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Revisiones-Clínica-Epidemiología, Higiene & Prevención *** Reviews-Clinical-Epidemiology, Hygiene & Prevention

 

AGENTES INMUNOSUPRESORES *** IMMUNOSUPPRESSIVE COMPOUNDS

(Conceptos / Keywords: Immunosuppressive comp; Muromonab-cd3; Sirolimus; Tacrolimus; Cyclosporine; Mycophenolic acid; Antilymphocyte serum; Immunosuppressive comp. used in oncology, etc).

 

Enero / January 2001 --- Marzo / March 2004

 

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Enlace / Link

 

[1]

TÍTULO / TITLE:  - Interleukin-2 receptor monoclonal antibodies in renal transplantation: meta-analysis of randomised trials.

REVISTA / JOURNAL:  - British Medical J (BMJ). Acceso gratuito al texto completo.

      ●● Enlace a la Editora de la Revista http://bmj.com/search.dtl 

      ●● Cita: British Medical J. (BMJ): <> 2003 Apr 12;326(7393):789.

      ●● Enlace al texto completo (gratuito o de pago) 1136/bmj.326.7393.789

AUTORES / AUTHORS:  - Adu D; Cockwell P; Ives NJ; Shaw J; Wheatley K

INSTITUCIÓN / INSTITUTION:  - Department of Nephrology, Queen Elizabeth Hospital, Birmingham, B15 2TH. dwomoa.adu@uhb.nhs.uk

RESUMEN / SUMMARY:  - OBJECTIVE: To study the effect of interleukin-2 receptor monoclonal antibodies on acute rejection episodes, graft loss, deaths, and rate of infection and malignancy in patients with renal transplants. DESIGN: Meta-analysis of published data. DATA SOURCES: Medline, Embase, and Cochrane library for years 1996-2003 plus search of medical editors’ trial amnesty and contact with manufacturers of the antibodies. SELECTION OF STUDIES: Randomised controlled trials comparing interleukin-2 receptor antibodies with placebo or no additional treatment in patients with renal transplants receiving ciclosporin based immunosuppression. RESULTS: Eight randomised controlled trials involving 1871 patients met the selection criteria (although only 1858 patients were analysed). Interleukin-2 receptor antibodies significantly reduced the risk of acute rejection (odds ratio 0.51, 95% confidence interval 0.42 to 0.63). There were no significant differences in the rate of graft loss (0.78, 0.58 to 1.04), mortality (0.75, 0.46 to 1.23), overall incidence of infections (0.97, 0.77 to 1.24), incidence of cytomegalovirus infections (0.81, 0.62 to 1.04), or risk of malignancies at one year (0.82, 0.39 to 1.70). The different antibodies had a similar sized effect on acute rejection (test for heterogeneity P=0.7): anti-Tac (0.37, 0.16 to 0.89), BT563 (0.37, 0.1 to 1.38), basiliximab (0.56, 0.44 to 0.72), and daclizumab (0.46, 0.32 to 0.67). The reduction in acute rejections was similar for all ciclosporin based immunosuppression regimens (test for heterogeneity P=1.0). CONCLUSIONS: Adding interleukin-2 receptor antibodies to ciclosporin based immunosuppression reduces episodes of acute rejection at six months by 49%. There is no evidence of an increased risk of infective complications. Longer follow up studies are needed to confirm whether interleukin-2 receptor antibodies improve long term graft and patient survival.

 

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[2]

TÍTULO / TITLE:  - Novel therapeutic molecular targets for prostate cancer: the mTOR signaling pathway and epidermal growth factor receptor.

REVISTA / JOURNAL:  - J Urol 2004 Feb;171(2 Pt 2):S41-3; discussion S44.

      ●● Enlace al texto completo (gratuito o de pago) 1097/01.ju.0000108100.53239.b7

AUTORES / AUTHORS:  - Tolcher AW

INSTITUCIÓN / INSTITUTION:  - Director Clinical Research, Institute for Drug Development Cancer Therapy and Research Center, San Antonio, Texas, USA.

RESUMEN / SUMMARY:  - PURPOSE: The scientific rationale and existing evidence for the use of novel molecular targets in the chemoprevention of cancer are reviewed, with special attention to prostate cancer. MATERIALS AND METHODS: A search for relevant literature on basic science and clinical trials was conducted using PubMed/MEDLINE. RESULTS: The emergence of molecularly targeted therapies for advanced malignancies creates an important opportunity to examine these agents for the chemoprevention of prostate cancer. Two critical targets in the proliferation and malignant transformation of normal cells, the PI3/Akt signal transduction pathway and the epidermal growth factor receptor, are currently the focus of several novel investigational therapies that are in late stage phase II and phase III studies. CONCLUSIONS: Research to date supports consideration of these novel molecular targets as future agents in the chemoprevention of prostate cancer.  N. Ref:: 28

 

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[3]

TÍTULO / TITLE:  - Drug-eluting stents in vascular intervention.

REVISTA / JOURNAL:  - Lancet 2003 Jan 18;361(9353):247-9.

