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Revisiones-Clínica-Diagnóstico *** Reviews-Clinical-Diagnostics

 

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:  - Preliminary guidelines for diagnosing and treating tuberculosis in patients with rheumatoid arthritis in immunosuppressive trials or being treated with biological agents.

REVISTA / JOURNAL:  - Ann Rheum Dis 2002 Nov;61 Suppl 2:ii62-3.

AUTORES / AUTHORS:  - Furst DE; Cush J; Kaufmann S; Siegel J; Kurth R

INSTITUCIÓN / INSTITUTION:  - UCLA Medical School, Los Angeles, USA Presbyterian Hospital, Dallas, USA.

 

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[2]

TÍTULO / TITLE:  - Overcoming restenosis with sirolimus: from alphabet soup to clinical reality.

REVISTA / JOURNAL:  - Lancet 2002 Feb 16;359(9306):619-22.

AUTORES / AUTHORS:  - Poon M; Badimon JJ; Fuster V

INSTITUCIÓN / INSTITUTION:  - Mount Sinai School of Medicine, 1 Gustav L Levy Place, Box 1030, New York, NY 10029, USA.  N. Ref:: 34

 

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[3]

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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[4]

TÍTULO / TITLE:  - Drug immunosuppression therapy for adult heart transplantation. Part 2: clinical applications and results.

REVISTA / JOURNAL:  - Ann Thorac Surg 2004 Jan;77(1):363-71.

AUTORES / AUTHORS:  - Mueller XM

INSTITUCIÓN / INSTITUTION:  - Department of Cardiovascular Surgery, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada. xavier.mueller@usherbrooke.ca

RESUMEN / SUMMARY:  - This review describes the clinical application of classical immunosuppressive drugs as well as that of more recent drugs. All current immunosuppressive drugs target T-cell activation, and cytokine production and clonal expansion, or both. Immunosuppressive protocols can be broadly divided into induction therapy, maintenance immunosuppression, and treatment of acute rejection episodes.  N. Ref:: 82

 

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[5]

TÍTULO / TITLE:  - Renal transplantation: can we reduce calcineurin inhibitor/stop steroids? Evidence based on protocol biopsy findings.

REVISTA / JOURNAL:  - J Am Soc Nephrol. Acceso gratuito al texto completo a partir de 1 año de la fecha de publicación.

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

      ●● Cita: Journal of the American Society of Nephrology: <> 2003 Mar;14(3):755-66.

AUTORES / AUTHORS:  - Gotti E; Perico N; Perna A; Gaspari F; Cattaneo D; Caruso R; Ferrari S; Stucchi N; Marchetti G; Abbate M; Remuzzi G

INSTITUCIÓN / INSTITUTION:  - Department of Medicine and Transplantation, Ospedali Riuniti di Bergamo, Mario Negri Institute for Pharmacological Research, Italy.

RESUMEN / SUMMARY:  - How to combine antirejection drugs and which is the optimal dose of steroids and calcineurin inhibitors beyond the first year after kidney transplantation to maintain adequate immunosuppression without major side effects are far from clear. Kidney transplant patients on steroid, cyclosporine (CsA), and azathioprine were randomized to per-protocol biopsy (n = 30) or no-biopsy (n = 29) 1 to 2 yr posttransplant. Steroid or CsA were discontinued or reduced on the basis of biopsy to establish effects on drug-related complications, acute rejection, and graft function over 3 yr of follow-up. Serum creatinine, GFR (plasma clearance of iohexol), RPF (renal clearance of p-aminohippurate), CsA pharmacokinetics, and adverse events were monitored yearly. At the end, patients underwent a second biopsy. Per-protocol biopsy histology revealed no lesions (n = 5, steroid withdrawal), CsA nephropathy (n = 13, CsA discontinuation/reduction), or chronic rejection (n = 12, standard therapy). Reducing the drug regimen led to overall fewer side effects related to immunosuppression as compared with standard therapy or no-biopsy. Steroids were safely stopped with no acute rejection or graft loss. Complete CsA discontinuation was associated with acute rejection in the first four patients. Lowering CsA to low target CsA trough (30 to 70 ng/ml) never led to acute rejection or major renal function deterioration. Biopsy patients on conventional regimen had no acute rejection, one graft loss, no significant change in GFR, and significant RPF decline. No-biopsy controls: no acute rejection, one graft loss, significant decline of GFR and RPF. By serial biopsy analysis, severe lesions did not develop in patients with steroid discontinuation in contrast to patients on standard therapy over follow-up. CsA reduction did not adversely affect histology. Per-protocol biopsy more than 1 yr after kidney transplantation is a safe procedure to guide change of drug regimen and to lower the risk of major side effects.

