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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 creatinine levels but none developed glomerulopathy; 3/11 (27%) recovered spontaneously from anaemia whereas 8/11 (73%) needed therapy. In conclusion, the relatively high occurrence (23%) of B19 virus infection in patients presenting with anaemia, suggests that it should be considered in the differential diagnosis of persistent anaemia in renal transplant recipients. Presence of the viral DNA should be assessed early from transplantation and the viral load should be monitored to follow persistent infection and better understand the relation between active infection and occurrence of anaemia, and to assess the efficacy of IVIG therapy and/or immunosuppression reduction in clearing the virus.  N. Ref:: 56

 

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[30]

- Castellano -

TÍTULO / TITLE:Nuevos tratamientos inmunodepresores de induccion en el trasplante renal. New induction immunosuppression treatments in kidney transplantation.

REVISTA / JOURNAL:  - Med Clin (Barc). Acceso gratuito al texto completo a partir de los 2 años de la fecha de publicación.

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

      ●● Cita: Medicina Clínica: <> 2001 Jun 30;117(4):147-57.

AUTORES / AUTHORS:  - Pascual J; Ortuno J

INSTITUCIÓN / INSTITUTION:  - Servicio de Nefrologia. Universidad de Alcala. Hospital Ramon y Cajal. Madrid. jpascual@hrc.insalud.es  N. Ref:: 94

 

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[31]

TÍTULO / TITLE:  - Therapeutic monitoring of mycophenolate mofetil in organ transplant recipients: is it necessary?

REVISTA / JOURNAL:  - Clin Pharmacokinet 2002;41(5):319-27.

AUTORES / AUTHORS:  - Mourad M; Wallemacq P; Konig J; de Frahan EH; Eddour DC; De Meyer M; Malaise J; Squifflet JP

INSTITUCIÓN / INSTITUTION:  - Department of Kidney and Pancreas Transplantation, University Hospital Saint Luc, Universite Catholique de Louvain, Brussels, Belgium. Michel.Mourad@chir.ucl.ac.be

RESUMEN / SUMMARY:  - Adequate immunosuppression minimising the risk of organ rejection with acceptable tolerability of the used drugs is a crucial step in organ transplantation. The primary goal is to maintain a consistent time-dependent target concentration by tailoring individual dosage leading to the best efficacy and tolerability combination. The use of therapeutic drug monitoring (TDM) to optimise immunosuppressive therapy is routinely employed for maintenance drugs such as cyclosporin and tacrolimus. The question whether therapeutic monitoring of mycophenolic acid (MPA) in organ transplant recipients treated with mycophenolate mofetil is necessary is not definitely answered. The correlation of mycophenolic acid pharmacokinetic parameters with efficacy and toxicity makes the therapeutic monitoring of this drug promising. However, further studies are mandatory to draw the best guidelines in order to achieve higher levels of evidence that MPA-TDM may improve patient outcome.  N. Ref:: 63

 

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[32]

TÍTULO / TITLE:  - Cicatricial pemphigoid in the upper aerodigestive tract: diagnosis and management in severe laryngeal stenosis.

REVISTA / JOURNAL:  - Ann Otol Rhinol Laryngol 2003 Mar;112(3):271-5.

AUTORES / AUTHORS:  - Boedeker CC; Termeer CC; Staats R; Ridder GJ

INSTITUCIÓN / INSTITUTION:  - Department of Otorhinolaryngology-Head and Neck Surgery, Albert-Ludwigs-University, Freiburg, Germany.

RESUMEN / SUMMARY:  - Pemphigoid is a group of rare, acquired, autoimmune subepithelial blistering diseases. The condition has been subclassified into bullous pemphigoid and cicatricial pemphigoid (CP). Diagnosis is based on clinical presentation, evidence of subepithelialvesicles or bullae on routine histologic analysis, and direct and indirect immunofluorescence studies. Cicatricial pemphigoid is characterized by linear deposition of immunoreactants, principally IgG and complement factor 3, along epithelial basement membranes. Cicatricial pemphigoid usually leads to mucosal scarring. We present a case of severe CP that led to laryngeal and subglottic stenosis and involvement of both eyes and the oral, nasal, and nasopharyngeal mucosae. Treatment with dapsone, corticosteroids, azathioprine sodium, cyclosporine A, cyclophosphamide, methotrexate sodium, and mycophenolate mofetil between 1997 and 2001 only resulted in temporary disease control. The patient has been treated with leflunomide for the past 8 months, and there have been no relapses. Treatment of CP with leflunomide has not been described in the literature until now.  N. Ref:: 25

 

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[33]

TÍTULO / TITLE:  - Atopic diseases of childhood.

REVISTA / JOURNAL:  - Curr Opin Pediatr 2003 Oct;15(5):495-511.

AUTORES / AUTHORS:  - Stone KD

INSTITUCIÓN / INSTITUTION:  - Children’s Hospital Boston, Department of Pediatrics, Harvard Medical School, Massachusetts, USA. kelly.stone@tch.harvard.edu

RESUMEN / SUMMARY:  - PURPOSE OF REVIEW: The incidence of atopic diseases, including atopic dermatitis, allergic rhinitis, and asthma, has increased in developed countries over the past several decades. These diseases comprise a large component of general pediatric practice. This review will highlight some of the recent advances in understanding the pathogenesis and natural history of these diseases, as well as the current approaches to the treatment of children with atopic diseases. RECENT FINDINGS: Recent studies have identified multiple risk factors for the development and progression of atopic diseases. As a result, much research is focused on identifying therapies that can be initiated at a young age to prevent disease progression. New treatment options have become available in recent years, such as topical immunomodulators for atopic dermatitis, leukotriene antagonists for seasonal allergic rhinitis, and alpha-immunoglobulin E therapy for asthma. The importance of viewing allergic rhinitis and asthma as disorders of a single airway has been emphasized. Finally, an update on the national asthma guidelines was recently released in an effort to promote optimal asthma care. SUMMARY: This review summarizes many of the recent advances in the diagnosis and treatment of atopic diseases in children. Although not intended to be a comprehensive review of this broad field, it provides a framework for appreciating the complexity of these diseases and for effectively managing them.  N. Ref:: 180

 

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[34]

TÍTULO / TITLE:  - Molecular diagnosis of an Enterocytozoon bieneusi human genotype C infection in a moderately immunosuppressed human immunodeficiency virus seronegative liver-transplant recipient with severe chronic diarrhea.

REVISTA / JOURNAL:  - J Clin Microbiol. Acceso gratuito al texto completo a partir de los 6 meses de la fecha de publicación.

      ●● Enlace a la Editora de la Revista http://jcm.asm.org/ 

      ●● Cita: J. Clinical Microbiology: <> 2001 Jun;39(6):2371-2.