AUTORES / AUTHORS:  - Fattori R; Piva T

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Cardiovascular Unit, University Hospital S Orsola, 40138, Bologna, Italy. ross@med.unibo.it

RESUMEN / SUMMARY:  - CONTEXT: Restenosis is the most important long-term limitation of stent implantation for coronary artery disease, occurring in 15-60% of patients. In-stent restenosis, a refractory coronary lesion resulting from neointimal hyperplasia, challenges both vascular biologist and interventional cardiologist. Various drugs and devices have been used tried to overcome restenosis but are not particularly successful. Over 1500000 percutaneous coronary interventions are done annually. Restenosis is not only important clinically but also for its impact on health-care costs. STARTING POINT: Growth and migration of vascular smooth-muscle cells result in neointimal proliferation after vascular injury and are the key mechanism of in-stent restenosis. The rationale of the most recent approaches to restenosis (eg, brachytherapy and immunosuppressive agents) arises from the similarity between tumour-cell growth and the benign tissue proliferation which characterises intimal hyperplasia. Several immunosuppressants have been tested for their potential to inhibit restenosis, with the novel strategy of administering the drug via a coated stent platform. Local drug delivery achieves higher tissue concentrations of drug without systemic effects, at a precise site and time. The first multicentre trial with stents coated with sirolimus was by Marie-Claude Morice and colleagues (N Engl J Med 2002; 346: 1773-80). In a trial of 238 patients, restenosis of 50% or more at 6 months was 0% and 27% with sirolimus or normal stents (p<0.001), respectively, after percutaneous revascularisation. Muzaffer Degertekin and colleagues (Circulation 2002; 106: 1610-13) present data on 2-year follow-up of 15 patients who had been implanted with the sirolimus stent in another study, and confirm persistent inhibition of restenosis and an absence of unexpected adverse events. WHERE NEXT? Local application of antiproliferative agents is a promising technique and research is developing. Other agents with potential benefits (eg, statins, local gene-therapy, adenovirus-mediated arterial gene-transfer, L-arginine, abciximab, angiopeptin, recombinant pegylated hirudin, and hiloprost) as well as improvements in polymer technology (biodegradable smart polymers, coatings for multiple-drug release) are under evaluation. The clinical impact of the elimination of restenosis may influence the approach to coronary artery disease, the future of cardiac surgery, and health-care economics in cardiology.  N. Ref:: 22

 

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[4]

TÍTULO / TITLE:  - Treatment of chronic granulomatous disease with myeloablative conditioning and an unmodified hemopoietic allograft: a survey of the European experience, 1985-2000.

REVISTA / JOURNAL:  - Blood. Acceso gratuito al texto completo a partir de 1 año de la fecha de publicación.

      ●● Enlace a la Editora de la Revista http://www.bloodjournal.org/ 

      ●● Cita: Blood: <> 2002 Dec 15;100(13):4344-50. Epub 2002 Aug 8.

      ●● Enlace al texto completo (gratuito o de pago) 1182/blood-2002-02-0583

AUTORES / AUTHORS:  - Seger RA; Gungor T; Belohradsky BH; Blanche S; Bordigoni P; Di Bartolomeo P; Flood T; Landais P; Muller S; Ozsahin H; Passwell JH; Porta F; Slavin S; Wulffraat N; Zintl F; Nagler A; Cant A; Fischer A

INSTITUCIÓN / INSTITUTION:  - European Group for Blood and Marrow Transplantation (EBMT) and the European Society for Immunodeficiencies (ESID), Division of Immunology/Hematology, University Children’s Hospital, Zurich, Switzerland. reinhard.seger@kispi.unizh.ch

RESUMEN / SUMMARY:  - Treatment of chronic granulomatous disease (CGD) with myeloablative bone marrow transplantation is considered risky. This study investigated complications and survival according to different risk factors present at transplantation. The outcomes of 27 transplantations for CGD, from 1985 to 2000, reported to the European Bone Marrow Transplant Registry for primary immunodeficiencies were assessed. Most transplant recipients were children (n = 25), received a myeloablative busulphan-based regimen (n = 23), and had unmodified marrow allografts (n = 23) from human leukocyte antigen (HLA)-identical sibling donors (n = 25). After myeloablative conditioning, all patients fully engrafted with donor cells; after myelosuppressive regimens, 2 of 4 patients fully engrafted. Severe (grade 3 or 4) graft-versus-host disease (GVHD) disease developed in 4 patients: 3 of 9 with pre-existing overt infection, 1 of 2 with acute inflammatory disease. Exacerbation of infection during aplasia was observed in 3 patients; inflammatory flare at the infection site during neutrophil engraftment in 2: all 5 patients belonged to the subgroup of 9 with pre-existing infection. Overall survival was 23 of 27, with 22 of 23 cured of CGD (median follow-up, 2 years). Survival was especially good in patients without infection at the moment of transplantation (18 of 18). Pre-existing infections and inflammatory lesions have cleared in all survivors (except in one with autologous reconstitution). Myeloablative conditioning followed by transplantation of unmodified hemopoietic stem cells, if performed at the first signs of a severe course of the disease, is a valid therapeutic option for children with CGD having an HLA-identical donor.  N. Ref:: 30

 

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[5]

TÍTULO / TITLE:  - Pregnancy outcome after cyclosporine therapy during pregnancy: a meta-analysis.

REVISTA / JOURNAL:  - Transplantation 2001 Apr 27;71(8):1051-5.

AUTORES / AUTHORS:  - Bar Oz B; Hackman R; Einarson T; Koren G

INSTITUCIÓN / INSTITUTION:  - The Motherisk Program, Division of Clinical Pharmacology/Toxicology, The Hospital for Sick Children, Toronto, Ontario, Canada.