 

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[6]

TÍTULO / TITLE:  - Drug immunosuppression therapy for adult heart transplantation. Part 1: immune response to allograft and mechanism of action of immunosuppressants.

REVISTA / JOURNAL:  - Ann Thorac Surg 2004 Jan;77(1):354-62.

AUTORES / AUTHORS:  - Mueller XM

INSTITUCIÓN / INSTITUTION:  - Department of Cardiovascular Surgery, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada. xavier.mueller@usherbrooke.ca

RESUMEN / SUMMARY:  - In the early days of transplantation, immunosuppression therapy was rather broad and nonspecific, mainly using high-dose corticosteroids and azathioprine. Thereafter we progressively narrowed the target of immunosuppressive strategy starting with polyclonal antibodies. The introduction of cyclosporine, OKT3, and tacrolimus further narrowed the target on the T-cell pathways. More recently mycophenolate mofetil progressively took the place of azathioprine with its higher lymphocyte specificity and sirolimus and interleukin-2 receptor antibodies were introduced. In this field in constant movement the aim is to find a drug or a regimen that provides optimal immunosuppression therapy with minimal side effects, in other words to find the right balance between overimmunosuppression and underimmunosuppression therapy. This review is divided into two parts. The first part will provide a basic understanding of the immunologic response to allograft and explain how conventional and recently introduced immunosuppressive agents work. The second part will describe the clinical application of immunosuppressive drugs to provide practical information for those in charge of heart transplant recipients.  N. Ref:: 68

 

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[7]

TÍTULO / TITLE:  - Cyclosporin trough levels: is monitoring necessary during short-term treatment in psoriasis? A systematic review and clinical data on trough levels.

REVISTA / JOURNAL:  - Br J Dermatol 2002 Jul;147(1):122-9.

AUTORES / AUTHORS:  - Heydendael VM; Spuls PI; Ten Berge IJ; Opmeer BC; Bos JD; de Rie MA

INSTITUCIÓN / INSTITUTION:  - Department of Dermatology, Academic Medical Center, University of Amsterdam, PO Box 22660, the Netherlands.

RESUMEN / SUMMARY:  - BACKGROUND: Cyclosporin is an effective treatment for severe plaque psoriasis. Unfortunately, its use may be limited by time- and dose-related nephrotoxicity. Serum trough levels may be useful for monitoring the risk of nephrotoxicity. OBJECTIVES: To determine whether monitoring of trough levels is necessary in psoriasis patients undergoing short-term treatment with cyclosporin. METHODS: A computerized and manual literature search identified studies on adults with plaque-type psoriasis treated with cyclosporin < or = 5 mg kg-1 daily, in which trough levels were measured in whole blood. Number of patients, treatment duration, formulation and dosage, renal function tests and trough levels were extracted. The association between renal function and trough levels was investigated. Additionally, in a randomized controlled trial on cyclosporin vs. methotrexate in moderate to severe psoriasis, cyclosporin trough levels were measured frequently in 20 patients during 12 weeks of treatment. The Pearson correlation coefficient between serum creatinine and cyclosporin trough levels was calculated. RESULTS: Fifty-six articles were found concerning cyclosporin trough level measurements in psoriasis patients, of which eight were analysed. Many studies were excluded due to inappropriate cyclosporin dosages used. As data were heterogeneous and lacked various key parameters, a correlation study and a meta-analysis could not be performed. Instead, a quantitative description of the literature was given. No high mean trough levels or elevations of serum creatinine were described. In our clinical study, all the mean trough levels in 17 patients treated with cyclosporin 3 mg kg-1 daily were within the therapeutic range (< 200 ng mL-1). Elevated trough levels were found in two of three patients treated with cyclosporin 3-5 mg kg-1 daily. No signs of renal dysfunction were seen. CONCLUSIONS: The literature does not provide a definitive answer on whether monitoring cyclosporin trough levels in patients with psoriasis should be standard practice. Our own data show no need for cyclosporin trough level monitoring during short-term treatment with cyclosporin 3 mg kg-1 daily. However, when cyclosporin doses are > 3 mg kg-1 daily, monitoring may be indicated.  N. Ref:: 32

 

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[8]

TÍTULO / TITLE:  - Subcutaneous panniculitic T-cell lymphoma in children: response to combination therapy with cyclosporine and chemotherapy.

REVISTA / JOURNAL:  - J Am Acad Dermatol 2004 Feb;50(2 Suppl):S18-22.