AUTORES / AUTHORS:  - Sing A; Tybus K; Heesemann J; Mathis A  N. Ref:: 5

 

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[35]

TÍTULO / TITLE:  - Eradication of parvovirus B19 infection after renal transplantation requires reduction of immunosuppression and high-dose immunoglobulin therapy.

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 Oct;17(10):1840-2.

AUTORES / AUTHORS:  - Liefeldt L; Buhl M; Schweickert B; Engelmann E; Sezer O; Laschinski P; Preuschof L; Neumayer HH

INSTITUCIÓN / INSTITUTION:  - Department of Nephrology, Charite, Humboldt-University Berlin, Germany. lutz.liefeldt@charite.de  N. Ref:: 17

 

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[36]

TÍTULO / TITLE:  - Recent advances in immunosuppressive therapy for renal transplantation.

REVISTA / JOURNAL:  - Semin Dial 2001 May-Jun;14(3):218-22.

AUTORES / AUTHORS:  - Peddi VR; First MR

INSTITUCIÓN / INSTITUTION:  - Division of Nephrology and Hypertension, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0585, USA. ram.peddi@uc.edu

RESUMEN / SUMMARY:  - Recent advances in immunosuppression have focused on more effective, safer, and targeted therapies that have resulted in improved short- and intermediate-term renal allograft survival. During the past decade there has been a marked decrease in acute rejection rates following renal transplantation because of the use of newer immunosuppressive agents. Recent data indicate that the average yearly reduction in the relative hazard of graft failure beyond 1 year was 4.2% for all recipients (0.4% for those recipients who had an acute rejection episode and 6.3% for those who did not have an acute rejection). Despite these improvements the currently available immunosuppressive agents are associated with significant cardiovascular risk factors, an increased risk of infection, and the development of malignancies in the long term. Predictive parameters of donor-specific hyporesponsiveness are needed so as to allow identification of patients in whom immunosuppressive therapy can be safely reduced. Immunosuppressive agents that have recently been approved for use in the United States and those that are in clinical and preclinical studies are discussed.  N. Ref:: 27

 

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[37]

TÍTULO / TITLE:  - Recommendations for the implementation of Neoral C(2) monitoring in clinical practice.

REVISTA / JOURNAL:  - Transplantation 2002 May 15;73(9 Suppl):S19-22.

AUTORES / AUTHORS:  - Cole E; Midtvedt K; Johnston A; Pattison J; O’Grady C

INSTITUCIÓN / INSTITUTION:  - University of Toronto, Toronto General Hospital, 621 University Ave., Toronto, Ontario M5G 2C4, Canada.

 

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[38]

TÍTULO / TITLE:  - Role of chiral chromatography in therapeutic drug monitoring and in clinical and forensic toxicology.

REVISTA / JOURNAL:  - Ther Drug Monit 2002 Apr;24(2):290-6.

AUTORES / AUTHORS:  - Williams ML; Wainer IW

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, Leicester University, Leicester, United Kingdom.

RESUMEN / SUMMARY:  - Advances in chiral chromatographic separations have given pharmacologists and toxicologists the tools to examine unexpected clinical results involving chiral drugs. The ability to unravel complex phenomena associated with drug transport and drug metabolism is presented in this manuscript. The relation between the chirality of the drug mefloquine and the intracellular concentrations of the drug cyclosporine is illustrated by examining the effect of the enantiomers of mefloquine on the transport activity of P-glycoprotein (Pgp). These studies were conducted using a liquid chromatographic column containing immobilized Pgp. The results demonstrated that (+)-mefloquine competitively displaced the Pgp substrate cyclosporine whereas (-)-mefloquine had no effect on cyclosporine-Pgp binding. The data suggest that cyclosporine cellular and CNS concentrations can be increased through the concomitant administration of (+)-mefloquine. The use of chirality in clinical and forensic situations is also illustrated by the metabolism of the enantiomers of ketamine (KET). The plasma concentrations of (+)-KET and (-)-KET and the norketamine metabolites (+)-NK and (-)-NK were measured in rat plasma using enantioselective gas chromatography. The separations were accomplished using a gas chromatography chiral stationary phase based on beta-cyclodextrin. The pharmacokinetic profiles of (+)-, (-)-KET and (+)-, (-)-NK were determined in control and protein-calorie malnourished (PCM) rats to determine the effect of PCM on ketamine metabolism and clearance. The results indicate that PCM produced a significant and stereoselective decrease in KET and NK metabolism. The data suggest that the effects of environmental factors (smoking, alcohol use, diet) and drug interactions (coadministered agents) can be measured using the changes in stereochemical metabolic and pharmacokinetic patterns of KET and similar drugs.  N. Ref:: 33

 

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[39]

TÍTULO / TITLE:  - Diffusion-weighted MR imaging of posterior reversible leukoencephalopathy syndrome: a pictorial essay.

REVISTA / JOURNAL:  - Clin Imaging 2003 Sep-Oct;27(5):307-15.

AUTORES / AUTHORS:  - Kinoshita T; Moritani T; Shrier DA; Hiwatashi A; Wang HZ; Numaguchi Y; Westesson PL

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Division of Radiology, University of Rochester Medical Center, 601 Elmwood Avenue Box 648, Rochester, NY 14642, USA. kino@grape.med.tottori-u.ac.jp

RESUMEN / SUMMARY:  - Posterior reversible leukoencephalopathy syndrome is characterized by reversible white matter lesions. However, ischemic injury with irreversible damage may occur. This pictorial essay illustrates MR features associated with posterior reversible leukoencephalopathy syndrome. We will emphasize the role of diffusion-weighted imaging for the discrimination of irreversible ischemic injury from reversible vasogenic edema.  N. Ref:: 9

 

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[40]

TÍTULO / TITLE:  - Monitoring of cellular resistance to cancer chemotherapy.

REVISTA / JOURNAL:  - Hematol Oncol Clin North Am 2002 Apr;16(2):357-72, vi.

AUTORES / AUTHORS:  - Krishan A; Arya P

INSTITUCIÓN / INSTITUTION:  - Radiation Oncology Department, University of Miami Medical School, Division of Experimental Therapeutics (R-71), P.O. Box 01690, Miami, FL 33101, USA. akrishan@med.miami.edu

RESUMEN / SUMMARY:  - Cellular resistance to a broad spectrum of natural products used as antitumor drugs is believed to be a major cause for the failure of chemotherapy. Flow cytometry has been used for monitoring the expression of drug resistance markers, determining accumulation of fluorescent drugs, and for screening of drugs that enhance chemosensitivity by blocking efflux and enhancing drug retention. This article reviews recent developments in our understanding of the multiple drug resistance phenotype and the use of flow cytometry for the study of drug efflux and its modulation in human tumor cells.  N. Ref:: 77

 

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[41]

TÍTULO / TITLE:  - Tailoring immunosuppressive therapy based on donor and recipient risk factors.

REVISTA / JOURNAL:  - Transplant Proc 2001 May;33(3):2207-11.

