik, M; Chełmoński, A; Boratyńska, M; Jabłecki, J; Klinger, M

    2014-10-01

    The study was conducted to assess serious infectious complications in five hand allograft recipients (four males, one female, age 40 ± 10 years), transplanted between 2006 and 2010. All donors and recipients were positive but one for cytomegalovirus (CMV) immunoglobulin G. All recipients received immunosuppressive therapy basiliximab, tacrolimus, mycophenolate mofetil and methylprednisolone. Until May 2013, there were four cases of severe infections requiring hospitalization. One patient developed CMV infection on the 28th postoperative day. Despite therapy with ganciclovir and prophylaxis with valganciclovir, reinfection episodes occurred both 4 weeks and 7 months later. The female recipient developed CMV infection 8 months after hand transplantation. After 3 weeks of ganciclovir treatment, the polymerase chain reaction results remained negative. We found that the CD4/CD8 T lymphocytes ratio differs in those two patients who had developed CMV disease in the past in comparison to the three remaining hand transplant recipients (mean 0.46 versus 1.7, respectively). Moreover, the ratio of patients who were CD4-8 negative to total T lymphocytes in CMV recovered patients was two-fold higher compared to the remaining recipients (10.0 versus 4.4, respectively). The female recipient was also hospitalized because of acute tonsillitis 25 months after hand transplantation, and successfully treated with amoxicillin clavulanate. The third recipient was hospitalized because of severe acute pain involving right lower limb, especially foot, 74 months after hand transplantation. After 48 hours, a painful vesicular rash occurred on the plantar as well as dorsal surface of right foot and herpes zoster was diagnosed. Immunosuppressive therapy after hand transplantation may be complicated by serious infections. CMV disease was associated with persistent alterations in T lymphocyte subsets.

  1. Lupus Erythematosus and Neutrophilic Urticarial Dermatosis

    PubMed Central

    Gusdorf, Laurence; Bessis, Didier; Lipsker, Dan

    2014-01-01

    Abstract Neutrophilic urticarial dermatosis (NUD) resembles urticaria clinically but is a neutrophilic dermatosis histopathologically. The majority of patients with NUD have an underlying systemic condition, mainly, autoinflammatory disorders such as cryopyrin-associated periodic syndromes, Schnitzler syndrome, and adult-onset Still disease, but a few also have systemic lupus erythematosus (LE). Here, we confirm these data and we report relevant clinical and histopathological data of 7 patients with LE and NUD. We retrospectively retrieved the medical records of all patients with LE in whom skin biopsy showed NUD in registers of Strasbourg and Montpellier University hospitals since 2000. All were female and aged between 13 and 45 years. Skin lesions were typically rose or red macules or slightly elevated papules occurring in a wide distribution. Individual lesions resolved within 24 hours and were not or only slightly itchy. Every patient had associated signs, most of the time polyarthritis and/or fever. NUD was the presenting mode of LE in 2 patients. NUD was misdiagnosed as a classic lupus flare and led to therapeutic intensification with the introduction of immunosuppressive drugs in 4 patients. Histopathological findings consisted of intense neutrophilic interstitial and perivascular infiltrate with leukocytoclasia and without fibrinoid necrosis of vessel walls. Direct immunofluorescence testing showed a lupus band in 4 patients. Antinuclear antibodies were always positive, anti-dsDNA antibodies were positive in 5 patients, and anti-Ro/SSA antibodies in 6 patients. Immunosuppressive drugs such as prednisone, hydroxychloroquine, mycophenolate mofetil, and methotrexate were never effective to treat NUD. Antihistamines were effective in 1 patient and dapsone or colchicine was effective in 5 patients. NUD is not exceptional in patients with systemic LE and is easily misdiagnosed as an acute LE flare. Furthermore, we show that conventional immunosuppressive LE

  2. Hematopoietic Stem Cell Transplantation for Homozygous β Thalassemia and β Thalassemia/Hemoglobin E Patients from Haploidentical Donors

    PubMed Central

    Anurathapan, U; Hongeng, S; Pakakasama, S; Sirachainan, N; Songdej, D; Chuansumrit, A; Charoenkwan, P; Jetsrisuparb, A; Sanpakit, K; Rujkijyanont, P; Meekaewkunchorn, A; Lektrakul, Y; Iamsirirak, P; Surapolchai, P; Satayasai, W; Sirireung, S; Sruamsiri, R; Wahidiyat, PA; Ungkanont, A; Issaragrisil, S; Andersson, BS

    2016-01-01

    Thalassemia free survival after allogeneic stem cell transplantation (SCT) is about 80–90% with either matched related or unrelated donors. However, the probability of finding a HLA-compatible donor is less than 50%. We explored the use of a mismatched related (“Haplo-”) donor. All patients received two courses of pre-transplant immunosuppression therapy (PTIS) with fludarabine (Flu) and dexamethasone (Dxm) to facilitate engraftment. After two courses of PTIS, a reduced-toxicity conditioning regimen of rabbit anti-thymocyte globulin (ATG), Flu, and IV Busulfan (Bu) was given followed by T-cell replete peripheral blood progenitor cells (PBPC). GVHD prophylaxis consisted of cyclophosphamide (Cy) on days SCT +3 and +4 (Post-Cy), and on day SCT +5 tacrolimus or sirolimus was started together with a short course of mycophenolate mofetil. Thirty-one patients underwent haplo-SCT. Their median age was ten years (range, 2 to 20 years). Twenty-nine patients engrafted with 100% donor chimerism. Two of three patients with high titers of donor-specific anti-HLA antibodies suffered primary graft failure. Median time to neutrophil engraftment was 14 days (range, 11 to 18 days). Five patients developed mild to moderate, reversible veno-occlusive disease, while nine patients developed acute GVHD grade II, that quickly responded to steroid therapy. Only five patients developed limited chronic GVHD. Projected overall and event-free survival rates at two years are 95% and 94%, respectively. The median follow up time is 12 months (range; 7 to 33 months). This haplo-SCT protocol may yield excellent outcomes for thalassemia patients, and provide a treatment option for patients lacking a HLA-matched donor. PMID:26878659

  3. The overlap syndromes of autoimmune hepatitis.

    PubMed

    Czaja, Albert J

    2013-02-01

    Autoimmune hepatitis has two major variant phenotypes in which the features of classical disease are co-mingled with those of primary biliary cirrhosis or primary sclerosing cholangitis. These overlap syndromes lack codified diagnostic criteria, established pathogenic mechanisms, and confident management strategies. Their clinical importance relates mainly to the identification of patients who respond poorly to conventional corticosteroid treatment. Scoring systems that lack discriminative power have been used in their definition, and a clinical phenotype based on pre-defined laboratory and histological findings has not been promulgated. The frequency of overlap with primary biliary cirrhosis is 7-13 %, and the frequency of overlap with primary sclerosing cholangitis is 8-17 %. Patients with autoimmune hepatitis and features of cholestatic disease must be distinguished from patients with cholestatic disease and features of autoimmune hepatitis. Variants of the overlap syndromes include patients with small duct primary sclerosing cholangitis, antimitochondrial antibody-negative primary biliary cirrhosis, autoimmune sclerosing cholangitis, and immunoglobulin G4-associated disease. Conventional corticosteroid therapy alone or in conjunction with ursodeoxycholic acid (13-15 mg/kg daily) has been variably effective, and cyclosporine, mycophenolate mofetil, and budesonide have been beneficial in selected patients. The key cholestatic features that influence the prognosis of autoimmune hepatitis must be defined and incorporated into the definition of the syndrome rather than rely on designations that imply the co-mingling of different diseases with manifestations of variable clinical relevance. The overlap syndromes in autoimmune hepatitis are imprecise, heterogeneous, and unfounded, but they constitute a clinical reality that must be accepted, diagnosed, refined, treated, and studied.

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

    PubMed Central

    Bang, So-Young; Lee, Chang Keun; Kang, Young Mo; Kim, Hyoun-Ah; Suh, Chang-Hee; Chung, Won Tae; Park, Yong-Beom; Choe, Jung-Yoon; Kim, Tae-Jong; Park, Yong-Wook; Yoo, Dae-Hyun; Bae, Sang-Cheol; Lee, Hye-Soon

    2012-01-01

    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. PMID:23304457

  5. FTY720 versus MMF with cyclosporine in de novo renal transplantation: a 1-year, randomized controlled trial in Europe and Australasia.

    PubMed

    Salvadori, M; Budde, K; Charpentier, B; Klempnauer, J; Nashan, B; Pallardo, L M; Eris, J; Schena, F P; Eisenberger, U; Rostaing, L; Hmissi, A; Aradhye, S

    2006-12-01

    FTY720 is a novel immunomodulator investigated in de novo renal transplantation and other therapeutic areas including multiple sclerosis. This 1-year multicenter, randomized, phase III study in 668 de novo renal transplant patients compared FTY720 2.5 mg plus full-dose cyclosporine (FDC) or FTY720 5.0 mg plus reduced-dose cyclosporine (RDC), with mycophenolate mofetil (MMF) plus FDC. The primary efficacy endpoint was the composite incidence of first treated biopsy-proven acute rejection (BPAR), graft loss, death or premature study discontinuation at month 12. Primary efficacy with FTY720 2.5 mg and MMF (32.4% and 30.2%; p = NS), plus mortality and BPAR incidence, were comparable. Patients receiving FTY720 5.0 mg plus RDC were discontinued from treatment due to increased risk of acute rejection (primary endpoint incidence 47.3%). FTY720 was associated with lower creatinine clearance (month 12: 53.1, 56.0 vs. 65.1 mL/min; p < 0.001) and more macular edema cases (2.2% and 1.3% vs. 0%), whereas cytomegalovirus infections were higher with MMF (6.2% and 10.6% vs. 18.1% p < 0.0001 and p = 0.0139, respectively). FTY720 2.5 mg provided comparable rejection prophylaxis over 12 months versus MMF; however, FTY720 5.0 mg did not support a 50% reduction in cyclosporine exposure. The cause of macular edema cases and lower creatinine clearance with FTY720 in de novo transplantation needs further investigation.