      ●● Enlace al texto completo (gratuito o de pago) 1016/S0190

AUTORES / AUTHORS:  - Shani-Adir A; Lucky AW; Prendiville J; Murphy S; Passo M; Huang FS; Paller AS

INSTITUCIÓN / INSTITUTION:  - Division of Dermatology, Children’s Memorial Hospital, 2300 Children’s Plaza, Chicago, IL 60614, USA.

RESUMEN / SUMMARY:  - We describe 2 adolescent boys with facial swelling and/or subcutaneous nodules and fever. Extensive evaluation, including several biopsy specimens, led to a diagnosis of subcutaneous panniculitic T-cell lymphoma, an entity rarely seen in children. Both patients were treated with oral cyclosporine in an effort to suppress the cytokine release from T-cells that has been thought to induce the hemophagocytic syndrome. The patients responded dramatically to cyclosporine treatment with defervescence of the fever and reduction in number and size of the subcutaneous nodules. Subsequent therapy with multidrug chemotherapy achieved complete remission in the first patient. This report suggests the value of cyclosporine as a first-line agent coupled with chemotherapy in the treatment of patients with subcutaneous panniculitic T-cell lymphoma. A clinicopathologic review of 8 described pediatric cases of subcutaneous panniculitic T-cell lymphoma is also presented.  N. Ref:: 15

 

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[9]

TÍTULO / TITLE:  - Patient management by Neoral C(2) monitoring: an international consensus statement.

REVISTA / JOURNAL:  - Transplantation 2002 May 15;73(9 Suppl):S12-8.

AUTORES / AUTHORS:  - Levy G; Thervet E; Lake J; Uchida K

INSTITUCIÓN / INSTITUTION:  - Multiorgan Transplant Program, Toronto General Hospital, 621 University Avenue, 10NU-116, Toronto, Ontario M5G 2C4, Canada.  N. Ref:: 36

 

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[10]

TÍTULO / TITLE:  - Immunoablation followed or not by hematopoietic stem cells as an intense therapy for severe autoimmune diseases. New perspectives, new problems.

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

      ●● Enlace a la Editora de la Revista http://db.doyma.es/ 

      ●● Cita: Haematologica: <> 2001 Apr;86(4):337-45.

AUTORES / AUTHORS:  - Marmont AM  N. Ref:: 127

 

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[11]

TÍTULO / TITLE:  - Inflammatory myopathies: clinical, diagnostic and therapeutic aspects.

REVISTA / JOURNAL:  - Muscle Nerve 2003 Apr;27(4):407-25.

      ●● Enlace al texto completo (gratuito o de pago) 1002/mus.10313

AUTORES / AUTHORS:  - Mastaglia FL; Garlepp MJ; Phillips BA; Zilko PJ

INSTITUCIÓN / INSTITUTION:  - Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Queen Elizabeth II Medical Centre, Nedlands, Australia. flmast@cyllene.uwa.edu.au

RESUMEN / SUMMARY:  - The three major forms of immune-mediated inflammatory myopathy are dermatomyositis (DM), polymyositis (PM), and inclusion-body myositis (IBM). They each have distinctive clinical and histopathologic features that allow the clinician to reach a specific diagnosis in most cases. Magnetic resonance imaging is sometimes helpful, particularly if the diagnosis of IBM is suspected but has not been formally evaluated. Myositis-specific antibodies are not helpful diagnostically but may be of prognostic value; most antibodies have low sensitivity. Muscle biopsy is mandatory to confirm the diagnosis of an inflammatory myopathy and to allow unusual varieties such as eosinophilic, granulomatous, and parasitic myositis, and macrophagic myofasciitis, to be recognized. The treatment of the inflammatory myopathies remains largely empirical and relies upon the use of corticosteroids, immunosuppressive agents, and intravenous immunoglobulin, all of which have nonselective effects on the immune system. Further controlled clinical trials are required to evaluate the relative efficacy of the available therapeutic modalities particularly in combinations, and of newer immunosuppressive agents (mycophenolate mofetil and tacrolimus) and cytokine-based therapies for the treatment of resistant cases of DM, PM, and IBM. Improved understanding of the molecular mechanisms of muscle injury in the inflammatory myopathies should lead to the development of more specific forms of immunotherapy for these conditions.  N. Ref:: 256

 

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[12]

TÍTULO / TITLE:  - How should the immunosuppressive regimen be managed in patients with established chronic allograft failure?

REVISTA / JOURNAL:  - Kidney Int Suppl 2002 May;(80):68-72.

AUTORES / AUTHORS:  - Danovitch GM

INSTITUCIÓN / INSTITUTION:  - Division of Nephrology, UCLA School of Medicine, USA. gdanovitch@mednet.ucla.edu  N. Ref:: 25

 

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[13]

TÍTULO / TITLE:  - Steroid-resistant kidney transplant rejection: diagnosis and treatment.