RESUMEN / SUMMARY:  - BACKGROUND: Cyclosporine (CsA) therapy must often be continued during pregnancy to maintain maternal health in such conditions as organ transplantation and autoimmune disease. This meta-analysis was performed to determine whether CsA exposure during pregnancy is associated with an increased risk of congenital malformations, preterm delivery, or low birthweight. METHODS: Various health science databases were searched to identify relevant articles. Articles selected for inclusion in the study were required to be free of any apparent selection bias and report outcomes in at least 10 newborns exposed to CsA in utero, specifically commenting on the presence or absence of congenital malformations. Article selection and data extraction were performed by two independent reviewers, with adjudication in cases of disagreement. To assess risks of CsA exposure, a summary odds ratio was calculated. Prevalence of malformations was calculated as a rate for all cyclosporine-exposed live births and for the subgroups identified. Ninety-five percent confidence intervals were constructed for both the odds ratio and prevalence rates. RESULTS: Fifteen studies (6 with control groups of transplant without use of cyclosporine; total patients: 410) met the inclusion criteria for major malformations, 10 for preterm delivery (4 with control groups; total patients: 379) and 5 for low birth weight (1 with control groups; total number of patients: 314). The calculated odds ratio of 3.83 for malformations did not achieve statistical significance (CI 0.75-19.6). The overall prevalence of major malformations in the study population (4.1%) also did not vary substantially from that reported in the general population. OR for prematurity [1.52 (CI 1.00-2.32)] did not reach statistical significance although the overall prevalence rate was 56.3%. The OR for low birth weight [1.5 (CI 0.95-2.44 based on 1 study)]. CONCLUSIONS: CsA does not appear to be a major human teratogen. It may be associated with increased rates of prematurity. More research is needed to evaluate whether cyclosporine increases teratogenic risk.

 

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[6]

TÍTULO / TITLE:  - Posttransplantation diabetes: a systematic review of the literature.

REVISTA / JOURNAL:  - Diabetes Care. Acceso gratuito al texto completo a partir de 1 año de la fecha de publicación.

      ●● Enlace a la Editora de la Revista http://care.diabetesjournals.org/ 

      ●● Cita: Diabetes Care: <> 2002 Mar;25(3):583-92.

AUTORES / AUTHORS:  - Montori VM; Basu A; Erwin PJ; Velosa JA; Gabriel SE; Kudva YC

INSTITUCIÓN / INSTITUTION:  - Division of Endocrinology, Diabetes, Metabolism, Nutrition, and Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.

RESUMEN / SUMMARY:  - OBJECTIVES: To systematically review the incidence of posttransplantation diabetes (PTD), risk factors for its development, prognostic implications, and optimal management. RESEARCH DESIGN AND METHODS: We searched databases (MEDLINE, EMBASE, the Cochrane Library, and others) from inception to September 2000, reviewed bibliographies in reports retrieved, contacted transplantation experts, and reviewed specialty journals. Two reviewers independently determined report inclusion (original studies, in all languages, of PTD in adults with no history of diabetes before transplantation), assessed study methods, and extracted data using a standardized form. Meta-regression was used to explain between-study differences in incidence. RESULTS: Nineteen studies with 3,611 patients were included. The 12-month cumulative incidence of PTD is lower (<10% in most studies) than it was 3 decades ago. The type of immunosuppression explained 74% of the variability in incidence (P = 0.0004). Risk factors were patient age, nonwhite ethnicity, glucocorticoid treatment for rejection, and immunosuppression with high-dose cyclosporine and tacrolimus. PTD was associated with decreased graft and patient survival in earlier studies; later studies showed improved outcomes. Randomized trials of treatment regimens have not been conducted. CONCLUSIONS: Physicians should consider modification of immunosuppressive regimens to decrease the risk of PTD in high-risk transplant recipients. Randomized trials are needed to evaluate the use of oral glucose-lowering agents in transplant recipients, paying particular attention to interactions with immunosuppressive drugs.  N. Ref:: 79

 

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[7]

TÍTULO / TITLE:  - Calcineurin inhibition and cardiac hypertrophy: a matter of balance.

REVISTA / JOURNAL:  - Proc Natl Acad Sci U S A. Acceso gratuito al texto completo a partir de los 6 meses de la fecha de publicación.

      ●● Enlace a la Editora de la Revista http://www.pnas.org/ 

      ●● Cita: Proc Natl Acad Sci USA (PNAS): <> 2001 Mar 13;98(6):2947-9.

      ●● Enlace al texto completo (gratuito o de pago) 1073/pnas.051033698

AUTORES / AUTHORS:  - Leinwand LA

INSTITUCIÓN / INSTITUTION:  - Department of Molecular, Cellular, and Developmental Biology, Porter Addition, Room A3B40, University of Colorado, Boulder, CO 80309-0347, USA. leinwand@stripe.colorado.edu  N. Ref:: 18

 

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[8]

TÍTULO / TITLE:  - Mycophenolate mofetil for the prevention and treatment of graft-versus-host disease following stem cell transplantation: preliminary findings.

REVISTA / JOURNAL:  - Bone Marrow Transplant 2001 Jun;27(12):1255-62.

AUTORES / AUTHORS:  - Vogelsang GB; Arai S

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, Johns Hopkins Oncology Center, Baltimore, MD 21287-8943, USA.

RESUMEN / SUMMARY:  - The therapeutic benefits of allogeneic stem cell transplantation in patients with hematologic disorders are limited by the significant morbidity and mortality of graft-versus-host disease (GVHD). Current agents for the prevention and treatment of GVHD have limited efficacy and often result in toxic side-effects. Mycophenolate mofetil (MMF) is a new immunosuppressant with a selective mechanism of action. When employed following solid organ transplantation, MMF reduces the incidence and severity of acute rejection episodes. By selectively targeting activated lymphocytes, the active metabolite of MMF, mycophenolic acid (MPA), appears to augment the actions of standard immunosuppressant agents without adding overlapping toxicities. Studies of combination regimens that include MMF report that this agent permits a dose reduction of cyclosporine, tacrolimus, or corticosteroid, without increasing the incidence of acute rejection in solid organ transplants. Reports on the efficacy of MMF following stem cell transplantation in animal studies were mixed. However, the use of a non-myeloablative conditioning regimen with a post-graft immunosuppressive regimen of MMF and cyclosporine was able to sustain stable mixed chimeras in 60% to 80% of dogs who received hematopoietic grafts from DLA-identical littermates. MMF has demonstrated activity in preliminary clinical trials for GVHD prophylaxis, and treatment of acute or chronic GVHD. Larger clinical trials are warranted to determine the optimum dose and route of MMF administration for GVHD, as well as the comparative safety and efficacy of MMF-containing regimens.  N. Ref:: 36

 

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[9]

TÍTULO / TITLE:  - Prevention by dietary (n-6) polyunsaturated phosphatidylcholines of intrahepatic cholestasis induced by cyclosporine A in animals.