  6. Asymptomatic Pulmonary Allograft Kaposi Sarcoma: A Case Report.

    PubMed

    Nannini, Nazarena; Rebusso, Alessandro; Lunardi, Francesca; Loy, Monica; Calabrese, Francesca; Battistella, Lucia; Schiavon, Marco; Rea, Federico; Calabrese, Fiorella

    2016-01-14

    Solid-organ transplant recipients are at high risk of developing malignancies. A greater risk of Kaposi sarcoma has been reported in lung recipients in our country, particularly in those from Southern Italy, probably due to the high prevalence of Human herpes virus 8 infection. Kaposi sarcoma affecting only the lung allograft is extremely rare. We describe a case of a lung recipient who developed Kaposi sarcoma only in the graft, 22 months after transplant. The patient, a 65-year-old man from Southern Italy, underwent bilateral lung transplant for idiopathic pulmonary fibrosis in January 2009. He developed mild/moderate acute cellular rejection (≥A2) in 4 of 6 scheduled transbronchial biopsies thus was treated with increased immunosuppressive therapy, shifting from cyclosporine to tacrolimus and mycophenolate mofetil. In July 2010, a high-resolution computed tomography scan showed small bilateral lung nodules, despite a generally good condition. After 2 months, his condition worsened with a severe weight loss. A positron emission tomography scan showed mild metabolic activity in the lesions with no other localizations. In October 2010, a lung biopsy was performed, with results showing typical histologic and immunohistochemical features of Kaposi sarcoma. Molecular tissue evaluations and serologic analyses were positive for Human herpes virus 8. The patient's immunosuppressive therapy was suspended, and he started liposomal doxorubicin treatment; however, after the first cycle, he developed severe respiratory dysfunction. The patient died 27 months after lung transplant for neoplasm. Our report highlights the importance of considering Kaposi sarcoma in the differential diagnosis for lung nodules in lung transplant recipients, even in the absence of any initial specific symptom or cutaneous lesion.

  7. Collapsing glomerulopathy in systemic lupus erythematosus.

    PubMed

    Abadeer, Kerolos; Alsaad, Ali A; Geiger, Xochiquetzal J; Porter, Ivan E

    2017-02-27

    Collapsing glomerulopathy (CG) is a rare disease that can be associated with multiple other disorders. It usually leads to poor prognosis with a high percentage of patients progressing to end-stage renal disease. In this article, we illustrate a clinical case of CG associated with systemic lupus erythematosus that had a prompt response to mycophenolate and prednisone. The condition started after sudden cessation of the already established mycophenolate treatment regimen. The patient then presented with acute kidney injury due to kidney biopsy-proven CG. In that circumstance, we hypothesised that mycophenolate may play a role in prevention and development of CG.

  8. Treatment for HIV

    MedlinePlus

    ... and Public Home » Treatment » Treatment Decisions and HIV HIV/AIDS Menu Menu HIV/AIDS HIV/AIDS Home ... here Enter ZIP code here Treatment Decisions and HIV for Veterans and the Public Treatment for HIV: ...

  9. Paediatric Autoimmune Liver Disease.

    PubMed

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

    2015-01-01

    In paediatrics, there are 2 liver disorders in which liver damage most likely stems from an autoimmune attack: 'classical' autoimmune hepatitis (AIH) and the AIH/sclerosing cholangitis overlap syndrome (also known as autoimmune sclerosing cholangitis, ASC). The presentation of childhood autoimmune liver disease (AILD) is non-specific and can mimic most other liver disorders. AIH is exquisitely responsive to immunosuppressive treatment, which should be instituted promptly to prevent rapid deterioration and promote remission and long-term survival. Difficult-to-treat or non-responsive patients should be treated with mycophenolate mofetil; if this fails then calcineurin inhibitors can be tried. Persistent failure to respond or lack of adherence to treatment result in end-stage liver disease. These patients, and those with fulminant liver failure at diagnosis, will require liver transplantation. ASC responds to the same immunosuppressive treatment used for AIH when treatment is initiated early. Abnormal liver function tests often resolve within a few months of treatment, although medium- to long-term prognosis is worse than that of AIH because bile duct disease continues to progress despite treatment in approximately 50% of patients. Ursodeoxycholic acid is usually added to conventional treatment regimen in ASC, but whether this actually helps arrest the progression of bile duct disease remains to be established. The pathogenesis of paediatric-onset AILD is not fully understood, although there is mounting evidence that genetic susceptibility, molecular mimicry and impaired immunoregulatory networks contribute to the initiation and perpetuation of the autoimmune attack. Liver damage is thought to be mediated primarily by CD4pos T-cells. While Th1 effector cells are associated with hepatocyte damage in both AIH and ASC, Th17 immune responses predominate in the latter where they correlate with biochemical indices of cholestasis, indicating that IL-17 is involved in the

  10. Dengue Fever Treatment

    MedlinePlus

    ... linkedin Dengue Fever Treatment Dengue Fever Dengue Fever Biology and Transmission Prevention Diagnosis Treatment Featured Research NIAID- ... last reviewed on February 8, 2011 Dengue Fever Biology and Transmission Prevention Diagnosis Treatment Featured Research ^ Return ...

  11. Body Lice Treatment

    MedlinePlus

    ... Treatment FAQs Malathion FAQs Epidemiology & Risk Factors Disease Biology Diagnosis Treatment Prevention & Control Resources for Health Professionals ... Frequently Asked Questions (FAQs) Epidemiology & Risk Factors Disease Biology Diagnosis Treatment Prevention & Control Resources for Health Professionals ...

  12. Hepatitis C: Treatment

    MedlinePlus

    ... Public Home » Hepatitis C » Hepatitis C Treatment Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... Enter ZIP code here Enter ZIP code here Hepatitis C Treatment for Veterans and the Public Treatment ...

  13. Childhood Ependymoma Treatment

    MedlinePlus

    ... before the cancer is diagnosed and continue for months or years. Childhood brain and spinal cord tumors ... after treatment. Some cancer treatments cause side effects months or years after treatment has ended. These are ...

  14. Childhood Astrocytomas Treatment

    MedlinePlus

    ... before the cancer is diagnosed and continue for months or years. Signs or symptoms caused by the ... after treatment. Some cancer treatments cause side effects months or years after treatment has ended. Side effects ...

  15. Industrial Water Treatment Primer

    DTIC Science & Technology

    1992-03-01

    29 C. TREATMENT PROGRAMS ........................ 30 1. Nitrite- Borax Treatment Program ..... 30 2. Molybdate-Caustic Soda Treatment...CHILLED WATER .... SYSTEMS ................................. 36 1. Nitrite- Borax ....................... 36 2. Molybdate-Caustic Soda...as CaCO3 . Three treatment programs developed for closed systems are: 1. Sulfite-caustic soda program 2. Nitrite- borax program 3. Molybdate-caustic

  16. Teaching Treatment Planning.

    ERIC Educational Resources Information Center

    Seligman, Linda

    1993-01-01

    Describes approach to teaching treatment planning that author has used successfully in both seminars and graduate courses. Clarifies nature and importance of systematic treatment planning, then describes context in which treatment planning seems more effectively taught, and concludes with step-by-step plan for teaching treatment planning.…

  17. Anal Cancer Treatment

    MedlinePlus

    ... cancer that remains after treatment with external-beam radiation therapy. Patients who have had treatment that saves the sphincter ... cancer remains or comes back after treatment with radiation therapy and chemotherapy. ... options. Patients who have had treatment that saves the sphincter ...

  18. Treatment Options for Myelodysplastic Syndromes

    MedlinePlus

    ... Patient Myelo-proliferative Neoplasms Patient Myelodysplastic Syndromes Treatment Myeloproliferative Neoplasms Treatment Myelodysplastic/ Myeloproliferative Neoplasms Treatment Health Professional Myelodysplastic ...

  19. Wetlands for Wastewater Treatment.

    PubMed

    Martinez-Guerra, Edith; Jiang, Yi; Lee, Gordon; Kokabian, Bahareh; Fast, Sara; Truax, Dennis D; Martin, James L; Magbanua, Benjamin S; Gude, Veera Gnaneswar

    2015-10-01

    This paper provides a review of the treatment technologies, which utilize natural processes or passive components in wastewater treatment. In particular, this paper primarily focuses on wetland systems and their applications in wastewater treatment (as an advanced treatment unit or decentralized system), nutrient and pollutant removal (single and multiple pollutants, and metals), and emerging pollutant removal (pharmaceuticals). A summary of studies involving the plant (vegetation) effects, wetland design and modeling, hybrid and innovative systems, storm water treatment and pathogen removal is also included.

  20. Refractory Hailey-Hailey disease successfully treated with sandpaper dermabrasion.

    PubMed

    LeBlanc, Keith G; Wharton, Joshua B; Sheehan, Daniel J

    2011-01-01

    A 53-year-old woman presented with a 20-year history of pruritic dermatitis on the groin, axillae, inframammary folds, posterior aspect of the neck, and popliteal fossae. She was referred to our clinic by an outside facility after results from a punch biopsy diagnosed Hailey-Hailey disease (HHD). The patient had previously attempted treatment with many traditional noninvasive options with no success. Topical treatment modalities included corticosteroids, immunomodulators, antifungals, retinoids, and antibiotic preparations. Intralesional corticosteroids, as well as botulinum toxin and carbon dioxide laser, were also unsuccessful. Failed systemic treatment modalities included antibiotics, antihistamines, prednisone, azathioprine, mycophenolate mofetil, acitretin, isotretinoin, adalimumab, and etanercept. Of note, cyclosporine was successful in clearing the cutaneous involvement in our patient, but elevation ofcreatinine and exacerbated hypertension precluded continued use. The decision was made to treat the patient by dermabrasion with sandpaper. The patient was prepped in a sterile fashion, and a field block with 1% lidocaine with epinephrine was performed. This was followed by abrasion down to the superficial dermis with 3M Sandblaster fine sandpaper (3M, St. Paul, MN) and hyfrecation between rounds ofdermabrasion. The treated areas were then covered with petrolatum and sterile gauze, and antibiotics and pain medication were prescribed. This treatment was initially performed on the patient's posterior aspect of the neck and later to the bilateral popliteal fossae and axillae. Three months post-treatment, desirable functional and cosmetic results of the treated areas had been achieved (Figure 1 and Figure 2). While no recurrence of clinically active HHD has been seen in the dermabraded areas of the neck and popliteal fossae, the patient continues to have active disease in the axillae despite sandpaper dermabrasion. To quantify our results, we performed two biopsies

  1. Land Treatment Digital Library

    USGS Publications Warehouse

    Pilliod, David S.; Welty, Justin L.

    2013-01-01

    The Land Treatment Digital Library (LTDL) was created by the U.S. Geological Survey to catalog legacy land treatment information on Bureau of Land Management lands in the western United States. The LTDL can be used by federal managers and scientists for compiling information for data-calls, producing maps, generating reports, and conducting analyses at varying spatial and temporal scales. The LTDL currently houses thousands of treatments from BLM lands across 10 states. Users can browse a map to find information on individual treatments, perform more complex queries to identify a set of treatments, and view graphs of treatment summary statistics.

  2. Cholesterol - drug treatment

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000314.htm Cholesterol - drug treatment To use the sharing features on ... treatment; Hardening of the arteries - statin Statins for Cholesterol Statins reduce your risk of heart disease, stroke, ...