REVISTA / JOURNAL:  - J Am Soc Nephrol. Acceso gratuito al texto completo a partir de 1 año de la fecha de publicación.

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

      ●● Cita: Journal of the American Society of Nephrology: <> 2001 Feb;12 Suppl 17:S48-52.

AUTORES / AUTHORS:  - Bock HA

INSTITUCIÓN / INSTITUTION:  - Division of Nephrology, Kantonsspital, Aarau, Switzerland. bock@ksa.ch

RESUMEN / SUMMARY:  - Decreases in transplant function may be attributable to a variety of conditions, including prerenal and postrenal failure, cyclosporin A (CsA) toxicity, polyoma nephritis, recurrent glomerulonephritis, and rejection. The diagnosis of rejection should therefore be made on the basis of a transplant biopsy of adequate size, before the initiation of any therapy. Pulse steroid treatment (three to five 0.25- to 1.0-g pulses of methylprednisolone, administered intravenously) is the usual first-line therapy and has a 60 to 70% success rate, although orally administered prednisone (0.25 g) may be just as efficacious. Even if reverted, any rejection should trigger an at least temporary increase in basal immunosuppression, consisting of an increase in CsA or tacrolimus target levels, the addition of steroids or an increase in their dosage, the addition of mycophenolate mofetil, or a switch from CsA to tacrolimus. The addition of rapamycin or its RAD derivative may fulfill the same purpose. Steroid resistance should not be assumed before the fifth day of pulse steroid treatment, although histologic features of vascular rejection may indicate the need for more aggressive treatment earlier. Steroid-resistant rejection is traditionally treated with poly- or monoclonal antilymphocytic antibodies, with success rates of 60 to 70%. Their potential benefit must be carefully balanced against the risks of infection and lymphoma. More recently, mycophenolate mofetil has been successfully used to treat steroid-resistant rejection, but only of the interstitial (cellular) type. Switching from CsA to tacrolimus for treating recurrent or antibody-resistant rejection is successful in approximately 60% of cases. Plasmapheresis and intravenously administered Ig have been used in some desperate cases, with surprising success. Because none of the available drugs has a significantly better profile of therapeutic versus adverse effects, the possible benefits of continued rejection therapy must be continuously balanced with the potential for serious, sometimes fatal, side effects.  N. Ref:: 35

 

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[14]

TÍTULO / TITLE:  - Pharmacokinetic, pharmacodynamic, and outcome investigations as the basis for mycophenolic acid therapeutic drug monitoring in renal and heart transplant patients.

REVISTA / JOURNAL:  - Clin Biochem 2001 Feb;34(1):17-22.

AUTORES / AUTHORS:  - Shaw LM; Korecka M; DeNofrio D; Brayman KL

INSTITUCIÓN / INSTITUTION:  - Departments of Pathology & Laboratory Medicine and Surgery, University of Pennsylvania Medical Center, Philadelphia, PA, USA. shawlmj@mail.med.upenn.edu

RESUMEN / SUMMARY:  - Mycophenolate mofetil is widely used in combination with either cyclosporine or tacrolimus for rejection prophylaxis in renal and heart transplant patients. Although not monitored routinely nearly to the degree that other agents such as cyclosporine or tacrolimus, there is an expanding body of experimental evidence for the utility of monitoring mycophenolic acid, the primary active metabolite of mycophenolate mofetil, plasma concentration as an index of risk for the development of acute rejection. The following are important experimentally-based reasons for recommending the incorporation of target therapeutic concentration monitoring of mycophenolic acid: (1) the MPA dose-interval area-under-the-concentration-time curve, and less precisely, MPA predose concentrations predict the risk for development of acute rejection; (2) the strong correlation between mycophenolic acid plasma concentrations and expression of important cell surface activation antigens, whole blood pharmacodynamic assays of lymphocyte proliferation and median graft rejection scores in a heart transplant animal model; (3) the greater than 10-fold interindividual variation of MPA area under the concentration time curve values in heart and renal transplant patients receiving a fixed dose of the parent drug; (4) drug-drug interactions involving other immunosuppressives are such that when switching from one to another (eg, from cyclosporine to tacrolimus or vice-versa) substantial changes in MPA concentrations can occur in patients receiving a fixed dose of the parent drug; (5) significant effects of liver and kidney diseases on the steady-state total and free mycophenolic acid area under the concentration time curve values; (6) the need to closely monitor mycophenolic acid when a major change in immunosuppression is planned such as steroid withdrawal. Current investigations are focused on determination of the most optimal sampling time and for mycophenolic acid target therapeutic concentration monitoring. Further investigations are needed to evaluate the pharmacologic activity of the newly described acyl glucuronide metabolite of mycophenolic acid which has been shown to inhibit, in vitro, inosine monophosphate dehydrogenase.  N. Ref:: 37

 

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[15]

TÍTULO / TITLE:  - Clinical validation studies of Neoral C(2) monitoring: a review.