REVISTA / JOURNAL:  - Life Sci 2003 Jun 13;73(4):381-92.

AUTORES / AUTHORS:  - Chanussot F; Benkoel L

INSTITUCIÓN / INSTITUTION:  - INSERM U. 476, Faculte de Medecine, 27 bd Jean Moulin, 13385 Marseille cedex 05, France. Francoise.Chanussot@medecine.univ-mrs.fr

RESUMEN / SUMMARY:  - Previous findings showed that dietary (n-6) polyunsaturated phosphatidylcholines (vegetable lecithin) could efficiently prevent intrahepatic cholestasis induced by cyclosporine A in rats. Mechanistic studies showed that expressions in rat liver of Na(+), K(+)-ATPase, Ca(2+), Mg(2+)-ATPase and F-actin were both decreased by drug administration and both enhanced by (n-6) lecithin enriched diet. There is a possible direct effect of phosphatidylcholines, vectors of polyunsaturated fatty acids provided by the metabolism of the dietary lecithin, on the aforesaid hepatic parameters. Such modulations by drug and diet result in reversed modifications of membrane composition and fluidity. Final outcome is decreased and enhanced bile lipid secretion by cyclosporine and vegetable lecithin enriched diet respectively. Moreover, we advance the hypothesis of a bypass process including a separate and functional actin-independent way for the non micellar and phospholipid-dependent secretion of bile lipids. The relationships between the ATPases, the microfilament components such as F-actin and the different transporters still remain to be clarified. Furthermore, one can speculate on beneficial effects in humans of diets enriched in vegetable lecithins that might prevent cholestasis induced by cyclosporine A.  N. Ref:: 75

 

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[10]

TÍTULO / TITLE:  - A benefit-risk assessment of basiliximab in renal transplantation.

REVISTA / JOURNAL:  - Drug Saf. Acceso gratuito al texto completo.

      ●● Enlace a la Editora de la Revista http://www.csmwm.org/ 

      ●● Cita: Drug Safety: <> 2004;27(2):91-106.

AUTORES / AUTHORS:  - Boggi U; Danesi R; Vistoli F; Del Chiaro M; Signori S; Marchetti P; Del Tacca M; Mosca F

INSTITUCIÓN / INSTITUTION:  - Division of General Surgery and Transplants, Department of Oncology, Transplants and Advanced Technologies in Medicine, University of Pisa, Pisa, Italy. uboggi@med.unipi.it

RESUMEN / SUMMARY:  - Interleukin-2 (IL-2) and its receptor (IL-2R) play a central role in T lymphocyte activation and immune response after transplantation. Research on the biology of IL-2R allowed the identification of key signal transduction pathways involved in the generation of proliferative and antiapoptotic signals in T cells. The alpha-chain of the IL-2R is a specific peptide against which monoclonal antibodies have been raised, with the aim of blunting the immune response by means of inhibiting proliferation and inducing apoptosis in primed lymphocytes. Indeed, basiliximab, one of such antibodies, has proved to be effective in reducing the episodes of acute rejection after kidney and pancreas transplantation. The use of basiliximab was associated with a significant reduction in the incidence of any treated rejection episodes after kidney transplantation in the two major randomised studies (placebo 52.2% vs basiliximab 34.2% at 6 months, European study; placebo 54.9% vs basiliximab 37.6% at 1 year, US trial). Basiliximab and equine antithymocyte globulin (ATG) administration resulted in a similar rate of biopsy-proven acute rejection at 6 months (19% for both) and at 12 months (19% and 20%, respectively). The use of basiliximab appears not to be associated with an increased incidence of adverse events as compared with placebo in immunosuppressive regimens, including calcineurin inhibitors, mycophenolate mofetil or azathioprine and corticosteroids, and its safety profile is superior to ATG. Moreover, a similar occurrence of infections is noted in selected studies (65.5% after basiliximab vs 65.7% of controls), including cytomegalovirus infection (17.3% vs 14.5%), and cytokine-release syndrome is not observed. Finally, economic analysis demonstrated lower costs of overall treatment in patients treated with basiliximab. Therefore, the use of basiliximab entails a very low risk, allows safe reduction of corticosteroid dosage and reduces the short- and mid-term rejection rates. However, the improvement in the long-term survival of kidney grafts in patients treated according to modern immunosuppressive protocols is still to be demonstrated. These conclusions are based on a systematic review of the scientific literature, indexed on Medline database, concerning the mechanism of action, therapeutic activity, safety and pharmacoeconomic evaluation of basiliximab in renal transplantation.  N. Ref:: 62

 

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[11]

TÍTULO / TITLE:  - Drug-eluting stents and glycoprotein IIb/IIIa inhibitors: combination therapy for the future.

REVISTA / JOURNAL:  - Am Heart J 2003 Oct;146(4 Suppl):S13-7.