  3. Radiation Oncology Treatment Team

    MedlinePlus

    ... patients to be advocates. View more information Treatment Team Quick Links Meet the Treatment Team Radiation Oncologist ... as medical oncologists and surgeons to maximize radiation’s effectiveness. Radiation oncologists are the only physicians with the ...

  4. IC Treatment: Surgical Procedures

    MedlinePlus

    ... Body-based Practices Energy Medicine Bringing Treatments to Market IC Healthcare Provider Toolkit Join the Provider Registry ... Body-based Practices Energy Medicine Bringing Treatments to Market IC Healthcare Provider Toolkit Join the Provider Registry ...

  5. IC Treatment: Antihistamines

    MedlinePlus

    ... Body-based Practices Energy Medicine Bringing Treatments to Market IC Healthcare Provider Toolkit Join the Provider Registry ... Body-based Practices Energy Medicine Bringing Treatments to Market IC Healthcare Provider Toolkit Join the Provider Registry ...

  6. Advances in Alcoholism Treatment

    PubMed Central

    Huebner, Robert B.; Kantor, Lori Wolfgang

    2011-01-01

    Researchers are working on numerous and varied approaches to improving the accessibility, quality, effectiveness, and cost-effectiveness of treatment for alcohol use disorders (AUDs). This overview article summarizes the approaches reviewed in this issue, including potential future developments for alcoholism treatment, such as medications development, behavioral therapy, advances in technology that are being used to improve treatment, integrated care of patients with AUDs and co-occurring disorders, the role of 12-step programs in the broader realm of treatment, treating patients with recurring and chronic alcohol dependence, strategies to close the gap between treatment need and treatment utilization, and how changes in the health care system may affect the delivery of treatment. This research will not only reveal new medications and behavioral therapies but also will contribute to new ways of approaching current treatment problems. PMID:23580014

  7. Treatments for Alzheimer's Disease

    MedlinePlus

    ... 3900 Find your chapter: search by state Home > Alzheimer's Disease > Treatments Overview What Is Dementia? What Is Alzheimer's? ... and move closer to a cure. Treatments for Alzheimer's disease Currently, there is no cure for Alzheimer's. But ...

  8. Malaria Treatment (United States)

    MedlinePlus

    ... Malaria Branch clinician. malaria@cdc.gov Malaria Treatment (United States) Recommend on Facebook Tweet Share Compartir Treatment of Malaria: Guidelines For Clinicians (United States) Download PDF version of Parts 1-3 formatted ...

  9. Antimicrobial Treatments and Efficacy

    EPA Science Inventory

    To limit exposure to indoor biological contamination a risk-management approach which employs various antimicrobial treatments can effectively control contaminants and reduce exposure. Antimicrobial treatment of biological contaminants, especially mold in buildings, it is often n...

  10. Pubic "Crab" Lice Treatment

    MedlinePlus

    ... please visit this page: About CDC.gov . Lice Head Lice General Information Frequently Asked Questions (FAQs) Treatment FAQs Malathion FAQs Epidemiology & Risk Factors Disease Biology Diagnosis Treatment Prevention & Control ...

  11. TENORM: Wastewater Treatment Residuals

    EPA Pesticide Factsheets

    Water and wastes which have been discharged into a municipal sewers are treated at wastewater treatment plants. These may contain both man-made and naturally occurring radionuclides which can accumulate in the treatment plant.

  12. Chickenpox Prevention and Treatment

    MedlinePlus

    ... lung disease people receiving steroid therapy pregnant women Acyclovir, an antiviral medication, is licensed for treatment of ... after the rash starts. For more information, see Acyclovir Treatment . Other antiviral medications that may also work ...

  13. The Treatment of Addiction

    ERIC Educational Resources Information Center

    Chapple, P. A. L.

    1970-01-01

    Describes sociological and medical treatment appropriate to young drug experimenters and addicts. Discusses role of teachers, probation officers, school medical services, and general practitioners. Indicates necessity for long treatment period. Considers whether dependence is a disease of delinquent behavior. (AL)

  14. HIV Treatment: The Basics

    MedlinePlus

    HIV Treatment HIV Treatment: The Basics (Last updated 2/24/2017; last reviewed 2/24/2017) Key Points Antiretroviral therapy (ART) ... reduces the risk of HIV transmission . How do HIV medicines work? HIV attacks and destroys the infection- ...

  15. Atrial Fibrillation: Treatment

    MedlinePlus

    ... this page please turn JavaScript on. Feature: Atrial Fibrillation Atrial Fibrillation: Treatment Past Issues / Winter 2015 Table of Contents Treatment for atrial fibrillation depends on how often you have symptoms, how ...

  16. Medical Treatments for Fibroids

    MedlinePlus

    ... NICHD Research Information Clinical Trials Resources and Publications Medical Treatments for Fibroids Skip sharing on social media ... Page Content Your health care provider may suggest medical treatments to reduce the symptoms of fibroids or ...

  17. Bleeding Disorders Treatment Options

    MedlinePlus

    ... Clinical Research Grant Program Epidemiological Research Treatment Safety Data Collection How You Can Help How You Can Help ... Clinical Research Grant Program Epidemiological Research Treatment Safety Data Collection How you can help How You Can Help ...

  18. Implant treatment planning considerations.

    PubMed

    Kao, Richard T

    2008-04-01

    As dental implants become a more accepted treatment modality, there is a need for all parties involved with implant dentistry to be familiar with various treatment planning issues. Though the success can be highly rewarding, failure to forecast treatment planning issues can result in an increase of surgical needs, surgical cost, and even case failure. In this issue, the focus is on implant treatment planning considerations.

  19. Multimodal treatment of pain.

    PubMed

    Mathews, Manu

    2014-10-01

    Chronic pain is a complex disorder with extensive overlap in sensory and limbic pathways. It needs systemic therapy in addition to focused local treatment. This article discusses treatment modalities other than surgical and interventional approaches and also discusses the literature regarding these treatment modalities, including pharmacotherapy, physical and occupational therapy, psychological approaches including cognitive behavior therapy, and other adjunctive treatments like yoga and tai chi.

  20. Treatment of internet addiction.

    PubMed

    Huang, Xui-qin; Li, Meng-chen; Tao, Ran

    2010-10-01

    Internet addiction (IA) is a prevalent, highly comorbid, and significantly impairing disorder. Although many psychotherapeutic approaches and psychotropic medications have been recommended and some of the psychotherapeutic approaches and a few pharmacotherapy strategies have been studied, treatment of IA is generally in its early stages. This article reviews theoretical descriptions of psychotherapy and the effects of psychosocial treatment and pharmacologic treatment. We also outline our own treatment model of IA.

  1. Treatment of Pediculosis Capitis

    PubMed Central

    Verma, Prashant; Namdeo, Chaitanya

    2015-01-01

    An endeavour to delineate the salient details of the treatment of head lice infestation has been made in the present article. Treatment modalities including over the counter permethrin and pyrethrin, and prescription medicines, including malathion, lindane, benzyl alcohol, spinosad are discussed. Salient features of alternative medicine and physical treatment modalities are outlined. The problem of resistance to treatment has also been taken cognizance of. PMID:26120148

  2. Guideline 3: Psychosocial Treatment.

    ERIC Educational Resources Information Center

    American Journal on Mental Retardation, 2000

    2000-01-01

    The third in seven sets of guidelines based on the consensus of experts in the treatment of psychiatric and behavioral problems in mental retardation (MR) focuses on psychosocial treatment. Guidelines cover general principles, choosing among psychosocial treatments, severity of MR and psychiatric/behavior symptoms, diagnosable disorders, target…

  3. Distributed Treatment Systems.

    PubMed

    Zgonc, David; Baideme, Matthew

    2015-10-01

    This section presents a review of the literature published in 2014 on topics relating to distributed treatment systems. This review is divided into the following sections with multiple subsections under each: constituent removal; treatment technologies; and planning and treatment system management.

  4. Seed Treatment. Manual 92.

    ERIC Educational Resources Information Center

    Missouri Univ., Columbia. Agricultural Experiment Station.

    This training manual provides information needed to meet minimum EPA standards for certification as a commercial applicator of pesticides in the seed treatment category. The text discusses pests commonly associated with seeds; seed treatment pesticides; labels; chemicals and seed treatment equipment; requirements of federal and state seed laws;…

  5. Microwave-assisted digestion using nitric acid for heavy metals and sulfated ash testing in active pharmaceutical ingredients.

    PubMed

    Pluhácek, T; Hanzal, J; Hendrych, J; Milde, D

    2016-04-01

    The monitoring of inorganic impurities in active pharmaceutical ingredients plays a crucial role in the quality control of the pharmaceutical production. The heavy metals and residue on ignition/sulfated ash methods employing microwave-assisted digestion with concentrated nitric acid have been demonstrated as alternatives to inappropriate compendial methods recommended in United States Pharmacopoeia (USP) and European Pharmacopoeia (Ph. Eur.). The recoveries using the heavy metals method ranged between 89% and 122% for nearly all USP and Ph. Eur. restricted elements as well as the recoveries of sodium sulfate spikes were around 100% in all tested matrices. The proposed microwave-assisted digestion method allowed simultaneous decomposition of 15 different active pharmaceutical ingredients with sample weigh up to 1 g. The heavy metals and sulfated ash procedures were successfully applied to the determination of heavy metals and residue on ignition/sulfated ash content in mycophenolate mofetil, nicergoline and silymarin.

  6. Non-nephronal hematuria misdiagnosed as C1q nephropathy: Look before you leap.

    PubMed

    Mandal, S N; Jha, R; Fatima, R; Swarnalata, G

    2012-05-01

    A 19-year-old male presented with persistent macroscopic hematuria for last 3 months. On initial evaluation, he was found to have minimal proteinuria, normal renal function, and normal complement with negative lupus serology. Light microscopy, immunofluorescence and electron microscopy of renal tissue confirmed the presence of C1q nephropathy. Because of poor response to immunosuppressive agent (prednisolone and mycophenolate mofetil), passage of urinary clot once and vexing persistent macroscopic hematuria, alternative diagnosis was considered. Cystourethroscopy showed urethritis of prostatic urethra. Immunosuppressives were stopped and doxycycline started to which hematuria responded dramatically. This case report illustrates that hematuria in this patient was because of undiagnosed urethritis rather than incidental C1q nephropathy.