REVISTA / JOURNAL:  - Transplantation 2002 May 15;73(9 Suppl):S3-11.

AUTORES / AUTHORS:  - Nashan B; Cole E; Levy G; Thervet E

INSTITUCIÓN / INSTITUTION:  - Klinik fur Viszeral und Transplantationschirurgie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.  N. Ref:: 34

 

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[16]

TÍTULO / TITLE:  - European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.2.1 Differential diagnosis of chronic graft dysfunction.

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 4:4-8.

RESUMEN / SUMMARY:  - GUIDELINES: A. Any significant deterioration in graft function should be investigated using the appropriate diagnostic tools and, if possible, therapeutic interventions should be initiated. The usual causes of a decline in glomerular filtration rate after the first year include transplant-specific causes such as chronic allograft nephropathy, acute rejection episodes, chronic calcineurin inhibitor nephrotoxicity, transplant renal artery stenosis and ureteric obstruction, as well as immunodeficiency-related causes and non-transplant-related causes, such as recurrent or de novo renal diseases and bacterial infections. B. Any new onset and persistent proteinuria of >0.5 g/24 h should be investigated and therapeutic interventions should be initiated. The usual causes include chronic allograft nephropathy and transplant glomerulopathy, and recurrent or de novo glomerulonephritis.

 

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[17]

TÍTULO / TITLE:  - Treatment responses of childhood aplastic anaemia with chromosomal aberrations at diagnosis.

REVISTA / JOURNAL:  - Br J Haematol 2002 Jul;118(1):313-9.

AUTORES / AUTHORS:  - Ohga S; Ohara A; Hibi S; Kojima S; Bessho F; Tsuchiya S; Ohshima Y; Yoshida N; Kashii Y; Nishimura S; Kawakami K; Nishikawa K; Tsukimoto I

INSTITUCIÓN / INSTITUTION:  - Aplastic Anaemia Committee of the Japanese Society of Paediatric Haematology, Tokyo, Japan. ohgas@pediatr.med.kyushu-u.ac.jp

RESUMEN / SUMMARY:  - The clinical outcome of childhood aplastic anaemia (AA) with aberrant cytogenetic clones at diagnosis was surveyed. Among 198 children with newly diagnosed AA registered with the AA Committee of the Japanese Society of Paediatric Hematology between 1994 and 1998, cytogenetic studies of bone marrow (BM) cells were completed in 159 patients. Apart from one Robertsonian translocation, seven patients (4.4%) showed clonal chromosomal abnormalities in hypoplastic BM without myelodysplastic features. The patients included six girls and one boy with a median age of 11 years (range 5-14 years). Six patients had del(6), del(5), del(13), del(20), or -7, and one showed add(9). Four patients responded to the first immunosuppressive therapy (IST: cyclosporin A plus anti-thymocyte globulin) and one obtained a spontaneous remission. Cytogenetic abnormalities remained in two patients with an IST response. On the other hand, two patients showed no IST response. One did not respond to repeat IST and died of acute graft-versus-host disease after an unrelated-BM transplant. Another obtained a complete response after a successful BM transplant. No haematological findings at diagnosis predicted the treatment response. No significant morphological changes developed during the course of the illness. A literature review revealed that half of 24 AA patients with chromosomal abnormalities responded to the first IST, and that +6 was the sole predictable marker for IST unresponsiveness. These results suggest that IST can be applied as the initial therapy for AA with cytogenetic abnormalities in the absence of completely matched donors.  N. Ref:: 32

 

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[18]

TÍTULO / TITLE:  - International Federation of Clinical Chemistry/International Association of Therapeutic Drug Monitoring and Clinical Toxicology working group on immunosuppressive drug monitoring.

REVISTA / JOURNAL:  - Ther Drug Monit 2002 Feb;24(1):59-67.

AUTORES / AUTHORS:  - Holt DW; Armstrong VW; Griesmacher A; Morris RG; Napoli KL; Shaw LM

INSTITUCIÓN / INSTITUTION:  - Analytical Unit, St George’s Hospital Medical School, London, UK. d.holt@sghms.ac.uk

RESUMEN / SUMMARY:  - Issues surrounding the measurement and interpretation of immunosuppressive drug concentrations have been summarized in a number of consensus documents. The Scientific Division of the International Federation of Clinical Chemistry has formed a working group in collaboration with the International Association of Therapeutic Drug Monitoring and Clinical Toxicology. This paper sets out the goals of the working group in light of the developments that have occurred in the field of immunosuppressive drug monitoring since the publication of the last consensus documents.