      ●● Enlace al texto completo (gratuito o de pago) 1016/j.ahj.2003.09.004

AUTORES / AUTHORS:  - Leon MB; Bakhai A

RESUMEN / SUMMARY:  - BACKGROUND: Although coronary stenting has improved the results of coronary interventions compared to coronary angioplasty alone, in-stent restenosis remains a significant limitation of this procedure. Drug-eluting stents with or without glycoprotein IIb/IIIa inhibitor therapy represent an additional advance in the evolution of this strategy. METHODS: We review the currently available trials comparing studies of non-drug-eluting and drug-eluting stents using sirolimus and paclitaxel agents and their derivatives. RESULTS: Ten studies are available that compare drug-eluting to traditional non-drug-eluting stents. A variety of antiplatelet regimes have been used. The majority of these studies are in the process of being published. No head-to-head studies comparing different drug-eluting stents are available. CONCLUSIONS: Drug-eluting stents using sirolimus and paclitaxel in combination with enhanced antiplatelet strategies represent an important advantage over non-drug-eluting stents for the reduction of in-stent restenosis. The rate at which drug-eluting stents are adapted into widespread practice depends heavily on whether they are safe, efficacious, and cost-effective in various clinical settings.  N. Ref:: 28

 

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[12]

TÍTULO / TITLE:  - TOR inhibitors and cardiac allograft vasculopathy: is inhibition of intimal thickening an adequate surrogate of benefit?

REVISTA / JOURNAL:  - J Heart Lung Transplant 2003 May;22(5):501-4.

AUTORES / AUTHORS:  - Mehra MR; Uber PA

INSTITUCIÓN / INSTITUTION:  - Cardiomyopathy and Heart Transplantation Center, Ochsner Clinic Foundation, New Orleans, Louisiana 70121, USA. mmehra@ochsner.org  N. Ref:: 30

 

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[13]

TÍTULO / TITLE:  - FTY720: altered lymphocyte traffic results in allograft protection.

REVISTA / JOURNAL:  - Transplantation 2001 Sep 15;72(5):764-9.

AUTORES / AUTHORS:  - Brinkmann V; Pinschewer DD; Feng L; Chen S

INSTITUCIÓN / INSTITUTION:  - Novartis Pharma AG, Transplantation Research, WSJ-386.1.01, CH-4002 Basel, Switzerland.  N. Ref:: 52

 

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[14]

TÍTULO / TITLE:  - Basiliximab: a review of its use as induction therapy in renal transplantation.

REVISTA / JOURNAL:  - Drugs 2003;63(24):2803-35.

AUTORES / AUTHORS:  - Chapman TM; Keating GM

INSTITUCIÓN / INSTITUTION:  - Adis International Limited, Auckland, New Zealand. demail@adis.co.nz

RESUMEN / SUMMARY:  - Basiliximab (Simulect), a chimeric (human/murine) monoclonal antibody, is indicated for the prevention of acute organ rejection in adult and paediatric renal transplant recipients in combination with other immunosuppressive agents.Basiliximab significantly reduced acute rejection compared with placebo in renal transplant recipients receiving dual- (cyclosporin microemulsion and corticosteroids) or triple-immunotherapy (azathioprine- or mycophenolate mofetil-based); graft and patient survival rates at 12 months were similar. Significantly more basiliximab than placebo recipients were free from the combined endpoint of death, graft loss or acute rejection 3 years, but not 5 years, after transplantation.The incidence of adverse events was similar in basiliximab and placebo recipients, with no increase in the incidence of infection, including cytomegalovirus (CMV) infection. Malignancies or post-transplant lymphoproliferative disorders after treatment with basiliximab were rare, with a similar incidence to that seen with placebo at 12 months or 5 years post-transplantation. Rare cases of hypersensitivity reactions to basiliximab have been reported.The efficacy of basiliximab was similar to that of equine antithymocyte globulin (ATG) and daclizumab, and similar to or greater than that of muromonab CD3. Basiliximab was as effective as rabbit antithymocyte globulin (RATG) in patients at relatively low risk of acute rejection, but less effective in high-risk patients. Numerically or significantly fewer patients receiving basiliximab experienced adverse events considered to be related to the study drug than ATG or RATG recipients. The incidence of infection, including CMV infection, was similar with basiliximab and ATG or RATG.Basiliximab plus baseline immunosuppression resulted in no significant differences in acute rejection rates compared with baseline immunosuppression with or without ATG or antilymphocyte globulin in retrospective analyses conducted for small numbers of paediatric patients. Limited data from paediatric renal transplant recipients suggest a similar tolerability profile to that in adults. Basiliximab appears to allow the withdrawal of corticosteroids or the use of corticosteroid-free or calcineurin inhibitor-sparing regimens in renal transplant recipients.Basiliximab did not increase the overall costs of therapy in pharmacoeconomic studies.CONCLUSION: Basiliximab reduces acute rejection without increasing the incidence of adverse events, including infection and malignancy, in renal transplant recipients when combined with standard dual- or triple-immunotherapy. The overall incidence of death, graft loss or acute rejection was significantly reduced at 3 years; there was no significant difference for this endpoint 5 years after transplantation. Malignancy was not increased at 5 years. The overall efficacy, tolerability, ease of administration and cost effectiveness of basiliximab make it an attractive option for the prophylaxis of acute renal transplant rejection.  N. Ref:: 85

 

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[15]

- Castellano -

TÍTULO / TITLE:La enfermedad linfoproliferativa difusa postrasplante renal y su relacion con el virus Epstein-Barr. Experiencia de un centro. Diffuse lymphoproliferative disease after renal transplantation and its relation with Epstein-Barr virus. Experience at one center.

REVISTA / JOURNAL:  - Nefrologia. Acceso gratuito al texto completo.

      ●● Enlace a la Editora de la Revista http://www.aulamedica.es/nefrologia/ 

      ●● Cita: Nefrologia: <> 2002;22(5):463-9.