AUTORES / AUTHORS:  - First MR

INSTITUCIÓN / INSTITUTION:  - University of Cincinnati Medical Center, Cincinnati, Ohio 45267-0585, USA.  N. Ref:: 35

 

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[42]

TÍTULO / TITLE:  - Maintenance immunosuppression in the renal transplant recipient: an overview.

REVISTA / JOURNAL:  - Am J Kidney Dis 2001 Dec;38(6 Suppl 6):S25-35.

AUTORES / AUTHORS:  - Gaston RS

INSTITUCIÓN / INSTITUTION:  - Division of Nephrology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. rgaston@nrtc.uab.edu

RESUMEN / SUMMARY:  - Managing maintenance immunosuppressive regimens after kidney transplantation is often challenging and confusing, requiring careful attention to efficacy, dosing, adverse effects, and costs of multiple medications. Most protocols combine a primary immunosuppressant (cyclosporine or tacrolimus) with one or two adjunctive agents (azathioprine, mycophenolate mofetil, sirolimus, corticosteroids). Avoiding drug-drug interactions is a major part of effective immunosuppressant management, and special situations (eg, pregnancy, intravenous dosing, caring for minority patients) can prove especially daunting. This review summarizes available data regarding current practices in maintenance immunosuppression, emphasizing issues that arise in day-to-day management of renal transplant recipients.  N. Ref:: 69

 

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[43]

TÍTULO / TITLE:  - Advances in the management of psoriasis: monoclonal antibody therapies.

REVISTA / JOURNAL:  - Int J Dermatol 2002 Dec;41(12):827-35.

AUTORES / AUTHORS:  - Mehrabi D; DiCarlo JB; Soon SL; McCall CO

INSTITUCIÓN / INSTITUTION:  - Department of Dermatology, Emory University School of Medicine, Atlanta, GA 30322, USA.

RESUMEN / SUMMARY:  - Psoriasis is a common skin disorder characterized by erythematous, scaling plaques. Until recently, therapies for this disease have been aimed at reducing keratinocyte proliferation. We have learned that psoriasis is not primarily a disorder of keratinocyte hyperproliferation, but is an inflammatory disease. This knowledge, especially our current understanding of the role of activated T cells in psoriasis, has led to new therapeutic options and new areas of research. Immunosuppressive agents such as cyclosporine have proven very useful in the treatment of psoriasis, but their use is limited by toxicity. Monoclonal antibodies directed against key components of the inflammatory process have been studied in an attempt to produce safer, more selective immunosuppressive agents. This review summarizes much of the available literature describing the use of monoclonal antibodies in the treatment of psoriasis.  N. Ref:: 59

 

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[44]

TÍTULO / TITLE:  - Chronic myeloid leukemia: pathophysiology, diagnostic parameters, and current treatment concepts.

REVISTA / JOURNAL:  - Wien Klin Wochenschr 2003 Aug 14;115(13-14):485-504.

AUTORES / AUTHORS:  - Sillaber C; Mayerhofer M; Agis H; Sagaster V; Mannhalter C; Sperr WR; Geissler K; Valent P

INSTITUCIÓN / INSTITUTION:  - Abteilung fur Hamatologie und Hamostaseologie, Universitatsklinik fur Innere Medizin I, AKH-Wien, Austria. christian.sillaber@univie.ac.at

RESUMEN / SUMMARY:  - Chronic myeloid leukemia (CML) is a stem cell disease characterized by excessive accumulation of clonal myeloid (precursor) cells in hematopoietic tissues. CML cells display the translocation t(9; 22) that creates the bcr/abl oncogene. The respective oncoprotein (= BCR/ABL) exhibits constitutive tyrosine kinase activity and promotes growth and survival in CML cells. Clinically, CML can be divided into three phases: the chronic phase (CP), the accelerated phase (AP), and the blast phase (BP) that resembles acute leukemia. Progression to AP and BP is associated with occurrence of additional genetic defects that cooperate with bcr/abl in leukemogenesis and lead to resistance against antileukemic drugs. The prognosis in CML is variable depending on the phase of disease, age, and response to therapy. The only curative approach available to date is stem cell transplantation. For those who cannot be transplanted, the BCR/ABL tyrosine kinase inhibitor STI571 (Glivec, Imatinib), interferon-alpha (with or without ARAC), or other cytoreductive drugs are prescribed. Currently available data show that STI571 is a superior compound compared to other drugs in producing complete cytogenetic and molecular responses. However, despite superior initial data and high expectations for an effect on survival, long term results are not available so far, and resistance against STI571 has been reported. Forthcoming strategies are therefore attempting to prevent or counteract STI571 resistance by co-administration of other antileukemic drugs. Whether these strategies will lead to curative drug therapy in CML in the future remains at present unknown.  N. Ref:: 209

 

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[45]

TÍTULO / TITLE:  - Sequential protocol biopsies from renal transplant recipients show an increasing expression of active TGF beta.

REVISTA / JOURNAL:  - Transpl Int 2002 Dec;15(12):630-4. Epub 2002 Oct 19.

      ●● Enlace al texto completo (gratuito o de pago) 1007/s00147-002-0472-3

AUTORES / AUTHORS:  - Jain S; Mohamed MA; Sandford R; Furness PN; Nicholson ML; Talbot D

INSTITUCIÓN / INSTITUTION:  - University Department of Surgery, Leicester General Hospital, Gwendolen Road, Leicester, LE5 4PW, UK. sj34@le.ac.uk

RESUMEN / SUMMARY:  - Chronic allograft nephropathy (CAN) is a major cause of graft loss after renal transplantation. Implicated in the pathogenesis of this complication is overproduction of the cytokine transforming growth factor beta (TGF beta). In this study we measured changes in CAN’s expression in stable patients early after transplantation, and studied links with established risk factors for CAN, such as delayed graft function, acute rejection, and cyclosporine exposure. We took biopsies from 40 renal allografts at time of transplantation (pre-perfusion), and then, using ultrasound guidance, at 1 week and 6 months after transplantation. An immunofluorescence technique was used to stain sections for active TGF beta. These were then assessed by semi-quantitative scanning laser confocal microscopy. There was very little variation in active TGF-beta expression among patients in their pre-perfusion biopsies. Expression had increased by 1 week and then very significantly by 6 months ( P<0.0001). Patients who suffered delayed graft function had increased TGF-beta expression at both time points. There was no difference regarding donor type, acute rejection, and immunosuppressive drug (cyclosporine or tacrolimus). There was no correlation between the amount of TGF-beta expression at any time-point and isotope glomerular filtration rate (GFR) at 12 months. This study demonstrated that in a group of stable renal allograft recipients, TGF-beta expression in the kidney increased after transplantation. As the study used protocol biopsies, this increase is unlikely to be due to acute events, and probably represents a genuine increase.

 

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[46]

TÍTULO / TITLE:  - Tailoring immunosuppressive therapy in renal transplantation.