 

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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:  - Guidelines for the diagnosis and management of acquired aplastic anaemia.

REVISTA / JOURNAL:  - Br J Haematol 2003 Dec;123(5):782-801.

AUTORES / AUTHORS:  - Marsh JC; Ball SE; Darbyshire P; Gordon-Smith EC; Keidan AJ; Martin A; McCann SR; Mercieca J; Oscier D; Roques AW; Yin JA

INSTITUCIÓN / INSTITUTION:  - St. George’s Hospital Medical School, London, UK. janice@bshhya.demon.co.uk

 

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[21]

TÍTULO / TITLE:  - A retrospective review of sirolimus (Rapamune) therapy in orthotopic liver transplant recipients diagnosed with chronic rejection.

REVISTA / JOURNAL:  - Liver Transpl 2003 May;9(5):477-83.

      ●● Enlace al texto completo (gratuito o de pago) 1053/jlts.2003.50119

AUTORES / AUTHORS:  - Neff GW; Montalbano M; Slapak-Green G; Berney T; Bejarano PA; Joshi A; Icardi M; Nery J; Seigo N; Levi D; Weppler D; Pappas P; Ruiz J; Schiff ER; Tzakis AG

INSTITUCIÓN / INSTITUTION:  - University of Miami, Department of Medicine, Miami, FL 33136, USA. gneff@med.miami.edu

RESUMEN / SUMMARY:  - Treatment options are limited for orthotopic liver transplant (OLT) recipients suffering from chronic rejection (CR). We performed a retrospective review of OLT recipients diagnosed with CR and treated with sirolimus. The medical records of all OLT recipients treated with sirolimus between October, 1998 and October, 2000 were retrospectively reviewed. The diagnosis of CR was made by both clinical and histologic criteria: bile duct to hepatic artery ratio less than 0.7, histologic activity index, hepatic arterial wall thickening, and chronic elevation of liver chemistries. Two groups were defined in regard to sirolimus response: sirolimus responders (SR) and sirolimus nonresponders (SNR). Response to treatment was granted only when patients were found to have resolution of abnormal liver transaminases and an improvement in hepatic artery to bile duct ratio. Serum collections for liver chemistries were collected on days 1, 30, 60, and 90. Liver biopsies were reviewed in blinded fashion from day 1 and at least 180 days on therapy by double-blinded pathologists. Sirolimus-related complications were recorded and include drug toxicity, anemia with and without treatment, hospitalizations, infections, immunosuppression complications, lipid profile disorders, edema, muscle aches, and gastrointestinal complaints. Twenty-one patients were diagnosed with CR. The SR group included 13 of 21, and 8 of 21 were in the SNR group. Anemia was diagnosed in 12 of 21 patients: SR, 7 of 13; SNR, 5 of 8; with 5 patients requiring red blood cell transfusions (2 SR, 3 SNR). Recombinant erythropoietin was started in 5 of 21 patients. Sirolimus serum levels were found to be greater than 20 ng/dL in 12 patients. Sirolimus was discontinued in 9 patients,

 

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[22]

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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[23]

TÍTULO / TITLE:  - Persistent remission after immunosuppressive therapy of hairy cell leukemia mimicking aplastic anemia: two case reports.

REVISTA / JOURNAL:  - Int J Hematol 2003 May;77(4):391-4.

AUTORES / AUTHORS:  - Sugimori C; Kaito K; Nakao S

INSTITUCIÓN / INSTITUTION:  - Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.

RESUMEN / SUMMARY:  - Some patients with hairy cell leukemia (HCL) manifest pancytopenia and bone marrow hypoplasia without an apparent increase in atypical cells, so their disease resembles severe aplastic anemia at onset. We treated 2 HCL patients, who were initially diagnosed with aplastic anemia, with antithymocyte globulin (ATG) in combination with cyclosporine or antilymphocyte globulin (ALG). Both patients obtained partial remission in response to the immunosuppressive therapy and did not need transfusion treatment for more than 3 years. Sustained improvement of hematopoiesis in such B-cell malignancies after ATG/ ALG therapy suggests that the mechanisms underlying successful immunosuppressive therapy for aplastic anemia may involve B-cell suppression, inhibiting hematopoietic stem cells.  N. Ref:: 18

 

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[24]

TÍTULO / TITLE:  - Histopathological study of intrahepatic islets transplanted in the nonhuman primate model using edmonton protocol immunosuppression.