AUTORES / AUTHORS:  - Franco A; Jimenez L; Aranda I; Alvarez L; Gonzalez M; Rocamora N; Olivares J

INSTITUCIÓN / INSTITUTION:  - Servicio de Nefrologia Hospital General Alicante Maestro Alonso, 109 03010 Alicante. franco_ant@gva.es

RESUMEN / SUMMARY:  - Post-transplant lymphoproliferative disorders (PTLD) are a group of heterogeneous lymphoid proliferations in chronic immunosuppressed recipients which appear to be related to Epstein Barr Virus (EBV). Receptor EBV seronegativity, use of antilymphocyte antibodies and CMV disease have been identified as risk factors that may tigger development of PTLD. We have studied the incidence of PTLD and its relationship with EBV in 588 adult renal transplant recipients who were transplanted in our hospital from 1988 to 2001. We have also evaluated the diagnostic and therapeutic methods used, the risk factors and outcome of the patients who developed PTLD. We identified 8 recipients (4 males and 4 females), range from 18 to 67 years (mean age 45.6 years) with a median time between grafting and PTLD of 4.1 years (0.1-7 years), who developed PTLD (1.3%). Only 1 patient received OKT3 and had CMV disease, two of them (25%) had been treated with hight doses of prednisolone, another was EBV seronegative, but the rest of them (50%) had no risk factors. Two patients were diagnosed at autopsy, the diagnosis of 5 was based on the histology of biopsy and the last one by CT scans of chest-abdomen and cytology. The presence of EBV in the lymphoproliferative cells was assessed in 5 out of the 7 studied patients (71.4%). The outcome of our recipients was poor. Five out of 8 patients died shortly after diagnosis as a direct consecuence of PTLD and another of an infectious complication of the treatment (75%). The 2 patients alive started dialysis and 1 of them died 2 years later of a non-related cause. In conclusion, PTLD is a relatively frequent disease with a poor prognosis in renal transplant patients. It seems to have a close relationship with EBV and can develop in the absence of the classical risk factors.  N. Ref:: 18

 

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[16]

TÍTULO / TITLE:  - European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.10. Pregnancy in renal transplant recipients.

REVISTA / JOURNAL:  - Nephrol Dial Transplant. Acceso gratuito al texto completo a partir de los 2 años de la fecha de publicación.

      ●● Enlace a la Editora de la Revista http://ndt.oupjournals.org/ 

      ●● Cita: Nephrology Dialysis Transplantation: <> 2002;17 Suppl 4:50-5.

RESUMEN / SUMMARY:  - GUIDELINES: A. Renal transplantation restores fertility, and successful pregnancies have been reported in renal transplant women. In women with normal graft function, pregnancy usually has no adverse effect on graft function and survival. Therefore, women of childbearing age who consider pregnancy should receive complete information and support from the transplant team. B. Pregnancy could be considered safe about 2 years after transplantation in women with good renal function, without proteinuria, without arterial hypertension, with no evidence of ongoing rejection and with normal allograft ultrasound. C. Pregnancy after transplantation should be considered a high-risk pregnancy and should be monitored by both an obstetrician and the transplant physician. Pregnancy should be diagnosed as early as possible. The principal risks are infection, proteinuria, anaemia, arterial hypertension and acute rejection for the mother, and prematurity and low birth weight for the foetus. D. Pregnant women and transplanted patients are at increased risk of infections, especially bacterial urinary tract infections and acute pyelonephritis of the graft. Urine cultures should be performed monthly and all asymptomatic infections should be treated. Monitoring of viral infections is also recommended. (Evidence level B) E. Acute rejection episodes are uncommon but may occur after delivery. Therefore, immunosuppression should be re-adjusted immediately after delivery. F. Because pre-eclampsia develops in 30% of pregnant patients, especially those with prior arterial transplant hypertension, blood pressure, renal function, proteinuria and weight should be monitored every 2-4 weeks, with more attention during the third trimester. Anti-hypertensive agents should be changed to those tolerated during pregnancy. ACE inhibitors and angiotensin II receptor antagonists are absolutely contra-indicated. G. Immunosuppressive therapy based on cyclosporine or tacrolimus with or without steroids and azathioprine may be continued in renal transplant women during pregnancy. Other drugs, such as mycophenolate mofetil and sirolimus, are not recommended based on current information available. Because of drug transfer into maternal milk, breastfeeding is not recommended. H. Vaginal delivery is recommended, but caesarean section is required in at least 50% of cases. Delivery should occur in a specialized centre. In the puerperium, renal function, proteinuria, blood pressure, cyclosporine/tacrolimus blood levels and fluid balance should be closely monitored.

 

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[17]

TÍTULO / TITLE:  - Cryptococcus neoformans infection in organ transplant recipients: variables influencing clinical characteristics and outcome.

REVISTA / JOURNAL:  - Emerg Infect Dis. Acceso gratuito al texto completo.

      ●● Enlace a la Editora de la Revista http://www.cdc.gov/ 

      ●● Cita: Emerging Infectious Diseases: <> 2001 May-Jun;7(3):375-81.

AUTORES / AUTHORS:  - Husain S; Wagener MM; Singh N

INSTITUCIÓN / INSTITUTION:  - Veterans Affairs Medical Center and University of Pittsburgh, Thomas E. Starzl Transplantation Institute, Pittsburgh, Pennsylvania 15240, USA.

RESUMEN / SUMMARY:  - Unique clinical characteristics and other variables influencing the outcome of Cryptococcus neoformans infection in organ transplant recipients have not been well defined. From a review of published reports, we found that C. neoformans infection was documented in 2.8% of organ transplant recipients (overall death rate 42%). The type of primary immunosuppressive agent used in transplantation influenced the predominant clinical manifestation of cryptococcosis. Patients receiving tacrolimus were significantly less likely to have central nervous system involvement (78% versus 11%, p =0.001) and more likely to have skin, soft-tissue, and osteoarticular involvement (66% versus 21%, p = 0.006) than patients receiving nontacrolimus- based immunosuppression. Renal failure at admission was the only independently significant predictor of death in these patients (odds ratio 16.4, 95% CI 1.9-143, p = 0.004). Hypotheses based on these data may elucidate the pathogenesis and may ultimately guide the management of C. neoformans infection in organ transplant recipients.  N. Ref:: 74

 

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[18]

TÍTULO / TITLE:  - Mechanisms and consequences of arterial hypertension after renal transplantation.