REVISTA / JOURNAL:  - Transplant Proc 2002 Sep;34(6):2478-9.

AUTORES / AUTHORS:  - Vathsala A

INSTITUCIÓN / INSTITUTION:  - Department of Renal Medicine, Singapore General Hospital, Singapore.  N. Ref:: 13

 

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[47]

TÍTULO / TITLE:  - Infectious complications in SLE after immunosuppressive therapies.

REVISTA / JOURNAL:  - Curr Opin Rheumatol 2003 Sep;15(5):528-34.

AUTORES / AUTHORS:  - Kang I; Park SH

INSTITUCIÓN / INSTITUTION:  - Section of Rheumatology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. insoo.kang@yale.edu

RESUMEN / SUMMARY:  - Immunosuppressive drugs have become the gold standard for the treatment of major organ involvement in systemic lupus erythematosus. The use of immunosuppressive therapy in systemic lupus erythematosus carries significant risks for infection. This article reviews infectious complications in systemic lupus erythematosus, focusing on effects of immunosuppressive therapy. Patients with systemic lupus erythematosus appear to carry an intrinsically increased risk for infection. Recent studies support this notion further by showing increased risk for serious infections in patients with systemic lupus erythematosus who had mannose-binding lectin deficiency associated with homozygous mannose-binding lectin variant alleles. Patients with systemic lupus erythematosus who were homozygous for mannose-binding lectin variant alleles had a fourfold increase in the incidence of infections, requiring hospitalization. In terms of extrinsic risk factors for infection, use of steroids and cyclophosphamide are the strongest risk factors. The effect of these drugs on infection is also dose dependent. The incidence of infectious complications in patients treated with mycophenolate mofetil, a newly used immunosuppressive drug in systemic lupus erythematosus, appears less frequent compared with cyclophosphamide. Herpes zoster is still the most common viral infection in patients with systemic lupus erythematosus treated with cyclophosphamide and mycophenolate mofetil. Overall data indicate that patients with systemic lupus erythematosus may have intrinsically increased risks for infection that are augmented by immunosuppressive therapies. Cyclophosphamide, in particular in combination with high-dose glucocorticoids, has the strongest effect in suppressing the immune responses against microorganisms. Careful monitoring of infectious complications is warranted in patients with systemic lupus erythematosus receiving immunosuppressive therapies, in particular those on high-dose glucocorticoids and cytotoxic drugs.  N. Ref:: 87

 

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[48]

- Castellano -

TÍTULO / TITLE:Sindrome de cogan atipico: a proposito de dos casos y revision de la literatura. Atypical Cogan’s syndrome: report of two cases and revision of literature.

REVISTA / JOURNAL:  - Acta Otorrinolaringol Esp 2002 Feb;53(2):121-5.

AUTORES / AUTHORS:  - Sanz JJ; Martinez P; Escobar JJ; Menendez LM

INSTITUCIÓN / INSTITUTION:  - Servicio de Otorrinolaringologia, Hospital Clinic, Barcelona.

RESUMEN / SUMMARY:  - Cogan’s syndrome is a rare autoimmune disease with systemic involvement. It appears in young people and has two presentations: the typical form with keratitis, sudden deafness with or without vestibular syndrome, and the atypical form with different non keratitic ocular diseases and a great variety of systemic symptoms in relation with the autoimmune etiology of the process. Cogan’s syndrome has a bad prognosis and deafness appears in 25% of the cases with the right treatment and in 60% of patients without treatment. The best treatment is systemic and ocular corticotherapy. The second treatment of choice is cyclophosphamide or cyclosporine A. We present two cases of atypical Cogan’s syndrome with unilateral deafness in both.  N. Ref:: 11

 

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[49]

TÍTULO / TITLE:  - Cyclosporin: revisions in monitoring guidelines and review of current analytical methods.

REVISTA / JOURNAL:  - Ann Clin Biochem 2002 Sep;39(Pt 5):424-35.

      ●● Enlace al texto completo (gratuito o de pago) 1258/000456302320314430

AUTORES / AUTHORS:  - Andrews DJ; Cramb R

INSTITUCIÓN / INSTITUTION:  - Department of Clinical Biochemistry, University Hospital Birmingham NHS Trust, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, UK.

RESUMEN / SUMMARY:  - This article summarizes the main changes that have occurred in cyclosporin (ciclosporin) monitoring and measurement since the previous review in this journal. Cyclosporin has been reformulated to reduce variability in its absorption, leading to fewer post-transplant rejection episodes. Monitoring has mostly utilized the measurement of pre-dose blood levels of the drug, but more recently the potential benefit of using samples collected during the first few hours post-dose has been evaluated. Calculating the area under the cyclosporin concentration-time curve may be the ideal, but is not viable in the routine clinical situation and 2-h post-dose sampling seems likely to offer a practical clinical solution. Analytical methods based on high-performance liquid chromatography (HPLC) and immunoassay are available for the determination of whole blood cyclosporin concentrations. HPLC is specific but rarely used for routine monitoring, although HPLC-tandem mass spectrometry is making the technique more viable. New immunoassays have been introduced, but none are completely specific for the parent drug and all exhibit cross-reactivity towards cyclosporin metabolites. Immunoassays were originally designed for the lower cyclosporin concentrations seen in pre-dose samples, but are being evaluated and modified for determination of the higher concentrations seen 2 h post-dose.  N. Ref:: 62

 

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[50]

TÍTULO / TITLE:  - Therapeutic monitoring of sirolimus: its contribution to optimal prescription.

REVISTA / JOURNAL:  - Transplant Proc 2003 May;35(3 Suppl):157S-161S.

AUTORES / AUTHORS:  - Holt DW; Denny K; Lee TD; Johnston A

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

RESUMEN / SUMMARY:  - It is now common practice to measure immunosuppressive drugs in blood as a guide to therapy. The immunosuppressive drug sirolimus, recently approved for use following kidney transplantation, was developed in the context of this clinical approach. Throughout the early clinical studies, validated analytical techniques based on chromatographic techniques were used to measure the drug. After a brief period in which an immunoassay was available, routine measurements are again being performed by chromatographic assays. In this article the use of blood concentration measurements in the assessment of the early and pivotal clinical trials of the drug is documented. Then, the rationale for the routine monitoring of the drug in clinical practice, a regulatory requirement in some countries, is set out. It is concluded that the development of this compound has benefited from experience gained during the pharmacokinetic assessment of other immunosuppressive drugs. The pharmacokinetic data accumulated on sirolimus have been a key element in formulating guidelines on dosing with this drug, both when used in combination with cyclosporine and when used after cyclosporine withdrawal.  N. Ref:: 32

 

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[51]

TÍTULO / TITLE:  - Immunosuppressive treatment of acquired aplastic anemia and immune-mediated bone marrow failure syndromes.