REVISTA / JOURNAL:  - J Clin Endocrinol Metab. Acceso gratuito al texto completo a partir de 1 año de la fecha de publicación.

      ●● Enlace a la Editora de la Revista http://jcem.endojournals.org/ 

      ●● Cita: J. of Clin Endocrinol & Metab: <> 2002 Dec;87(12):5424-9.

AUTORES / AUTHORS:  - Hirshberg B; Mog S; Patterson N; Leconte J; Harlan DM

INSTITUCIÓN / INSTITUTION:  - Transplantation and Autoimmunity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.

RESUMEN / SUMMARY:  - While islet cell transplantation is a promising way to restore insulin independence to patients with type I diabetes mellitus, a detailed histological analysis of the transplanted, intraportal islets has not yet been reported. Rhesus macaques underwent total pancreatectomy, then had allogeneic isolated islets infused into their portal vein, followed by daclizumab, tacrolimus, and sirolimus to prevent islet rejection. Islets were evenly distributed among the liver lobes. Liver sections from a primate given allogeneic islets 5 d earlier did not display any islet capillary formation, whereas intrahepatic islets transplanted 30 and 90 d before euthanasia showed an abundant capillary supply. Localized hepatocellular glycogenosis was observed surrounding the islets in a primate with functioning islets 7 months post transplant. Liver sections from a primate that rejected islets transplanted 2 months prior displayed only islet remnants with prominent local lymphohistiocytic inflammation and an occasional capillary. We conclude that islets develop an abundant vascular supply within 30 d following transplant and because capillaries persist even following rejection, that the vascular cells are likely from the recipient. While transplanted islets were not vascularized early post transplant, the primates remained insulin independent. The long-term consequence of islets in the liver, marked by the glycogenosis, remains unknown and warrants further study.

 

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[25]

TÍTULO / TITLE:  - Resolution of oral non-Hodgkin’s lymphoma by reduction of immunosuppressive therapy in a renal allograft recipient: a case report and review of the literature.

REVISTA / JOURNAL:  - Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002 Dec;94(6):697-701.

      ●● Enlace al texto completo (gratuito o de pago) 1067/moe.2002.126889

AUTORES / AUTHORS:  - Keogh PV; Fisher V; Flint SR

INSTITUCIÓN / INSTITUTION:  - Department of Oral Surgery, Oral Medicine and Oral Pathology, Dublin Dental School and Hospital, Trinity College, Ireland. pakeogh@dental.tcd.ie

RESUMEN / SUMMARY:  - A case of oral non-Hodgkin’s lymphoma arising in a patient with insulin-dependent diabetes who had undergone renal allograft transplantation is described. The resolution of the disease was achieved by a reduction in her immunosuppressive therapy. The differential diagnosis is discussed, and the management of posttransplantation lymphoproliferative disorders is reviewed.  N. Ref:: 40

 

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[26]

TÍTULO / TITLE:  - The cytology of HIV-induced immunosuppression. Changing pattern of disease in the era of highly active antiretroviral therapy.

REVISTA / JOURNAL:  - Cytopathology 2001 Oct;12(5):281-96.

AUTORES / AUTHORS:  - Kocjan G; Miller R

INSTITUCIÓN / INSTITUTION:  - Department of Histopathology, Royal Free and University College Medical School, University College London, UK.  N. Ref:: 89

 

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[27]

TÍTULO / TITLE:  - Therapeutic drug monitoring of immunosuppressant drugs in clinical practice.

REVISTA / JOURNAL:  - Clin Ther 2002 Mar;24(3):330-50; discussion 329.

AUTORES / AUTHORS:  - Kahan BD; Keown P; Levy GA; Johnston A

INSTITUCIÓN / INSTITUTION:  - Division of Immunology and Organ Transplantation, University of Texas Health Science Center at Houston Medical School, 77030, USA. Barry.D.Kahan@uth.tmc.edu

RESUMEN / SUMMARY:  - BACKGROUND: Therapeutic drug monitoring (TDM) is essential to maintain the efficacy of many immunosuppressant drugs while minimizing their toxicity. TDM has become more refined with the development of new monitoring techniques and more specific assays. OBJECTIVE: This article summarizes current data on TDM of the following immunosuppressant drugs used in organ transplantation: cyclosporine, tacrolimus, sirolimus, everolimus, and mycophenolate mofetil. METHODS: Published data were identified by a MEDLINE search of the English-language literature through March 2001 using the terms therapeutic drug monitoring, cyclosporine, tacrolimus, sirolimus, everolimus, and mycophenolate mofetil. Relevant conference abstracts were also included. RESULTS: TDM of cyclosporine has been well studied, and recent findings indicate that monitoring of drug levels 2 hours after dosing is a more sensitive predictor of outcome than trough (C0) monitoring. C0 levels are being used more widely in TDM of tacrolimus; however, the relationship between C0 and area under the curve has varied widely in clinical trials, with correlations ranging from 0.11 to 0.92. The use of TDM of sirolimus, everolimus, and mycophenolate mofetil is evolving rapidly. CONCLUSIONS: TDM of immunosuppressant drugs that have a narrow therapeutic index is an increasingly useful tool for minimizing drug toxicity while maximizing prevention of graft loss and organ rejection.  N. Ref:: 85