REVISTA / JOURNAL:  - Transplantation 2001 Sep 27;72(6 Suppl):S9-12.

AUTORES / AUTHORS:  - Koomans HA; Ligtenberg G

INSTITUCIÓN / INSTITUTION:  - Department of Nephrology and Hypertension, University Hospital Utrecht, The Netherlands. h.a.koomans@digd.azu.nl

RESUMEN / SUMMARY:  - The high incidence of hypertension after renal transplantation contributes to the risk of cardiovascular morbidity and mortality in renal transplant recipients. Although cyclosporine has been influential in the improvement of transplant outcome, it has emerged as a major cause of hypertension after organ transplantation. The underlying pathophysiological mechanisms of cyclosporine-induced hypertension include enhanced sympathetic nervous system activity, renal vasoconstriction, and sodium/water retention. Hypertension is also significantly associated with reduced graft survival and thereby requires aggressive treatment intervention. Calcium channel blockers may offer some advantages over angiotensin-converting enzyme inhibitors for the treatment of hypertension in stable renal transplant recipients. Nevertheless, selection of the most appropriate antihypertensive agent should take into account the possibility of pharmacokinetic interactions with immunosuppressive agents. There is evidence to suggest that the use of tacrolimus-based immunosuppression induces less hypertension compared with cyclosporine. Not only do patients receiving tacrolimus tend to require less antihypertensive therapy, but converting patients from cyclosporine to tacrolimus has been shown to result in significant reductions in blood pressure. Thus, tacrolimus may be associated with an improved cardiovascular risk profile in renal transplant recipients.  N. Ref:: 26

 

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[19]

TÍTULO / TITLE:  - Controlling the incidence of infection and malignancy by modifying immunosuppression.

REVISTA / JOURNAL:  - Transplantation 2001 Dec 27;72(12 Suppl):S89-93.

AUTORES / AUTHORS:  - Soulillou JP; Giral M

RESUMEN / SUMMARY:  - Long-term outcomes in renal transplantation have improved over the years but are still a matter of concern. Because patients typically require lifelong immunosuppression, the risks of cancer and infection associated with immunosuppressive agents continue to demand attention. Physicians strive endlessly to find the right balance between the level of immunosuppression required to prevent rejection and the level that will minimize dose-dependent side effects. Data presented in this paper suggest that some renal transplant recipients might have more than necessary immunosuppression during maintenance therapy and that reducing the immunosuppressant dose can decrease cancer incidence, without worsening long-term patient or allograft survival. Additionally, data were examined suggesting that immunosuppressive agents might be associated with different risks for cancer, specifically, the potential advantage of reduced cancer risk for sirolimus and sirolimus derivatives in comparison with standard immunosuppressive agents. Although promising, these preliminary results are from preclinical studies, and further study is warranted.  N. Ref:: 42

 

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[20]

TÍTULO / TITLE:  - Effect of immunosuppressive treatment protocol on malignancy development in renal transplant patients.

REVISTA / JOURNAL:  - Transplant Proc 2002 Sep;34(6):2133-5.

AUTORES / AUTHORS:  - Haberal M; Moray G; Karakayali H; Emiroglu R; Basaran O; Sevmis S; Demirhan B

INSTITUCIÓN / INSTITUTION:  - Baskent University Faculty of Medicine, Ankara, Turkey. melekk@baskent-ank.edu.tr

 

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[21]

TÍTULO / TITLE:  - Effective prophylactic protocol in delayed hypersensitivity to contrast media: report of a case involving lymphocyte transformation studies with different compounds.

REVISTA / JOURNAL:  - Radiology. Acceso gratuito al texto completo a partir de los 2 años de la publicación;  - http://radiology.rsnajnls.org/ 

      ●● Cita: Radiology: <> 2002 Nov;225(2):466-70.

AUTORES / AUTHORS:  - Romano A; Artesani MC; Andriolo M; Viola M; Pettinato R; Vecchioli-Scaldazza A

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine and Geriatrics, Universita’ Cattolica del Sacro Cuore, Allergy Unit, Complesso Integrato Columbus, Via G. Moscati 31, 00168 Rome, Italy. columbus.allerg@linet.it

RESUMEN / SUMMARY:  - A patient with maculopapular reactions to iopamidol needed to undergo angiography for a cerebral arteriovenous malformation. In vivo and in vitro tests were performed with ionic and nonionic contrast media, including iopamidol and iobitridol. All results were positive, demonstrating delayed hypersensitivity. The patient received 6-alpha-methylprednisolone and cyclosporine 1 week before and 2 weeks after four angiograms were obtained with the use of iobitridol, which was well tolerated.

 

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[22]

TÍTULO / TITLE:  - Potential therapeutic interventions to avoid or treat chronic allograft dysfunction.

REVISTA / JOURNAL:  - Transplantation 2001 Jun 15;71(11 Suppl):SS52-7.

AUTORES / AUTHORS:  - Kahan BD

INSTITUCIÓN / INSTITUTION:  - University of Texas Medical School Houston, United States.