  7. Acquired enophthalmos with systemic lupus erythematosus.

    PubMed

    Park, K R; Seo, M R; Ryu, H J; Chi, M J; Baek, H J; Choi, H J

    2016-01-01

    Ocular involvement sometimes occurs with systemic lupus erythematosus (SLE) but enophthalmos with SLE is rare. We report a case of enophthalmos with SLE. A 25-year-old male was admitted for two weeks of fever, sore throat, arthralgia, chest pain and right arm weakness with pain. We diagnosed him with SLE with malar rash, arthritis, pleural effusion, proteinuria, leukopenia, positive antinuclear antibody, anti-dsDNA, and lupus anticoagulant. The patient was prescribed high-dose prednisolone and hydroxychloroquine 400 mg. One week after discharge, he complained about a sensation of a sunken right eye. CT showed right enophthalmos, a post-inflammatory change and chronic inflammation. Proteinuria increased to 3.8 g/day after the patient stopped taking prednisolone. Cyclophosphamide therapy was administered for three months without improvement. We decided to restart prednisolone and change cyclophosphamide to mycophenolate mofetil. Proteinuria decreased but enophthalmos remains as of this reporting.

  8. [Dermatomyositis in a family of Working Kelpies].

    PubMed

    Röthig, A; Rüfenacht, S; Welle, M M; Thom, N

    2015-01-01

    Eight members of a family of Working Kelpies were presented with signs compatible with dermatomyositis. Alopecia, crusts, ulcerations of the skin, depigmentation of nasal planum and lips, onychodystrophy and atrophy of the masticatory muscles were present with varying degree. Histopathology of the skin, but not from muscles was performed in three dogs and confirmed the clinical diagnosis. Different immunomodulating drugs (steroids, cyclosporine, mycophenolate mofetil, pentoxifylline, doxycyline/niacinamid, omega-3 fatty acids and vitamin E) were used with variable success. Dermatomyositis is an immune-mediated disease and a genetic predisposition is known in humans and certain canine breeds, mainly Shetland Sheepdogs and Collies, but also for the Beauceron. The responsible genes have not been identified so far. It is assumed that the Working Kelpie derives from the Collie which could explain a hereditary predisposition in the Kelpie.

  9. Hydroxychloroquine-induced toxic hepatitis in a patient with systemic lupus erythematosus: a case report.

    PubMed

    Abdel Galil, S M

    2015-05-01

    Increased serum level of liver enzymes is a common finding in patients with systemic lupus erythematosus (SLE). Hepatotoxic drugs, viral hepatitis and fatty liver are thought to be the main causes of hepatic lesion in these patients. Our aim was to determine the cause of strikingly elevated liver enzymes in a case with systemic lupus presenting with acute abdomen. Liver enzyme abnormality was defined as a 10-fold or greater increase in aspartate aminotransferase and alanine aminotransferase. Acute toxic hepatitis was diagnosed, which rapidly returned to normal after cessation of the suspected causative medication, hydroxychloroquine, and subsequent administration of mycophenolate mofetil. Elevated liver enzymes are a major concern and should be well investigated in SLE patients.

  10. A Case of Rituximab Use as an Induction and Maintenance of Remission in ANCA-Associated Vasculitis

    PubMed Central

    Hafiz, Shahd; Albeity, Abdurahman; Almoallim, Hani

    2016-01-01

    Antineutrophil cytoplasmic antibody- (ANCA-) associated vasculitis (AAV) is a multisystem autoimmune disease affecting mainly microscopic blood vessels due to circulating autoantibodies against neutrophil cytoplasmic antigens. We report a case of a 57-year-old female patient presenting with hemoptysis, sinusitis, and conjunctivitis. Based on lung biopsy, the diagnosis of antineutrophil cytoplasmic antibody- (ANCA-) associated vasculitis (AAV) was established. She was put on rituximab as induction and maintenance therapy. She responded initially to rituximab as induction therapy but failed to respond in the maintenance course of the drug. Rituximab was stopped and mycophenolate mofetil was administered. She responded as laboratory c-ANCA titers turned negative and symptoms subsided. There are no randomized clinical trials addressing rituximab effect in induction and remission at the same time. This case report doubts the efficacy of the use of rituximab therapy for both induction and maintenance of remission at the same time, waiting for the results of the ongoing trials. PMID:27006851

  11. Common occurrence of everolimus-associated aphthous stomatitis in Japanese heart transplant recipients.

    PubMed

    Sasaoka, T; Kato, T S; Oda, N; Wada, K; Komamura, K; Asakura, M; Hashimura, K; Ishibashi-Ueda, H; Nakatani, T; Isobe, M; Kitakaze, M

    2010-11-01

    Mammalian target of rapamycin (mTOR) inhibitors display antiproliferative effects with less nephrotoxicity than calcineurin inhibitors. However, clinical use of mTOR inhibitors can be associated with a series of adverse events. We experienced cases of aphthous stomatitis associated with everolimus (EVL) in four Japanese heart transplant recipients treated at the target trough EVL blood level after a switch from mycophenolate mofetil between April and December 2007. All four patients developed aphthous stomatitis; three required reduction of the exposure and one, EVL discontinuation due to stomatitis as well as other side effects. All patients recovered from stomatitis after reduction or withdrawal of EVL. Thus, we considered that EVL-related stomatitis might occur commonly among the Japanese population. The proper dosage, effects, and frequency of the side effects of mTOR inhibitors may vary by ethnic population.

  12. Behçet's syndrome in pregnancy

    PubMed Central

    Martineau, Marcus; Haskard, Dorian O; Nelson-Piercy, Catherine

    2010-01-01

    Behçet's syndrome (BS), a systemic inflammatory disease characterized by oral and genital ulceration, eye inflammation and arthritis, usually presents in the third and fourth decades of life, but is rare in pregnancy. BS is not usually associated with a detrimental effect on pregnancy outcome. In most women BS is reported to improve in pregnancy, although it may not always follow a similar course in successive pregnancies and it is not possible to predict the course of BS in a particular pregnancy. Many of the drug therapies used to treat BS are safe to use in pregnancy and in the breastfeeding mother. These include corticosteroids, azathioprine, calcineurin inhibitors and probably colchicine. Experience with use of biologics in pregnancy is increasing. Drugs used in the management of BS that should be avoided in women planning a pregnancy include methotrexate, mycophenolate mofetil, thalidomide, cyclophosphamide and chlorambucil. PMID:27582833

  13. Systemic Immunomodulatory Strategies in High-risk Corneal Transplantation

    PubMed Central

    Abud, Tulio B.; Di Zazzo, Antonio; Kheirkhah, Ahmad; Dana, Reza

    2017-01-01

    The cornea is the most commonly transplanted tissue in the body. Although corneal grafts generally have high success rates, transplantation onto inflamed and vascularized host beds, or so-called high-risk corneal transplantation, has a high rate of graft rejection. The management of this high-risk corneal transplantation is challenging and involves numerous measures. One of the key measures to prevent graft rejection in these cases is the use of systemic immunosuppressive agents. In this article, we will review the systemic immunosuppressive agents most commonly used for high-risk corneal transplantation, which include corticosteroids, cysclosporine A, tacrolimus, mycophenolate mofetil, and rapamycin. Benefits, risks, and published data on the use of these medications for high-risk corneal transplantation will be detailed. We will also summarize novel immunoregulatory approaches that may be used to prevent graft rejection in high-risk corneal transplantation. PMID:28299010

  14. Neuropsychiatric Systemic Lupus Erythematosus: A Diagnostic Conundrum

    PubMed Central

    Joseph, Vivek; Anil, Rahul; Aristy, Sary

    2016-01-01

    A 70-year-old man presented with complaints of rapid cognitive decline and new onset leukopenia. The patient had a 17-year history of refractory seizures. Detailed review of symptoms and investigations revealed the patient met American College of Rheumatology (ACR) diagnostic criteria for systemic lupus erythematosus (SLE). The patient had high titer ANA with a strongly positive dsDNA. Immunosuppressive therapy with hydroxychloroquine and mycophenolate mofetil led to significant improvement in cognition and seizures. Neuropsychiatric SLE should be considered a potential differential diagnosis for patients presenting with seizures or cognitive decline. Moreover, neuropsychiatric manifestations especially seizures are an early event in the disease course of SLE. Hence, we believe that early diagnosis of SLE by neuropsychiatric manifestations will not only lead to better control of CNS symptoms but early immunosuppressive therapy could control the progression of the underlying autoimmune disease. PMID:27635183

  15. Systemic Immunomodulatory Strategies in High-risk Corneal Transplantation.

    PubMed

    Abud, Tulio B; Di Zazzo, Antonio; Kheirkhah, Ahmad; Dana, Reza

    2017-01-01

    The cornea is the most commonly transplanted tissue in the body. Although corneal grafts generally have high success rates, transplantation onto inflamed and vascularized host beds, or so-called high-risk corneal transplantation, has a high rate of graft rejection. The management of this high-risk corneal transplantation is challenging and involves numerous measures. One of the key measures to prevent graft rejection in these cases is the use of systemic immunosuppressive agents. In this article, we will review the systemic immunosuppressive agents most commonly used for high-risk corneal transplantation, which include corticosteroids, cysclosporine A, tacrolimus, mycophenolate mofetil, and rapamycin. Benefits, risks, and published data on the use of these medications for high-risk corneal transplantation will be detailed. We will also summarize novel immunoregulatory approaches that may be used to prevent graft rejection in high-risk corneal transplantation.

  16. Influence of SDZ RAD vs. MMF on gastric emptying in renal transplant recipients.

    PubMed

    Maes, Bart D; Evenepoel, Pieter; Kuypers, Dirk; Geypens, Benny; Ghoos, Yvo; Vanrenterghem, Yves

    2003-06-01

    SDZ RAD and mycophenolate mofetil (MMF) are increasingly used in the prevention of renal allograft rejection. SDZ RAD, having a macrolide structure, and MMF, known with gastrointestinal side-effects, may have gastric motility modifying properties. Gastric emptying was examined 1 yr after renal transplantation in eight patients taking corticosteroids (CS), cyclosporin A (CsA) and SDZ RAD and six patients treated with CS, CsA and MMF. Comparing the two groups, no significant differences in gastric emptying of solids and liquids were noted. Compared with normal volunteers, solid gastric emptying was faster in the SDZ RAD group and similar in the MMF group. It is concluded that in stable renal transplant recipients treated with MMF, gastric emptying was normal. Because of the impact on drug absorption and gastrointestinal symptoms, further studies are indicated to corroborate the potential prokinetic properties of SDZ RAD.