REVISTA / JOURNAL:  - Int J Hematol 2002 Feb;75(2):129-40.

AUTORES / AUTHORS:  - Young NS

INSTITUCIÓN / INSTITUTION:  - Hematology Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda. MD 20892-1652, USA.

RESUMEN / SUMMARY:  - Modern therapeutic strategies for the treatment of acquired aplastic anemia are based on the current understanding of its pathophysiology as well as empiric observations. Most cases of aplastic anemia appear to be the result of immune-mediated destruction of hematopoietic cells, which can be approached by stem cell transplantation in younger patients with appropriate histocompatible donors or by immunosuppression to reduce T-cell activity. Popular treatment regimens combine antithymocyte globulin with cyclosporine. Although a majority of patients respond with improved blood counts and achieve transfusion-independence, late clonal complications of myelodysplasia and cytogenetic abnormalities occur in a substantial minority of cases. Additionally, there is no clear algorithm for the treatment of refractory disease. Newer methods of treatment, including high-dose cyclophosphamide and the development of potentially tolerizing combinations of drugs. are under study. Effective therapies for aplastic anemia might also be applied to other T-cell mediated, organ-specific human diseases.  N. Ref:: 129

 

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[52]

TÍTULO / TITLE:  - Evolution of immunosuppression and continued importance of acute rejection in renal transplantation.

REVISTA / JOURNAL:  - Am J Kidney Dis 2001 Dec;38(6 Suppl 6):S2-9.

AUTORES / AUTHORS:  - Chan L; Gaston R; Hariharan S

INSTITUCIÓN / INSTITUTION:  - Department of Renal Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA. Larry.Chan@uchsc.edu

RESUMEN / SUMMARY:  - As steady improvement in short-term kidney graft survival and long-term outcomes prolongs the lives of transplant patients, responsibility for their care is shifting away from transplant specialists and into the hands of community nephrologists. Therefore, community nephrologists need to have a deeper understanding of immunosuppressive therapies than ever before. Pharmacologic immunosuppression has been continuously evolving over the past two decades. Azathioprine was introduced in the early 1960s. Introduction of cyclosporine (CsA) in 1983 revolutionized short-term outcomes after renal transplantation. The first monoclonal antibody immunosuppressant, OKT3, was introduced in 1986. The 1990s saw the introduction of a number of important new agents, including mycophenolate mofetil (MMF), tacrolimus, and a microemulsion CsA, as well as two new monoclonal antibodies. Combinations of these new agents, along with improving clinical care, have produced 1-year patient survival approaching 100% and graft survival exceeding 90%. The newest class of agents, the first of which is sirolimus, is called target of rapamycin (TOR) inhibitors and is used with CsA for maintenance therapy. Immunosuppressive drug therapy after kidney transplantation continues to evolve. There is a variety of pharmacologic combinations from which to choose, based on immunologic risk and side effect profiles. As new regimens are developed, ongoing communications between the transplant center and community nephrologists will be required to implement therapeutic changes and optimize patient care successfully.  N. Ref:: 59

 

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[53]

TÍTULO / TITLE:  - Promising early outcomes with a novel, complete steroid avoidance immunosuppression protocol in pediatric renal transplantation.

REVISTA / JOURNAL:  - Transplantation 2001 Jul 15;72(1):13-21.

AUTORES / AUTHORS:  - Sarwal MM; Yorgin PD; Alexander S; Millan MT; Belson A; Belanger N; Granucci L; Major C; Costaglio C; Sanchez J; Orlandi P; Salvatierra O Jr

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Stanford University Medical Center, 703 Welch Road, Suite H-5, Palo Alto, CA 94304, USA.

RESUMEN / SUMMARY:  - BACKGROUND: Corticosteroids have been a cornerstone of immunosuppression for four decades despite their adverse side effects. Past attempts at steroid withdrawal in pediatric renal transplantation have had little success. This study tests the hypothesis that a complete steroid-free immunosuppressive protocol avoids steroid dependency for suppression of the immune response with its accompanying risk of acute rejection on steroid withdrawal. METHODS: An open labeled prospective study of complete steroid avoidance immunosuppressive protocol was undertaken in 10 unsensitized pediatric recipients (ages 5-21 years; mean 14.4 years) of first renal allografts. Steroids were substituted with extended daclizumab use, in combination with tacrolimus and mycophenolate mofetil. Protocol biopsies were performed in the steroid-free group at 0, 1, 3, 6, and 12 months posttransplantation. Clinical outcomes were compared to a steroid-based group of 37 matched historical controls. RESULTS: Graft and patient survival was 100% in both groups. Clinical acute rejection was absent in the steroid-free group at a mean follow-up time of 9 months (range 3-13.7 months). Protocol biopsies in the steroid-free group (includes 10 patients at 3 months, 7 at 6 months, and 4 at 12 months) revealed only two instances of mild (Banff 1A) subclinical rejection (reversed by only a nominal increase in immunosuppression) and no chronic rejection. At 6 months the steroid-free group had no hypertension requiring treatment (P=0.003), no hypercholesterolemia (P=0.007), and essentially no body disfigurement (P=0.0001). Serum creatinines, Schwartz GFR, and mean delta height Z scores trended better in the steroid-free group. In the steroid-free group, one patient had cytomegalovirus disease at 1 month and three had easily treated herpes simplex stomatitis, but with no significant increase in bacterial infections or rehospitalizations over the steroid-based group. The steroid-free group was more anemic early posttransplantation (P=0.004), suggesting an early role of steroids in erythrogenesis; erythropoietin use normalized hematocrits by 6 months. CONCLUSIONS: Complete steroid-free immunosuppression is efficacious and safe in this selected group of children with no early clinical acute rejection episodes. This protocol avoids the morbid side effects of steroids without increasing infection, and may play a future critical role in avoiding noncompliance, although optimizing renal function and growth.

 

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[54]

TÍTULO / TITLE:  - Improving tolerability of immunosuppressive regimens.

REVISTA / JOURNAL:  - Transplantation 2001 Dec 27;72(12 Suppl):S105-12.

AUTORES / AUTHORS:  - MacDonald A

RESUMEN / SUMMARY:  - CNIs and corticosteroids are associated with adverse effects that can diminish quality of life and detrimentally affect long-term allograft and patient survival. Nephrotoxicity is the major side effect of CNI therapy. A search has been ongoing for improved immunosuppressive regimens that will provide adequate protection against acute allograft rejection, while decreasing the nephrotoxic and other effects associated with CNIs. This paper reviewed the immunosuppressive agent sirolimus as a potential new option in transplantation, focusing on its mechanism of action and clinical efficacy as well as potential antiproliferative and antineoplastic properties. The findings and lessons learned from key clinical studies in which sirolimus was used to augment or replace CNIs and/or corticosteroids were highlighted, and the importance of clinical pharmacokinetics and therapeutic drug monitoring in these regimens were discussed. Preliminary studies of combination therapy with sirolimus and tacrolimus in solid organ transplantation indicate that sirolimus/tacrolimus combination therapy may provide strong protection against acute rejection and diminish the nephrotoxicity associated with CNI-based therapy. Other studies suggest that sirolimus can be used as base immunosuppressive therapy, thereby completely avoiding the nephrotoxicity associated with CNI-based therapies, while continuing to provide powerful protection against rejection. With patients surviving longer with functional allografts, quality of life is becoming an increasing important clinical endpoint in transplantation. The studies reviewed here suggest that sirolimus might be used to improve quality of life significantly without increasing the risk of allograft rejection or shortening patient survival.  N. Ref:: 73

 

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[55]

TÍTULO / TITLE:  - New developments in the immunosuppressive drug monitoring of cyclosporine, tacrolimus, and azathioprine.