 

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[28]

TÍTULO / TITLE:  - Autoimmune bullous dermatoses in the elderly: diagnosis and management.

REVISTA / JOURNAL:  - Drugs Aging 2003;20(9):663-81.

AUTORES / AUTHORS:  - Mutasim DF

INSTITUCIÓN / INSTITUTION:  - Department of Dermatology, University of Cincinnati, College of Medicine, Cincinnati, Ohio, USA. diya.mutasim@uc.edu

RESUMEN / SUMMARY:  - Elderly individuals are susceptible to autoimmune bullous dermatoses (in particular, pemphigoid, epidermolysis bullosa acquisita and paraneoplastic pemphigus). Bullous dermatoses are associated with high morbidity and mortality. Bullous dermatoses result from autoimmune responses to one or more components of the basement membrane or desmosomes. Pemphigoid results from autoimmunity to hemidesmosomal proteins present in the basement membrane of stratified squamous epithelia. Patients present with tense blisters in flexural areas of the skin. Mild or moderate bullous pemphigoid may be treated with potent topical corticosteroids while extensive disease usually requires systemic corticosteroids or systemic immunosuppressive agents such as azathioprine. Mucosal pemphigoid affects one or more mucous membranes that are lined by stratified squamous epithelia. The two most commonly involved sites are the eye and the oral cavity. Lesions frequently result in scar formation, which may cause blindness. Patients with severe disease or ocular involvement require aggressive therapy with corticosteroids and cyclophosphamide. Epidermolysis bullosa acquisita results from autoimmunity to type VII collagen in the anchoring fibrils of the basement membrane area. Lesions may either arise on an inflammatory base or be non-inflammatory and result primarily from trauma. The inflammatory type of the disease is more responsive to therapy than the non-inflammatory type. Treatment options include corticosteroids, dapsone, cyclosporin, plasmapheresis and immunoglobulin G. Paraneoplastic pemphigus results from autoimmunity to multiple antigens within the desmosomes. The disorder is associated with neoplasms, especially leukaemia and lymphoma. Patients present with severe stomatitis and polymorphous skin eruption. The mucosal and cutaneous involvement may respond to successful treatment of the underlying neoplasm or may require immunosuppressive therapy.  N. Ref:: 122

 

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[29]

TÍTULO / TITLE:  - B19 virus infection in renal transplant recipients.

REVISTA / JOURNAL:  - J Clin Virol. Acceso gratuito al texto completo.

      ●● Enlace a la Editora de la Revista http://www.elsevier.com/gej-ng/29/46/32/show/Products/VIRUSINT/index.htt 

      ●● Cita: J Clinical Virology: <> 2003 Apr;26(3):361-8.

AUTORES / AUTHORS:  - Cavallo R; Merlino C; Re D; Bollero C; Bergallo M; Lembo D; Musso T; Leonardi G; Segoloni GP; Ponzi AN

INSTITUCIÓN / INSTITUTION:  - Virology Unit, Department of Public Health and Microbiology, University of Turin, Via Santena 9, 10126, Turin, Italy. rossana.cavallo@unito.it

RESUMEN / SUMMARY:  - BACKGROUND: B19 virus infection with persistent anaemia has been reported in organ transplant recipients. Detection of B19 virus DNA in serum is the best direct marker of active infection. OBJECTIVE: The present study evaluated the incidence and clinical role of active B19 virus infection in renal transplant recipients presenting with anaemia. STUDY DESIGN: Forty-eight such recipients were investigated by nested PCR on serum samples. The controls were 21 recipients without anaemia. Active HCMV infection was also investigated as a marker of high immunosuppression. RESULTS AND CONCLUSIONS: In 11/48 (23%) patients B19 virus DNA was demonstrated in serum versus only 1/21 (5%) of the controls. Ten of these 11 patients had already been seropositive at transplantation and active infection occurred in eight of them during the first 3 months after transplantation. The remaining patient experienced a primary infection 9 months after transplantation. Eight (73%) of these 11 patients displayed a concomitant HCMV infection and four (36%) showed increasing serum crea