  17. Adjuvant drugs in autoimmune bullous diseases, efficacy versus safety: Facts and controversies.

    PubMed

    Schiavo, Ada Lo; Puca, Rosa Valentina; Ruocco, Vincenzo; Ruocco, Eleonora

    2010-01-01

    During the last decades, the conventional therapy for autoimmune blistering diseases has been high-dose, long-term systemic corticosteroid and immunosuppressive agents or adjuvant drugs. Long-term, high-dose steroid therapy can result in serious adverse effects. The rationale for using adjuvant drugs is that concerns reducing the need for corticosteroids, and hence, their side effects, or it may result in better control of the disease, or both. Immunosuppressive agents are not free of adverse effects, however. Prolonged immune suppression may account for high rates of morbidity, disability, and possible death. There is no consensus about the first-choice adjuvant drug for the management of blistering autoimmune diseases. This contribution evaluates six adjuvant drugs-cyclophosphamide, azathioprine, cyclosporine, mycophenolate mofetil, intravenous immunoglobulin, and rituximab-and discusses the choice of a "winning drug" that is effective and safe.

  18. Wetlands for Wastewater Treatment.

    PubMed

    Jiang, Yi; Martinez-Guerra, Edith; Gnaneswar Gude, Veera; Magbanua, Benjamin; Truax, Dennis D; Martin, James L

    2016-10-01

    An update on the current research and development of the treatment technologies, which utilize natural processes or passive components in wastewater treatment, is provided in this paper. The main focus is on wetland systems and their applications in wastewater treatment (as an advanced treatment unit or decentralized system), nutrient and pollutant removal (metals, industrial and emerging pollutants including pharmaceutical compounds). A summary of studies involving the effects of vegetation, wetland design and modeling, hybrid and innovative systems, storm water treatment and pathogen removal is also included.

  19. A randomized, controlled trial of everolimus-based dual immunosuppression versus standard of care in de novo kidney transplant recipients.

    PubMed

    Chadban, Steven J; Eris, Josette Marie; Kanellis, John; Pilmore, Helen; Lee, Po Chang; Lim, Soo Kun; Woodcock, Chad; Kurstjens, Nicol; Russ, Graeme

    2014-03-01

    Kidney transplant recipients receiving calcineurin inhibitor-based immunosuppression incur increased long-term risks of cancer and kidney fibrosis. Switch to mammalian target of rapamycin (mTOR) inhibitors may reduce these risks. Steroid or Cyclosporin Removal After Transplant using Everolimus (SOCRATES), a 36-month, prospective, multinational, open-label, randomized controlled trial for de novo kidney transplant recipients, assessed whether everolimus switch could enable elimination of mycophenolate plus either steroids or CNI without compromising efficacy. Patients received cyclosporin, mycophenolate and steroids for the first 14 days then everolimus with mycophenolate and CNIwithdrawal (CNI-WD); everolimus with mycophenolate and steroid withdrawal (steroid-WD); or cyclosporin, mycophenolate and steroids (control). 126 patients were randomized. The steroid WD arm was terminated prematurely because of excess discontinuations. Mean eGFR at month 12 for CNI-WD versus control was 65.1 ml/min/1.73 m2 vs. 67.1 ml/min/1.73 m2 by ITT, which met predefined noninferiority criteria (P=0.026). The CNI-WD group experienced a higher rate of BPAR(31% vs. control 13%, P=0.048) and showed a trend towards higher composite treatment failure (BPAR, graft loss, death, loss to follow-up). The 12 month results from SOCRATES show noninferiority in eGFR, but a significant excess of acute rejection when everolimus was commenced at week 2 to enable a progressive withdrawal of mycophenolate and cyclosporin in kidney transplant recipients.

  20. Quantification and Comparison of Anti-Fibrotic Therapies by Polarized SRM and SHG-Based Morphometry in Rat UUO Model

    PubMed Central

    Weldon, Steve M.; Matera, Damian; Lee, ChungWein; Yang, Haichun; Fryer, Ryan M.; Fogo, Agnes B.; Reinhart, Glenn A.

    2016-01-01

    Renal interstitial fibrosis (IF) is an important pathologic manifestation of disease progression in a variety of chronic kidney diseases (CKD). However, the quantitative and reproducible analysis of IF remains a challenge, especially in experimental animal models of progressive IF. In this study, we compare traditional polarized Sirius Red morphometry (SRM) to novel Second Harmonic Generation (SHG)-based morphometry of unstained tissues for quantitative analysis of IF in the rat 5 day unilateral ureteral obstruction (UUO) model. To validate the specificity of SHG for detecting fibrillar collagen components in IF, co-localization studies for collagens type I, III, and IV were performed using IHC. In addition, we examined the correlation, dynamic range, sensitivity, and ability of polarized SRM and SHG-based morphometry to detect an anti-fibrotic effect of three different treatment regimens. Comparisons were made across three separate studies in which animals were treated with three mechanistically distinct pharmacologic agents: enalapril (ENA, 15, 30, 60 mg/kg), mycophenolate mofetil (MMF, 2, 20 mg/kg) or the connective tissue growth factor (CTGF) neutralizing antibody, EX75606 (1, 3, 10 mg/kg). Our results demonstrate a strong co-localization of the SHG signal with fibrillar collagens I and III but not non-fibrillar collagen IV. Quantitative IF, calculated as percent cortical area of fibrosis, demonstrated similar response profile for both polarized SRM and SHG-based morphometry. The two methodologies exhibited a strong correlation across all three pharmacology studies (r2 = 0.89–0.96). However, compared with polarized SRM, SHG-based morphometry delivered a greater dynamic range and absolute magnitude of reduction of IF after treatment. In summary, we demonstrate that SHG-based morphometry in unstained kidney tissues is comparable to polarized SRM for quantitation of fibrillar collagens, but with an enhanced sensitivity to detect treatment-induced reductions in

  1. Treatment of bipolar disorder

    PubMed Central

    2013-01-01

    We review recent developments in the acute and long-term treatment of bipolar disorder and identify promising future routes to therapeutic innovation. Overall, advances in drug treatment remain quite modest. Antipsychotic drugs are effective in the acute treatment of mania; their efficacy in the treatment of depression is variable with the clearest evidence for quetiapine. Despite their widespread use, considerable uncertainty and controversy remains about the use of antidepressant drugs in the management of depressive episodes. Lithium has the strongest evidence for long-term relapse prevention; the evidence for anticonvulsants such as divalproex and lamotrigine is less robust and there is much uncertainty about the longer term benefits of antipsychotics. Substantial progress has been made in the development and assessment of adjunctive psychosocial interventions. Long-term maintenance and possibly acute stabilisation of depression can be enhanced by the combination of psychosocial treatments with drugs. The development of future treatments should consider both the neurobiological and psychosocial mechanisms underlying the disorder. We should continue to repurpose treatments and to recognise the role of serendipity. We should also investigate optimum combinations of pharmacological and psychotherapeutic treatments at different stages of the illness. Clarification of the mechanisms by which different treatments affect sleep and circadian rhythms and their relation with daily mood fluctuations is likely to help with the treatment selection for individual patients. To be economically viable, existing psychotherapy protocols need to be made briefer and more efficient for improved scalability and sustainability in widespread implementation. PMID:23663953

  2. Treatment for morbid obesity

    PubMed Central

    Carmichael, A

    1999-01-01

    There is no single unifying theory to explain the aetiology of obesity but several environmental factors, such as decreased physical activity and increased fat intake may contribute to its development in genetically predisposed individuals. Dietary and pharmacological treatments of morbid obesity have been proven to be unsuccessful. Modern surgical treatments have been shown to be effective in achieving significant weight loss with consequent reduction in morbidity. Despite the fact that surgical treatment of morbid obesity is the only therapeutic form that has stood the test of time, it still remains a crisis-driven form of therapy in the UK. It is probable that a better understanding of the aetiology and physiology of obesity may lead to the development of an effective pharmacological treatment of obesity in the future. However, until then, surgical treatment of morbid obesity should be considered as an effective and efficient way of treatment in selected cases.


Keywords: obesity PMID:10396579

  3. Electrotechnologies for water treatment

    SciTech Connect

    Douglas, J.

    1993-03-01

    Water and wastewater utilities face major changes in their treatment systems as a result of recent environmental regulations. Not only do these new rules specify reduction requirements for contaminants not previously regulated, they also target the by-products of chlorination, which has been the basic disinfection technique in this country since the early days of municipal water treatment. As a result, EPRI has been working with the American Water Works Association Research Foundation and the Water Environment Research Foundation to support the development of advanced treatment alternatives and improve energy efficiency at treatment facilities. The work has identified a number of innovative, electrically based treatment technologies that provide the additional capabilities required, promote higher efficiency in treatment processes, and serve electric utilities' demand-side management objectives. 5 refs.

  4. Ebola vaccine and treatment.

    PubMed

    Takada, Ayato

    2015-01-01

    Filoviruses (Ebola and Marburg viruses) cause severe hemorrhagic fever in humans and nonhuman primates. No effective prophylaxis or treatment for filovirus diseases is yet commercially available. The recent outbreak of Ebola virus disease in West Africa has accelerated efforts to develop anti-Ebola virus prophylaxis and treatment, and unapproved drugs were indeed used for the treatment of patients during the outbreak. This article reviews previous researches and the latest topics on vaccine and therapy for Ebola virus disease.

  5. [Pollinosis: drug treatments].

    PubMed

    Harf, R

    2013-06-01

    The medical treatment of allergic rhino-conjunctivitis involves different classes of drugs administered locally or by general route. They belong to three main classes, antihistamines, steroids and mast cell stabilizers. Since it is a relatively benign and also highly common disease, treatment options are limited by possible, even mild, side effects and by cost efficacy restriction. In the more severe forms of the condition, treatment efficacy remains unsatisfactory.

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

    PubMed Central

    Xu, Xinya; Zhang, Xiaoyong; Nong, Xuhua; Wang, Jie; Qi, Shuhua

    2017-01-01

    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. PMID:28218640

  7. [Treatment of vasculitis].

    PubMed

    Novak, Srdan

    2013-01-01

    Treatment of vasculitis depends on etiology and type of vasculitis. Gluccocorticoids are drug of choice in treatment of systemic vasculitis. While in vasculitis of large vessels treatment with gluccocorticoids is often sufficient, in ANCA associated vasculitis almost always intial combination of gluccocorticoids and immunosupresive drugs (cyclofosfamide in severe forms; azatioprin and metotrrexate in moderate disease) is needed. Maintance therapy of ANCA associated vasculitis is methotrexate or azatioprin. From biologic therapy, in gigantocellular vasculitis treatment with tocilizumb has a great expectation, while in ANCA associated vasculitis recently rituximab was approved by regulatory agencies, and it is nontinferior to cyclofosfamide in induction of remission and prefarable in relapsing disease.

  8. [Treatment of acne].

    PubMed

    Delanoë, P; de Prost, Y

    1997-11-01

    The treatment of acne is based upon simple pathogenic arguments, but needs to be adapted to the type of acne. Patients must always be informed that it is long and difficult and that no significant response will be expected before 2 to 3 months of regular treatment. The authors present the different therapeutic agents and strategies. Isotretinoin should be used only in severe acne after failure of at least 3 months of a well conducted classical treatment and in nodulo-cystic acne; because of its major side effect of teratogenicity its use in adolescent girl's requires pregnancy testings before and during treatment and an effective contraception.