REVISTA / JOURNAL:  - Clin Biochem 2001 Feb;34(1):9-16.

AUTORES / AUTHORS:  - Armstrong VW; Oellerich M

INSTITUCIÓN / INSTITUTION:  - Abteilung Klinische Chemie, Zentrum Innere Medizin, Georg-August-Universitat Gottingen, Robert-Koch-Strasse 40, 37075, Gottingen, Germany. varmstro@med.uni-goettingen.de

RESUMEN / SUMMARY:  - The calcineurin inhibitors cyclosporine and tacrolimus form the cornerstones of most immunosuppression protocols. Because of their variable pharmacokinetics, and their narrow therapeutic indices, post-transplant immunosuppressive drug monitoring is an essential part of patient care to minimize the risks of toxicity or acute rejection. Furthermore, a reduction in the rate of acute rejection has been shown to result in a lower rate of graft loss due to chronic rejection. The introduction of the microemulsion formulation of cyclosporine with its more consistent bioavailability has renewed interest in the use of alternative sampling strategies to the trough cyclosporine concentration. Both pharmacokinetic and pharmacodynamic considerations support the concept that determination of cyclosporine during the absorption phase (0-4 h) might offer a better prediction of cyclosporine immunosuppressive efficacy. Initial investigations suggest that monitoring a 2-h postdose concentration C(2) may provide a more efficacious alternative to trough monitoring for optimizing therapy with Neoral. Tacrolimus has a 10- to 100-fold greater in vitro immunosuppressive activity compared with cyclosporine. Consistent with its greater potency, therapeutic whole blood trough concentrations for tacrolimus are around 20-fold lower than the corresponding cyclosporine concentrations. The correlation between toxicity and tacrolimus trough concentrations appears to be stronger than that for acute rejection. The results from a concentration-ranging trial in primary kidney-transplantation and liver-transplantation trials all found a significant relationship between toxicity and tacrolimus trough levels. Azathioprine is converted in vivo to 6-mercaptopurine, which is subsequently metabolized to the pharmacologically active 6-thioguanine nucleotides. The latter are also responsible for the cytotoxic side effects. Reliance on blood counts to monitor azathioprine therapy can be misleading, and they do not provide information on immunosuppresive efficacy. More pertinent information can be obtained through the measurement of thiopurine S-methyltransferase activity and the quantification of intracellular 6-thioguanine nucleotides concentrations in red blood cells. Prospective studies have demonstrated the clinical utility of determining 6-thioguanine nucleotides to individualise immunosuppressive therapy with azathioprine not only in the field of transplantation, but also in inflammatory bowel disease.  N. Ref:: 55

 

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[56]

TÍTULO / TITLE:  - Liver biopsy, viral kinetics, and the impact of viremia on severity of hepatitis C virus recurrence.

REVISTA / JOURNAL:  - Liver Transpl 2003 Nov;9(11):S58-62.

      ●● Enlace al texto completo (gratuito o de pago) 1053/jlts.2003.50245

AUTORES / AUTHORS:  - Charlton M

INSTITUCIÓN / INSTITUTION:  - Division of Gastroenterology and Hepatology, Mayo Clinic and Foundation, Rochester, MN 55905, USA. charlton.michael@mayo.edu

RESUMEN / SUMMARY:  - 1. Nearly all recipients who are chronically infected with hepatitis C virus (HCV) at the time of liver transplantation will have HCV RNA detectable postoperatively. 2. HCV replication can begin as early as the first postoperative week. 3. HCV levels fall significantly during the anhepatic phase of liver transplantation and continue to fall during the first 12-24 hours posttransplantation. 4. Serum HCV RNA levels typically increase rapidly from the second week posttransplantation and peak by the fourth postoperative month. HCV RNA levels at one year posttransplantation are 10-20 fold greater than pretransplant levels. 5. Corticosteroid treatment for acute cellular rejection is associated with large increases in HCV RNA levels. 6. HCV RNA levels do not appear to vary with choice of calcineurin inhibitor. 7. Early HCV RNA levels are predictive of subsequent histological severity of recurrence. 8. A correlation between early levels of viremia and subsequent allograft injury suggests that initiation of antiviral therapy early in the posttransplant course might be desirable.  N. Ref:: 31

 

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[57]

TÍTULO / TITLE:  - An alternative mechanism for the immunosuppressive effect of transfusion.

REVISTA / JOURNAL:  - Vox Sang 2002 Aug;83 Suppl 1:417-9.

AUTORES / AUTHORS:  - Dzik WH; Mincheff M; Puppo F

INSTITUCIÓN / INSTITUTION:  - Blood Transfusion Service, J-224, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. sdzik@partners.org  N. Ref:: 15

 

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[58]

TÍTULO / TITLE:  - How to manage patients with lupus nephritis.

REVISTA / JOURNAL:  - Best Pract Res Clin Rheumatol 2002 Apr;16(2):195-210.

      ●● Enlace al texto completo (gratuito o de pago) 1053/berh.2001.0221

AUTORES / AUTHORS:  - Esdaile JM

INSTITUCIÓN / INSTITUTION:  - Division of Rheumatology, University of British Columbia, Canada.

RESUMEN / SUMMARY:  - The clinical and renal biopsy predictors of assistance in determining therapy are reviewed. While pulse cyclophosphamide remains the most effective treatment for proliferative nephritis, there is increasing interest in other agents, such as azathioprine, particularly to maintain remission. While lupus membranous nephropathy has attracted limited study, preliminary work suggests a role for cyclophosphamide. Newer therapies, including cyclosporine A, mycophenolate mofetil, immunoadsorption, intravenous immune globulin, LJP-394, high-dose immunoablation and nucleoside analogues require further study but offer hope for those failing conventional treatments.  N. Ref:: 60

 

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[59]

TÍTULO / TITLE:  - Single-agent immunosuppression after liver transplantation: what is possible?

REVISTA / JOURNAL:  - Drugs 2002;62(11):1587-97.