RESUMEN / SUMMARY:  - Despite the significant improvements that have occurred since the introduction of CsA, long-term renal allograft survival continues to be an area of concern. Management strategies that involve the use of sirolimus offer some promise. A number of observations suggest that sirolimus may have the ability to reduce the rates or slow the progression of chronic nephropathy. First, sirolimus has been shown to inhibit growth-factor-driven proliferation of endothelial and smooth muscle cells in vitro (55, 56). Sirolimus also disrupts signal transduction by a variety of other cytokines such as EGF and PDGE This is significant because cytokine- and growth-factor-stimulated proliferation of endothelial cells, smooth muscle cells, parenchymal cells, and fibroblasts appears to underlie the development of chronic nephropathy (see Fellstrom, this supplement). Second, sirolimus has been demonstrated in various animal models to inhibit the arterial intimal thickening that typically follows alloimmune or mechanical injury (56-60; see Morris, this supplement). This transplant vasculopathy is a prominent feature in chronic rejection of other organ transplants. Moreover, at least 1 published study has suggested that sirolimus may be able to stabilize and possibly reverse chronic graft vascular disease (61). However, the relative doses of sirolimus used in these animal studies have been higher than those used in humans, so the relationship of these effects to the clinical setting needs to be further studied to define the relevance of these findings. Third, sirolimus, used in combination with CsA, reduces the incidence of acute rejection episodes in humans, one of the most significant predictors of shortened renal allograft survival (62, 63). Thus, an effect of sirolimus to reduce acute rejection episodes or delay their onset is expected to reduce renal allograft loss. Furthermore, clinical trials suggest that sirolimus treatment may allow dose reductions of CsA or a delay in inception of CsA therapy, which might reduce the acute and chronic nephrotoxicity associated with CsA and other CNIs. Since nephrotoxicity may promote or aggravate renal injury and appears to be common in chronic nephropathy (see Fellstrom and Paul, this supplement), reduced exposure to CNIs may translate into reduced rates of chronic renal allograft dysfunction. There are no currently effective therapies for chronic nephropathy, which is a common cause of late renal allograft loss. Preliminary evidence suggests that sirolimus may eventually prove useful as prophylaxis of or treatment for chronic nephropathy. Thus, sirolimus has come to be regarded as the foundation for maintenance immunosuppressive regimens.  N. Ref:: 63

 

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[23]

TÍTULO / TITLE:  - Drug-eluting stents: potential applications for peripheral arterial occlusive disease.

REVISTA / JOURNAL:  - J Vasc Interv Radiol 2003 Mar;14(3):291-301.

AUTORES / AUTHORS:  - Duda SH; Poerner TC; Wiesinger B; Rundback JH; Tepe G; Wiskirchen J; Haase KK

INSTITUCIÓN / INSTITUTION:  - Department of Diagnostic Radiology, University of Tuebingen, Germany. stephan.duda@med.uni-tuebingen.de

RESUMEN / SUMMARY:  - Many different approaches have been evaluated to prevent restenosis in stents after vascular implantation. Currently, drug-eluting stents are extremely promising in suppressing neointimal hyperplasia. Various animal studies and randomized trials in humans have shown excellent results in terms of safety and efficacy during intermediate-term follow-up. This article will give an overview of experimental and clinical data of the different agents in published and ongoing trials.  N. Ref:: 87

 

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[24]

TÍTULO / TITLE:  - Engineered CD3 antibodies for immunosuppression.

REVISTA / JOURNAL:  - Clin Exp Immunol 2003 Sep;133(3):307-9.

AUTORES / AUTHORS:  - Renders L; Valerius T  N. Ref:: 30

 

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[25]

TÍTULO / TITLE:  - Risk factors for bronchiolitis obliterans: a systematic review of recent publications.

REVISTA / JOURNAL:  - J Heart Lung Transplant 2002 Feb;21(2):271-81.

AUTORES / AUTHORS:  - Sharples LD; McNeil K; Stewart S; Wallwork J

INSTITUCIÓN / INSTITUTION:  - Medical Research Council (MRC) Biostatistics Unit, University Forvie Site, Papworth Everard, Cambridge, United Kingdom. linda.sharples@mrc-bsu.cam.ac.uk

RESUMEN / SUMMARY:  - BACKGROUND: Obliterative bronchiolitis remains the major limitation to long-term survival after lung transplantation. A thorough understanding of the factors that confer high risk of developing obliterative bronchiolitis or its physiologic surrogate bronchiolitis obliterans syndrome is important to help define therapeutic strategies. METHODS: We performed a systematic review of studies published since the beginning of 1990. The review excluded non-human studies, publications before 1990, small (less than 25 patients) studies that were predominantly concerned with investigating the pathogenesis of obliterative bronchiolitis, studies solely concerned with diagnosis or treatment of obliterative bronchiolitis, and overlapping studies from the same center. Onset of bronchiolitis obliterans syndrome or obliterative bronchiolitis was the outcome of interest. RESULTS: Acute rejection plays an important role in obliterative bronchiolitis and bronchiolitis obliterans syndrome onset, and late rejection is a significant risk factor. Lymphocytic bronchitis/bronchiolitis is also a risk factor, with some evidence that late onset is associated with greater risk. The effects of cytomegalovirus, other infectious organisms, and human leukocyte antigen matching are less clear and require further confirmation. There is little evidence that recipient and donor characteristics play a major role. CONCLUSIONS: This systematic review supports the view that obliterative bronchiolitis arises from alloimmunologic injury marked by clinically apparent acute rejection episodes and that inflammatory conditions, including viral infections or ischemic injury, may also play a role. Implications for therapy are discussed.  N. Ref:: 28

 

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[26]

TÍTULO / TITLE:  - Use of nonsteroidal topical immunomodulators for the treatment of atopic dermatitis in the pediatric population.

REVISTA / JOURNAL:  - J Pediatr 2001 Feb;138(2):163-8.

AUTORES / AUTHORS:  - Paller AS

INSTITUCIÓN / INSTITUTION:  - Department of Pediatrics, Children’s Memorial Hospital, Northwestern University Medical School, Chicago, Illinois, USA.  N. Ref:: 39

 

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[27]

TÍTULO / TITLE:  - The porcine coronary model of in-stent restenosis: current status in the era of drug-eluting stents.

REVISTA / JOURNAL:  - Catheter Cardiovasc Interv 2003 Dec;60(4):515-23.

      ●● Enlace al texto completo (gratuito o de pago) 1002/ccd.10705