  9. Giardia Infection Treatment

    MedlinePlus

    ... Illness & Symptoms Diagnosis & Detection Treatment Sources of Infection & Risk ... Giardia trophozoites under scanning electron microscope. Credit: Waterborne Disease Prevention Branch, CDC Several drugs can ...

  10. Modern treatment of acromegaly

    PubMed Central

    Merza, Z

    2003-01-01

    Acromegaly is an endocrine disorder characterised by increased morbidity and mortality. It is usually caused by a growth hormone secreting pituitary adenoma and is manifested by a variety of clinical features. Surgery is usually the treatment of choice, however over the last few years, several new methods of treatment have been developed. A recent consensus on the targets for treatment has led to multiple studies being conducted to assess the efficacy of the currently available options. This review examines the evidence for and against these treatments. PMID:12743333

  11. Treatment of ankylosing spondylitis.

    PubMed

    Sari, İsmail; Öztürk, Mehmet Akif; Akkoç, Nurullah

    2015-01-01

    Ankylosing spondylitis is a chronic, inflammatory, rheumatic disease that can reduce the quality of life and increase the risk of disability and mortality. It also causes direct and indirect economic losses due to health expenses and as a result of workforce loss. Management of this disease consists of pharmacological and nonpharmacological modalities. Until recently, pharmacological treatment options have been very limited. However, development of novel biological drugs revolutionized the management of this disease. The aim of this review article is to present an updated overview of the pharmacologic treatment of ankylosing spondylitis. Nonpharmacological treatment modalities including physiotherapy and exercise are only briefly mentioned and surgical treatment is not discussed.

  12. Addison's Disease: Treatment

    MedlinePlus

    ... producing. Some options for treatment include: Oral corticosteroids. Hydrocortisone (Cortef), prednisone or cortisone acetate may be used to replace cortisol. Your doctor may prescribe fludrocortisone to replace aldosterone. ...

  13. Enterobiasis (Pinworm Infection): Treatment

    MedlinePlus

    ... About CDC.gov . Pinworm Infection General Information Pinworm Infection FAQs Epidemiology & Risk Factors Biology Disease Diagnosis Treatment Prevention & Control Resources for Health Professionals Publications Get Email Updates ...

  14. [Orthodontic treatment for adults].

    PubMed

    Kuitert, R B

    2000-04-01

    The number of adults undergoing orthodontic treatment has increased strongly and the average age that adult patients undergo orthodontic treatment increased steadily although 3/4 is still younger than 27 years. In adults the facial skeletal pattern can only be changed in a very confined way, consequently in case of an abnormal skeletal pattern one has to choose between a combined orthodontic-surgical approach (which is the case in 18% of the patients) and a compromised orthodontic treatment, if necessary combined with other disciplines. It is still controversial whether tooth movement in adults is slower and more difficult than in adolescents. The same holds true for the risk for loss of periodontal support, for root resorption, for gnathologic problems and for relapse. As related to these variables there appears to be a large individual variation. Many adults show one or more problems in their dentition that may influence their orthodontic treatment. About 60% of the adult patients need a multidisciplinary approach. The development of implantology and of bone regeneration and bone grafting has lead to more combined treatments. The risks of such complex treatment plans are generally larger than those for more simple kinds of treatment. A very careful treatment planning and good communication between the different specialists is essential. Moreover the treatment plan with all its (dis)advantages has to be extensively discussed with the patient.

  15. Noninvasive treatments for headache.

    PubMed

    Biondi, David M

    2005-05-01

    Primary headache disorders are often accompanied by neck pain or other symptoms referable to neck muscles. Therefore, physical therapy and other physical treatments are commonly prescribed for headache management. A medical literature review was completed in order to gather information regarding the efficacy of selected physical modalities in the treatment of primary and cervicogenic headache disorders. After analyzing the collected data, expert opinions were developed regarding the utility and efficacy of selected physical modalities in the management of primary and cervicogenic headaches. Based on this review, the following four expert opinions are presented: physical therapy is more effective than massage therapy or acupuncture for the treatment of tension-type headache and appears to be most beneficial for patients with a high frequency of headache attacks. Physical therapy is most effective for the treatment of migraine when combined with other treatments such as thermal biofeedback, relaxation training and exercise. Chiropractic manipulation demonstrated a trend towards benefit in the treatment of tension-type headache, but evidence is weak. Chiropractic manipulation is probably more effective in the treatment of tension-type headache than it is in the treatment of migraine. In general, strong evidence is lacking regarding the efficacy of these treatments in reducing headache frequency, intensity, duration and disability in many commonly encountered clinical situations. Many of the published case series and controlled studies are of low quality. Physical treatments are unlikely to pose a significant risk, with the exception of high velocity chiropractic manipulation of the neck. Consideration must be given to financial costs and lost treatment opportunity by prescribing potentially ineffective treatment. In the absence of clear evidence regarding their role in treatment, physicians and patients are advised to make cautious and individualized judgments about

  16. 21 CFR 312.320 - Treatment IND or treatment protocol.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Treatment IND or treatment protocol. 312.320... for Treatment Use § 312.320 Treatment IND or treatment protocol. Under this section, FDA may permit an investigational drug to be used for widespread treatment use. (a) Criteria. The criteria in § 312.305(a) must...

  17. Pharmacokinetics, Pharmacodynamics and Pharmacogenomics of Immunosuppressants in Allogeneic Haematopoietic Cell Transplantation: Part I.

    PubMed

    McCune, Jeannine S; Bemer, Meagan J

    2016-05-01

    Although immunosuppressive treatments and target concentration intervention (TCI) have significantly contributed to the success of allogeneic haematopoietic cell transplantation (alloHCT), there is currently no consensus on the best immunosuppressive strategies. Compared with solid organ transplantation, alloHCT is unique because of the potential for bidirectional reactions (i.e. host-versus-graft and graft-versus-host). Postgraft immunosuppression typically includes a calcineurin inhibitor (cyclosporine or tacrolimus) and a short course of methotrexate after high-dose myeloablative conditioning, or a calcineurin inhibitor and mycophenolate mofetil after reduced-intensity conditioning. There are evolving roles for the antithymyocyte globulins (ATGs) and sirolimus as postgraft immunosuppression. A review of the pharmacokinetics and TCI of the main postgraft immunosuppressants is presented in this two-part review. All immunosuppressants are characterized by large intra- and interindividual pharmacokinetic variability and by narrow therapeutic indices. It is essential to understand immunosuppressants' pharmacokinetic properties and how to use them for individualized treatment incorporating TCI to improve outcomes. TCI, which is mandatory for the calcineurin inhibitors and sirolimus, has become an integral part of postgraft immunosuppression. TCI is usually based on trough concentration monitoring, but other approaches include measurement of the area under the concentration-time curve (AUC) over the dosing interval or limited sampling schedules with maximum a posteriori Bayesian personalization approaches. Interpretation of pharmacodynamic results is hindered by the prevalence of studies enrolling only a small number of patients, variability in the allogeneic graft source and variability in postgraft immunosuppression. Given the curative potential of alloHCT, the pharmacodynamics of these immunosuppressants deserves to be explored in depth. Development of

  18. Spectrum and outcome of primary glomerulonephritis.

    PubMed

    Al Wakeel, Jamal S; Mitwalli, Ahmed H; Tarif, Nauman; Alam, Awatif A; Hammad, Durdana; Abu-Aisha, Hassan; Memon, Nawaz; Sulimani, Fathia; Askar, Akram; Qudsi, Abdo

    2004-01-01

    Glomerulonephritis (GN) is a major cause of chronic renal failure (CRF). To evaluate the trends and outcome with modern improved treatment strategies, we retrospectively reviewed the clinical records of 120 patients with biopsy proven primary GN at our center from January 1990 to June 2001. All the biopsy specimens were subjected to light, electron and immunofluorescent microscopy. The recorded clinical parameters included the presenting symptoms, blood pressure readings, complete blood count, urinalysis, 24-hr urinary protein excretion, creatinine clearance besides rendered therapy and the outcome. Focal segmental glomerulosclerosis was the most common GN and accounted for 56 (47.6%) cases. The frequency of other GN cases in our study included IgA GN in 21 (17.5%) patients, membranous GN in 20 (16.7%), minimal change disease (MCD) in 13 (10.8%), membranoproliferative GN in 4 (3.3%), post infection in 4 (3.3%) and rapidly progressive glomerulonephritis (RPGN) in 2 (1.7%). The type of nephropathy had great influence on outcome and response to therapy. The deterioration of patients with FSGS was the fastest of the glomerulopathies, and nine (16.1%) patients developed end-stage renal failure (ESRD). MCD and post infection GN had the best outcome. Corticosteroids alone along with supportive medication conferred good results in MCD, while combined therapies of mycophenolate mofetil (MMF) and/or cyclophosphamide with corticosteroids provided better outcomes in the rest of the GN. RPGN responded well to the cyclophosphamide and the patients did not develop ESRD. Hyperuricemia, high serum creatinine and hypertension predicted worse outcomes. The control of blood pressure and glucose, and treatment of hyperuricemia and hypoalbuminemia had salutary effect on the outcome. We conclude that due to the better delivered care the outcome of primary GN has improved over the years. However, FSGS is still the most frequently encountered primary GN and has the worst outcome. In the

  19. Adult Living Donor Liver Transplantation Across ABO-Incompatibility.

    PubMed

    Lee, Chen-Fang; Cheng, Chih-Hsien; Wang, Yu-Chao; Soong, Ruey-Shyang; Wu, Tsung-Han; Chou, Hong-Shiue; Wu, Ting-Jung; Chan, Kun-Ming; Lee, Ching-Song; Lee, Wei-Chen

    2015-10-01

    The objective of this study was to evaluate the results of adult ABO-incompatible living donor liver transplantation (LDLT).ABO-incompatible LDLT is an aggressive treatment that crosses the blood-typing barrier for saving lives from liver diseases. Although graft and patient survival have been improved recently by various treatments, the results of adult ABO-incompatible LDLT require further evaluation.Two regimens were designed based on isoagglutinin IgG and IgM titers and the time course of immunological reactions at this institute. When isoagglutinin IgG and IgM titers were ≤64, liver transplantation was directly performed and rituximab (375 mg/m) was administrated on postoperative day 1 (regimen I). When isoagglutinin titers were >64, rituximab (375 mg/m) was administered preoperatively with or without plasmapheresis and boosted on postoperative day 1 (regimen II). Immunosuppression was achieved by administration of mycophenolate mofetil, tacrolimus, and steroids.Forty-six adult ABO-incompatible and 340 ABO-compatible LDLTs were performed from 2006 to 2013. The Model for End-Stage Liver Disease scores for ABO-incompatible recipients ranged from 7 to 40, with a median of 14. The graft-to-recipient weight ratio ranged from 0.61% to 1.61% with a median of 0.91%. The 1-, 3-, and 5-year survival rates were 81.7%, 75.7%, and 71.0%, respectively, for ABO-incompatible LDLT recipients, compared to 81.0%, 75.2%, and 71.5% for ABO-C recipients (P = 0.912). The biliary complication rate was higher in ABO-incompatible LDLT recipients than in the ABO-compatible recipients (50.0% vs 29.7%, P = 0.009).In the rituximab era, the blood type barrier can be crossed to achieve adult ABO-incompatible LDLT with survival rates comparable to those of ABO-compatible LDLT, but with more biliary complications.