AUTORES / AUTHORS:  - Raimondo ML; Burroughs AK

INSTITUCIÓN / INSTITUTION:  - Liver Transplantation and Hepato-Biliary Medicine, Royal Free Hospital, Hampstead, London, UK.

RESUMEN / SUMMARY:  - Orthotopic liver transplantation is a life saving and life enhancing procedure. The development of immunosuppressive drugs has contributed to the high rate of success in terms of both patient and graft survival. However, the considerable adverse effects of these therapies are affecting long-term outcomes of transplant recipients. Complications related to immunosuppression are responsible for the majority of deaths in patients surviving more than 1 year. Therefore, the search for an optimal immunosuppressive regimen has become of paramount importance. The liver has proved to be an ‘immunologically privileged’ organ, capable in several animal models to be accepted as an allograft without any intervention on the immune system of the recipient. In some human liver allografts acceptance of the new organ is recognised after withdrawal of immunosuppressants, but prior identification of such individuals is not yet possible, thus negating this management option. Graft-recipient interaction is peculiar in liver transplantation: acute cellular rejection does not always need to be treated, and if it is not severe, appears to be associated with a better survival of both patient and graft. In the last decade there has been an evolution of immunosuppressive protocols, driven by empirical observation and a deeper understanding of immunological events after transplant. However, most modifications have been made because of the necessity to reduce long-term drug related morbidity and mortality. Withdrawal of corticosteroids has proven to be safely achievable in most patients, with no deleterious effects on patient or graft survival but with a great benefit in terms of reduction of incidence of metabolic and cardiovascular complications. Long-term ‘steroid-free’ regimens are therefore now widely used. Patients with stable graft function can be easily maintained using a single drug usually after 6 or 12 months and usually with a calcineurin inhibitor. The more evolved step of using monotherapy ab initio has also proven to be effective in a few studies and needs to be explored further. In the future new strategies will be designed to help the development of tolerance of the allograft, selectively stimulating instead of suppressing the immune reaction of the recipient.  N. Ref:: 51

 

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[60]

TÍTULO / TITLE:  - Two-hour cyclosporine concentration determination: an appropriate tool to monitor neoral therapy?

REVISTA / JOURNAL:  - Ther Drug Monit 2002 Feb;24(1):40-6.

AUTORES / AUTHORS:  - Oellerich M; Armstrong VW

INSTITUCIÓN / INSTITUTION:  - Department of Clinical Chemistry, Georg-August University, Gottingen, Germany. moeller@med.uni-goettingen.de

RESUMEN / SUMMARY:  - Cyclosporine is a critical dose drug for which individualisation by therapeutic drug monitoring is indisputable. Current evidence suggests that a single concentration (C2) taken two hours after cyclosporine administration with the microemulsion formulation better predicts exposure and events than the trough concentration (C(0)), which is routinely used for adjusting the dosage of this drug. Studies have shown that the greatest calcineurin inhibition and the maximum inhibition of IL-2 production occur in the first 1 to 2 hours after dosing. These findings support the concept that the C2 level better reflects immunosuppressive efficacy than the trough concentration. Preliminary data from an outcome study in liver transplant recipients have shown that the incidence of biopsy proven moderate to severe acute rejection was significantly lower in patients managed by C2 monitoring compared with those monitored by C(0). The critical importance of achieving adequate cyclosporine exposure during the first 3 to 5 posttransplant days to prevent acute rejection has been documented in prospective studies with de novo renal and liver transplant recipients. Conversion of maintenance liver and heart transplant patients to C2 monitoring resulted in an amelioration of renal function. Time-dependent target values have been proposed for liver and renal transplant recipients. These require further prospective validation. For routine monitoring of C2 levels on-site validated dilution guidelines are necessary for most of the available immunoassays. C2 monitoring necessitates further organizational requirements which may be judged differently between transplant centers. In particular during the early posttransplant period C2 monitoring is a promising new option to make immunosuppressive therapy with the microemulsion formulation of cyclosporine safer and more efficient.  N. Ref:: 38

 

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[61]

TÍTULO / TITLE:  - Therapeutic drug monitoring of immunosuppressive drugs in kidney transplantation.

REVISTA / JOURNAL:  - Curr Opin Nephrol Hypertens 2002 Nov;11(6):657-63.

      ●● Enlace al texto completo (gratuito o de pago) 1097/01.mnh.0000040053.33359.26

AUTORES / AUTHORS:  - Holt DW

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

RESUMEN / SUMMARY:  - PURPOSE OF REVIEW: Drug monitoring has become an accepted adjunct to optimizing therapy with immunosuppressive drugs. This review assesses publications that relate to the analytical techniques used to measure cyclosporin, tacrolimus, mycophenolic acid, sirolimus and everolimus, as well as the clinical data obtained for these drugs. For all of these drugs there has been a substantial and continuing investment in assessing the clinical value of drug monitoring. RECENT FINDINGS: Fundamental controversies still persist regarding which time point to use for monitoring. The most significant single development has been the move towards using a timed blood sample 2 h after drug administration (C2) to monitor cyclosporin therapy with the Neoral formulation. The favourable clinical results obtained with this approach have had an impact on reevaluating monitoring data for some of the other drugs. The newest drugs to reach clinical evaluation, sirolimus and everolimus, have been studied in the context of concentration-controlled dosing and there is a good rationale for their measurement. There have also been developments in the analytical techniques used, mostly to improve the selectivity of the assays or to adapt them to new monitoring strategies. SUMMARY: Interpretation of drug concentration data is becoming ever more complex in this field as the number of potential drug combinations expands. The relatively narrow therapeutic index of these agents and the ever-present risk of clinically significant pharmacokinetic drug interactions makes drug monitoring an important aspect of their prescription.  N. Ref:: 77

 

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[62]

TÍTULO / TITLE:  - An induction versus no-induction protocol in anticalcineurin-based immunosuppression using very low-dose steroids.

REVISTA / JOURNAL:  - Transplant Proc 2001 Jun;33(4 Suppl):3S-10S.

AUTORES / AUTHORS:  - Charpentier B

INSTITUCIÓN / INSTITUTION:  - University Hospital of Bicetre, Le Kremlin-Bicetre, France.

 

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[63]

TÍTULO / TITLE:  - Induction versus non-induction protocols in anti-calcineurin-based immunosuppression.

REVISTA / JOURNAL:  - Transplant Proc 2001 Nov-Dec;33(7-8):3334-6.

AUTORES / AUTHORS:  - Charpentier B

INSTITUCIÓN / INSTITUTION:  - Service de Nephrologie, University Hospital of Bicetre, Bicetre, France.

 

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[64]

TÍTULO / TITLE:  - Immunosuppressant drugs—the role of therapeutic drug monitoring.

REVISTA / JOURNAL:  - Br J Clin Pharmacol 2001;52 Suppl 1:61S-73S.