  20. Treatment strategies in mastocytosis.

    PubMed

    Siebenhaar, Frank; Akin, Cem; Bindslev-Jensen, Carsten; Maurer, Marcus; Broesby-Olsen, Sigurd

    2014-05-01

    Treatment recommendations for mastocytosis are based mostly on expert opinion rather than evidence obtained from controlled clinical trials. In this article, treatment options for mastocytosis are presented, with a focus on the control of mediator-related symptoms in patients with indolent disease.

  1. Psychological Treatments to Avoid

    ERIC Educational Resources Information Center

    Thomason, Timothy C.

    2010-01-01

    Certain psychological treatments should be avoided, and a list of such treatments would provide valuable guidance for counselors, as well as potential clients. It is well established that some therapies are potentially dangerous, and some fringe therapies are highly unlikely to help clients beyond a placebo effect. This article provides an…

  2. "Psychotherapy" Versus "Treatment"

    ERIC Educational Resources Information Center

    Arkowitz, Hal

    2005-01-01

    This paper presents comments on "Psychological treatments" by D. H. Barlow. Barlow proposed that we distinguish between the terms "treatment" and "psychotherapy." The author believes that not only is the distinction unnecessary, but that its implications could have negative consequences for the field of clinical psychology. It is the proposed…

  3. Nursing and Psychological Treatments

    ERIC Educational Resources Information Center

    Kwekkeboom, Kristine L.; Ameringer, Suzanne; Harrison, Tondi; Phillips, Christopher M.; Serlin, Ronald C.; Ward, Sandra E.

    2005-01-01

    This brief article presents a comment on "Psychological Treatments" by D. H. Barlow. In his article, Barlow pointed to the need "to solidify the identification of psychology as a health care profession" by changing the terminology of practice in the health care context from psychotherapy to psychological treatments and suggested that the only…

  4. Seed Treatment. Bulletin 760.

    ERIC Educational Resources Information Center

    Lowery, Harvey C.

    This manual gives a definition of seed treatment, the types of seeds normally treated, diseases and insects commonly associated with seeds, fungicides and insecticides used, types of equipment used for seed treatment, and information on labeling and coloring of treated seed, pesticide carriers, binders, stickers, and safety precautions. (BB)

  5. Treatment. Technical Assistance Packet.

    ERIC Educational Resources Information Center

    Join Together, Boston, MA.

    Treatment is one component of a strategy to reduce substance abuse. It can include detoxification; inpatient counseling; outpatient counseling; therapeutic communities; and self help groups. Referrals can take place in settings such as emergency rooms; employee assistance programs; churches; and physicians' offices. Unmet treatment needs can cause…

  6. Coping – After Treatment

    Cancer.gov

    Many cancer survivors say that once treatment ended, it was hard to make a transition to a new way of life. Learn about this phase of your care and how to adjust to the new feelings and issues that come after cancer treatment.

  7. The Treatment Philosophy Snowballs.

    ERIC Educational Resources Information Center

    Hern, Matt

    1998-01-01

    Students who respond to the ludicrous environments of schooling with behaviors and demeanor that do not fit school criteria frequently are given a medical label and drug treatment. The fact that Ritalin is given to 2.8% of all American children reflects a "treatment philosophy" in which professionals define problems and prescribe…

  8. Treatment of Evolution Inconsistent

    ERIC Educational Resources Information Center

    Cavanagh, Sean

    2005-01-01

    State standards for academic content vary enormously in how well they cover the topic of evolution, with many of those documents either ignoring or giving scant treatment to the core principles of that established scientific theory. This article presents the analysis of Education Week on state's standards treatment of evolution. Nearly all the…

  9. Assessment, Diagnosis, and Treatment.

    ERIC Educational Resources Information Center

    Mullis, Thomas

    The purpose of this paper is to provide an overview of assessment, diagnosis, and treatment planning for individuals with substance abuse problems. The intent is to provide information to professional counselors in school, rehabilitation, school psychology, social work, public mental health, and private treatment settings. Information to be…

  10. Generic phytosanitary irradiation treatments

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The history of the development of generic phytosanitary irradiation (PI) treatments is discussed beginning with its initial proposal in 1986. Generic PI treatments in use today are 150 Gy for all hosts of Tephritidae, 250 Gy for all arthropods on mango and papaya shipped from Australia to New Zeala...

  11. Invisalign in TMD treatment.

    PubMed

    Miller, David B

    2009-01-01

    The objectives of functional orthodontic treatment include creating a broad smile, pleasing facial profile, and healthy, functional occlusions and temporomandibular joints. Removable orthodontic appliances have long been used in the treatment of some temporomandibular disorders. Invisalign aligners are removable orthodontic appliances. Certain TMJ case types can be treated successfully with Invisalign.

  12. [Orthoptic treatment efficiency in convergence insufficiency treatment].

    PubMed

    Dragomir, M; Truş, L; Chirilă, D; Stîngu, C

    2001-01-01

    We studied a group of 162 patients(89 females, 73 males), with ages between 15-30 years, who complained of blurred vision at near work. 98 patients(60.4%) were diagnosed with convergence insufficiency (C.I.), the rest of 64 patients(39.6%) had: low refractive errors, heterophoria and intermittent heterotropia. Patients with convergence insufficiency were divided in 3 groups: group 1(34 patients--34.6%) were treated with orthoptic exercises and near point exercises at home, group 2 (34 patients--34.6%) were treated with only near point exercises at home and control group 3 (30 patients--30.8%) without treatment. The result of the treatment of C.I. was good at 25 patients(73.5%) of group 1, at 8 patients(23.5%) of group 2 while in group 3 at only one patient the symptoms disappeared.

  13. Eosinophilic esophagitis: current treatment.

    PubMed

    Redd, Matthew; Schey, Ron

    2013-03-01

    Eosinophilic esophagitis (EoE) is a relatively new entity with a significant amount of increased recognition over the last decade. The mainstay treatments of EoE are designed to eliminate the causative allergens or to reduce their effects on the esophageal mucosa. Common treatments include dietary modification, proton pump inhibitors, systemic and topical corticosteroids, and endoscopic treatments. As the pathogenesis of EoE is explored, new and novel treatments are being studied that target specific pathways and chemokines identified in as precipitating agents of EoE. This is a rapidly evolving field with significant ongoing research and clinical studies. Our review will therefore focus on current and novel treatment approaches to the disease.

  14. [Treatment of cluster headache].

    PubMed

    Fabre, N

    2005-07-01

    Remarkable therapeutic improvements have come forward recently for trigemino-autonomic cephalalgias. Attack treatment in cluster headache is based on sumatriptan and oxygen. Non-vasoconstrictive treatments are opening a new post-triptan era but are not yet applicable. Prophylactic treatment of cluster headache is based on verapamil and lithium. The efficacy of anti-epileptic drugs in cluster headache remains to be demonstrated. Surgical treatment aimed at the parasympathetic pathways and at the trigeminal nerve demonstrates a high rate of recurrence and adverse events and questions about the relevance of a "peripheral" target in cluster headache. The efficacy of continuous hypothalamic stimulation in patients with intractable headache constitutes a breakthrough, but must be demonstrated at a larger scale and the benefice/risk ratio must be carefully evaluated. Indomethacin still remains the gold standard in paroxysmal hemicrania treatment. Until recently SUNCT was considered an intractable condition. However there are some reports of complete relief with lamotrigine, topiramate and gabapentin.

  15. Contemporary Treatment of APL

    PubMed Central

    Cull, Elizabeth H.; Altman, Jessica K.

    2014-01-01

    Acute promyelocytic leukemia (APL) is characterized by coagulopathy, leukopenic presentation and sensitivity to anthracyclines, all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). For the last 25 years, APL has been treated with a combination of ATRA and chemotherapy for induction followed by consolidation and maintenance therapy. This general treatment approach has resulted in cure rates of 80–90%. ATO, originally approved in relapsed APL, has been incorporated into contemporary upfront treatment regimens with excellent response rates. Recent studies show that most patients with APL can be cured with ATRA and ATO alone, eliminating cytotoxic chemotherapy and resulting in superior outcomes compared to standard treatment. We will herein review historical treatment of APL, treatment considerations in specific patient populations, and therapeutic updates. PMID:24643310

  16. Contemporary treatment of APL.

    PubMed

    Cull, Elizabeth H; Altman, Jessica K

    2014-06-01

    Acute promyelocytic leukemia (APL) is characterized by coagulopathy, leukopenic presentation and sensitivity to anthracyclines, all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). For the last 25 years, APL has been treated with a combination of ATRA and chemotherapy for induction followed by consolidation and maintenance therapy. This general treatment approach has resulted in cure rates of 80-90 %. ATO, originally approved in relapsed APL, has been incorporated into contemporary upfront treatment regimens with excellent response rates. Recent studies show that most patients with APL can be cured with ATRA and ATO alone, eliminating cytotoxic chemotherapy and resulting in superior outcomes compared to standard treatment. We will herein review historical treatment of APL, treatment considerations in specific patient populations, and therapeutic updates.

  17. [Biofeedback treatment for epilepsy].

    PubMed

    Nagai, Yoko

    2014-05-01

    Pharmacological treatment is the mainstay for the treatment of epilepsy. However concerns regarding long-term side effects of drugs are increasingly voiced. Behavioral treatments including biofeedback, represents an alternative management option for the control of epilepsy. Biofeedback is a non-invasive bio-behavioral procedure through which patients can learn to gain psychophysiological control over seizures. This article will first overview seizure precipitation from a psychological perspective, and then introduce three major biofeedback treatments. Sensory motor rhythm (SMR) and slow cortical potential(SCP) biofeedback uses electroencephalographic parameters and are categorized as neurofeedback. Electrodermal activity (EDA) biofeedback focuses on modulation of peripheral sympathetic tone. The neural mechanisms underlying biofeedback treatment will be discussed in relation to thalamo-cortical regulation(of neural excitability across brain networks).

  18. Pediatric hepatitis B treatment

    PubMed Central

    Inui, Ayano; Fujisawa, Tomoo

    2017-01-01

    Although the introduction of hepatitis B vaccine has been contributing to the reduction in the prevalence of hepatitis B virus (HBV) carriers worldwide, the treatment of children with chronic HBV infection is a challenge to be addressed. HBeAg seroconversion, which induces low replication of HBV, is widely accepted as the first goal of antiviral treatment in children with chronic hepatitis B. However, spontaneous HBeAg seroconversion is highly expected in children with chronic HBV infection. Therefore, the identification of children who need antiviral treatment to induce HBeAg seroconversion is essential in the management of chronic HBV infection. Guidelines and experts’ opinion show how to identify children who should be treated and how to treat them. If decompensated cirrhosis is absent, interferon-alpha is the first-line antiviral treatment. Nucleos(t)ide analogues (NAs), such as lamivudine, adefovir, entecavir and tenofovir, are also available for the treatment of children, although the approval age differs among them. If decompensated cirrhosis is present, NAs are the first-line antivirals. When the emergence of drug-resistant HBV variants is taken into consideration, entecavir (approved for age 2 years or older) and tenofovir (age 12 years or older), which have high genetic barriers, will play a central role in the treatment of HBV infection. However, the optimal duration of NA treatment and adverse events of long-term NA treatment remain unclear in children. In resource-constrained countries and regions, the financial burden of visiting hospitals, receiving routine blood examination and purchasing antiviral drugs is heavy. Moreover, there is no clear evidence that the induction of HBeAg seroconversion by antiviral treatment prevents the progression of liver disease to cirrhosis and hepatocellular carcinoma in children with chronic HBV infection. It is thus imperative to clarify the clinical impact of antiviral treatment in children with HBV infection. PMID

  19. Treatment of Thoracolumbar Fracture

    PubMed Central

    Kim, Byung-Guk; Shin, Dong-Eun

    2015-01-01

    The most common fractures of the spine are associated with the thoracolumbar junction. The goals of treatment of thoracolumbar fracture are leading to early mobilization and rehabilitation by restoring mechanical stability of fracture and inducing neurologic recovery, thereby enabling patients to return to the workplace. However, it is still debatable about the treatment methods. Neurologic injury should be identified by thorough physical examination for motor and sensory nerve system in order to determine the appropriate treatment. The mechanical stability of fracture also should be evaluated by plain radiographs and computed tomography. In some cases, magnetic resonance imaging is required to evaluate soft tissue injury involving neurologic structure or posterior ligament complex. Based on these physical examinations and imaging studies, fracture stability is evaluated and it is determined whether to use the conservative or operative treatment. The development of instruments have led to more interests on the operative treatment which saves mobile segments without fusion and on instrumentation through minimal invasive approach in recent years. It is still controversial for the use of these treatments because there have not been verified evidences yet. However, the morbidity of patients can be decreased and good clinical and radiologic outcomes can be achieved if the recent operative treatments are used carefully considering the fracture pattern and the injury severity. PMID:25705347

  20. [Chronic migraine: treatment].

    PubMed

    Pascual, Julio

    2012-04-10

    We define chronic migraine as that clinical situation in which migraine attacks appear 15 or more days per month. Until recently, and in spite of its negative impact, patients with chronic migraine were excluded of the clinical trials. This manuscript revises the current treatment of chronic migraine. The first step should include the avoidance of potential precipitating/aggravating factors for chronic migraine, mainly analgesic overuse and the treatment of comorbid disorders, such as anxiety and depression. The symptomatic treatment should be based on the use of nonsteroidal anti-inflammatory agents and triptans (in this case < 10 days per month). It is necessary to avoid the use of combined analgesics, opioids and ergotamine-containing medications. Preventive treatment includes a 'transitional' treatment with nonsteroidal anti-inflammatory agents or steroids, while preventive treatment exerts its actions. Even though those medications efficacious in episodic migraine prevention are used, the only drugs with demonstrated efficacy in the preventive treatment of chronic migraine are topiramate and pericranial infiltrations of Onabotulinumtoxin A.

  1. Land Treatment Digital Library

    USGS Publications Warehouse

    Pilliod, David S.

    2009-01-01

    Across the country, public land managers make hundreds of decisions each year that influence landscapes and ecosystems within the lands they manage. Many of these decisions involve vegetation manipulations known as land treatments. Land treatments include activities such as removal or alteration of plant biomass, seeding burned areas, and herbicide applications. Data on these land treatments are usually stored at local offices, and gathering information across large spatial areas can be difficult. There is a need to centralize and store treatment data for Federal agencies involved in land treatments because these data are useful to land managers for policy and management and to scientists for developing sampling designs and studies. The Land Treatment Digital Library (LTDL) was created by the U.S. Geological Survey (USGS) to catalog information about land treatments on Federal lands in the western United States for all interested parties. The flexible framework of the library allows for the storage of a wide variety of data in different formats. The LTDL currently stores previously established land treatments or what often are called legacy data. The project was developed and has been refined based on feedback from partner agencies and stakeholders, with opportunity for the library holdings to expand as new information becomes available. The library contains data in text, tabular, spatial, and image formats. Specific examples include project plans and implementation reports, monitoring data, spatial data files from geographic information systems, digitized paper maps, and digital images of land treatments. The data are entered by USGS employees and are accessible through a searchable web site. The LTDL can be used to respond to information requests, conduct analyses and other forms of information syntheses, produce maps, and generate reports for DOI managers and scientists and other authorized users.

  2. Treatment decisions under ambiguity.

    PubMed

    Berger, Loïc; Bleichrodt, Han; Eeckhoudt, Louis

    2013-05-01

    Many health risks are ambiguous in the sense that reliable and credible information about these risks is unavailable. In health economics, ambiguity is usually handled through sensitivity analysis, which implicitly assumes that people are neutral towards ambiguity. However, empirical evidence suggests that people are averse to ambiguity and react strongly to it. This paper studies the effects of ambiguity aversion on two classical medical decision problems. If there is ambiguity regarding the diagnosis of a patient, ambiguity aversion increases the decision maker's propensity to opt for treatment. On the other hand, in the case of ambiguity regarding the effects of treatment, ambiguity aversion leads to a reduction in the propensity to choose treatment.

  3. [Treatment of acne].

    PubMed

    Fyrand, O

    1997-08-30

    Acne is a disfiguring disease, occurring mainly in adolescence. It is a common disorder, affecting above 80% of adolescents in some degree. 50% wish to have treatment for the condition. Acne appears in many forms; from the more common comedonal and papulopustular types to the often devastating cystic and fulminant acne. Some patients develop disfiguring scarring and keloidal reactions, which persist for the rest of their lives. With the treatment facilities available in modern medicine, acne problems can be eliminated through topical and/or systemic treatment options.

  4. Childhood Vitiligo: Treatment Paradigms

    PubMed Central

    Kanwar, Amrinder Jit; Kumaran, M Sendhil

    2012-01-01

    Childhood vitiligo differs from the adults by showing a higher incidence in females, segmental vitiligo being more common and less frequent association with other systemic autoimmune and endocrine disorders. Childhood vitiligo is often associated with a marked psychosocial and long lasting effect on the self-esteem of the affected children and their parents, hence an adequate treatment is very essential. Treatment of vitiligo is indeed a tough challenge for the dermatologists’ more so in the background of childhood vitiligo. Although multiple therapeutic modalities are available in the therapeutic armamentarium, not all can be used in children. This brief report updates regarding various therapies available in the treatment of childhood vitiligo. PMID:23248365

  5. Optical treatments for acne.

    PubMed

    Ross, E Victor

    2005-01-01

    Light-based treatments for acne are becoming increasingly commonplace in dermatology. This article reviews various light approaches in acne therapy. Methods are discussed from an anatomical and a functional perspective. The emphasis is on the practicality of treatment as well as the pros and cons of various devices. Also, a review of the recent literature is presented. The article is intended to give the reader a panoramic view of this still-young and developing area. Most likely, light-based acne treatment will receive more popularity as dermatologists learn how to integrate this type of therapy within the context of more established drug agents.

  6. Current treatments for scabies.

    PubMed

    Buffet, M; Dupin, N

    2003-04-01

    Scabies is a frequent interhuman ectoparasitic infection. Several treatments are available worldwide. There are local treatments: synthetic pyrethrins, benzyl benzoate, lindane, crotamiton. Recently a few studies were published concerning ivermectin, systemic antiparasitic agent use in onchocercosis treatment. We reviewed the literature with an evidence-based medicine method. We attempt to answer two questions in particular: what is the treatment of choice for common scabies in a patient otherwise in good health? What is the role of systemic ivermectin? We also report specific situations. Among local treatments, studies are heterogeneous according to products, countries, group of treated patients, with or without contact subjects, and the method of treatment application. There are very few high proof-level controlled studies. In France, a combination of benzyl benzoate 10% and sulfiram 2% is used most, according to professional consensus. The most studied product is the cream permethrin 5%, available in the USA and UK. Its efficacy seems slightly superior to lindane and less toxic. It is more efficient than crotamiton. There is no study comparing benzyl benzoate and permethrin. Concerning systemic ivermectin, five controlled studies showed its efficiency in common scabies. But its relative efficiency over local treatment has not been established. A few open studies showed its efficacy in institutional epidemic, profuse scabies and in HIV-positive patients. Local treatment of choice in common scabies remains to be determined among the four principal molecules. There is no study comparing permethrin or esdepallethrin to benzyl benzoate. In what cases should we prescribe crotamiton or lindane? Indication of ivermectin seems proved in common scabies and probably for HIV-positive patients. It remains to be determined if it should be prescribed in the first instance, be double or triple, be associated or not with local treatment. In case of keratotic scabies, ivermectin

  7. Successful Combined Pancreas Fourth-Kidney Third and Pancreas Third-Kidney Second Transplantation: A Case Report

    PubMed Central

    Bösmüller, Claudia; Maglione, Manuel; Margreiter, Christian; Dziodzio, Tomasz; Biebl, Matthias; Pratschke, Johann; Öllinger, Robert; Öfner, Dietmar; Schneeberger, Stefan

    2015-01-01

    Background Extremely few reports have been published on experience with multiple combined pancreas-kidney re-transplantation including long-term results. We here analyze our experience with two patients following successful combined pancreas fourth-kidney third and pancreas third-kidney second transplantation. Methods Patient and graft survival as well as graft function and major complications were recorded. Patient 1 (women, 47 years) underwent combined pancreas fourth-kidney third transplantation after previous removal o