AUTORES / AUTHORS:  - Johnston A; Holt DW

INSTITUCIÓN / INSTITUTION:  - Department of Clinical Pharmacology, St Bartholomew’s and The Royal London School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ, UK. A.Johnston@mds.qmw.ac.uk  N. Ref:: 164

 

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[65]

TÍTULO / TITLE:  - The development of immunosuppression: the rapamycin milestone.

REVISTA / JOURNAL:  - Transplant Proc 2003 May;35(3 Suppl):15S-17S.

AUTORES / AUTHORS:  - Calne RY

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, University of Cambridge, Addenbrook Hospital, Cambridge, UK.  N. Ref:: 22

 

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[66]

TÍTULO / TITLE:  - Chromomycosis due to Exophiala jeanselmei in a renal transplant recipient.

REVISTA / JOURNAL:  - Eur J Dermatol 2003 May-Jun;13(3):305-7.

AUTORES / AUTHORS:  - Pena-Penabad C; Duran MT; Yebra MT; Rodriguez-Lozano J; Vieira V; Fonseca E

INSTITUCIÓN / INSTITUTION:  - Department of Dermatology, Complejo Hospitalario Juan Canalejo, Servicio de Dermatologia, Xubias de Arriba, 84, 15006. a Coruna, España.

RESUMEN / SUMMARY:  - Chromomycosis is a rare mycotic infection that is more frequent in tropical and subtropical regions. Dematiaceous fungi are the causal agents of this mycosis. Several cases of chromomycosis in organ transplant recipients have been reported. We present a case of chromomycosis by Exophiala jeanselmei in a Spanish male who had received a renal transplant several months previously, and was receiving treatment with tacrolimus, prednisone and mycophenolate mofetil. Very few cases of chromomycosis due to Exophiala have been reported, and this is, to our knowledge, the first European case.  N. Ref:: 16

 

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[67]

TÍTULO / TITLE:  - Intracranial hemorrhage in neuro-Behcet’s syndrome.

REVISTA / JOURNAL:  - Intern Med 2002 Sep;41(9):692-5.

AUTORES / AUTHORS:  - Kikuchi S; Niino M; Shinpo K; Terae S; Tashiro K

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, Hokkaido University Graduate School of Medicine, Sapporo.

RESUMEN / SUMMARY:  - OBJECTIVE: Most cerebrovascular disturbances in Behcet’s syndrome are occlusive in nature, while hemorrhage is rare. In this paper, we report three cases of neuro-Behcet’s syndrome presenting with intracerebral hemorrhaging, and discuss the possible causes as they relate to cyclosporine treatment. PATIENTS: Three cases of neuro-Behcet’s syndrome presented with intracranial hemorrhage. One patient had been taking cyclosporine, and the other two patients had never taking cyclosporine. RESULTS: Together with previous reports, these cases suggest that there are two types of intracranial hemorrhage in neuro-Behcet’s syndrome. One type occurs in the center of a lesion and during the acute phase of the disease, while the other occurs in the peripheral lesion and during the subacute phase. CONCLUSIONS: It appears that the intracranial hemorrhages in neuro-Behcet’s syndrome can be divided into two groups. It is possible that the vascular pathologies caused by Behcet’s syndrome and by cyclosporine conspire to induce CNS hemorrhaging in some cases.  N. Ref:: 19

 

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[68]

TÍTULO / TITLE:  - Acquired anti-FVIII inhibitors in children.

REVISTA / JOURNAL:  - Haemophilia 2002 Jan;8(1):28-32.

AUTORES / AUTHORS:  - Moraca RJ; Ragni MV

INSTITUCIÓN / INSTITUTION:  - The Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh Medical Center, PA, USA.

RESUMEN / SUMMARY:  - Acquired inhibitors to FVIII (anti-FVIII) are uncommon in children. An acquired anti-FVIII developed in a previously healthy 4-year-old boy treated with penicillin for streptococcal pharyngitis. Aspirin prophylaxis begun for suspected rheumatic fever led to compartment syndromes of all four extremities, which resolved with high-dose FVIII and surgical decompression. Anti-FVIII in this patient, and the five additional cases identified in a survey of 160 haemophilia treatment centres, occurred at a median age of 8 years, with median initial and peak titres of 4.6 and 6.9 Bethesda Units (BU), respectively. All six presented with bleeding, including haematomas (three intramuscular, one intracranial), and ecchymoses in three. The median baseline FVIII was 0.05 U mL(-1), and the median baseline activated partial thromboplastin time (APTT) was 79.8 s. The inhibitor resolved completely in five patients (83%) within a median 5 months, after treatment with FVIII concentrate, steroids, cytoxan, methotrexate, and no treatment. The inhibitor persisted in the patient with Goodpasture’s disease, despite steroids, cytoxan, cyclosporin, and intravenous gamma globulin. Aspirin therapy, in two, worsened ongoing bleeding. The association of penicillin-like drugs in this and three other cases in the literature suggest that to avoid potential catastrophic bleeding, it is prudent to obtain an APTT prior to initiating aspirin for suspected rheumatic fever. In conclusion, acquired anti-FVIII inhibitors in children may cause severe bleeding, and remit in the majority after FVIII and/or immunosuppressive therapy.  N. Ref:: 21

 

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[69]

TÍTULO / TITLE:  - Cutaneous T-cell lymphoma in a cardiac transplant recipient.

REVISTA / JOURNAL:  - Tex Heart Inst J. Acceso gratuito al texto completo.

      ●● Enlace a la Editora de la Revista http://texasheartinstitute.org/journal.html 

      ●● Cita: Texas Heart Institute Journal: <> 2001;28(3):203-7.

AUTORES / AUTHORS:  - McMullan DM; Radovaneevic B; Jackow CM; Frazier OH; Duvic M

INSTITUCIÓN / INSTITUTION:  - Texas Heart Institute and St Luke s Episcopal Hospital Houston, 77225-0345, USA.

RESUMEN / SUMMARY:  - Mycosis fungoides, an uncommon form of cutaneous T-cell lymphoma, arises in the skin and frequently progresses to generalized lymphadenopathy Although the cause of cutaneous T-cell lymphoma is unknown, chronic immunosuppression may play a role. A few cases have been reported in renal transplant recipients; however, ours appears to be the 1st report of cutaneous T-cell lymphoma in a cardiac transplant recipient. In our patient, cutaneous manifestations of the disease were noted less than 1 year after transplantation. Seven years after transplantation, Sezary syndrome, a variant form of mycosis fungoides, was diagnosed by tissue biopsy and flow cytometry analysis. Photopheresis improved symptoms but was not well tolerated because of hemodynamic sequelae. Psoralen and ultraviolet A therapy also improved the patient’s skin condition, but a generalized lymphadenopathy developed. The maintenance immunosuppressive regimen was changed from cyclosporine (3 mg/kg/day) and azathioprine to cyclosporine (1.5 mg/kg/day) and cyclophosphamide. Although effective in the short-term, the results of this therapeutic strategy could not be fully evaluated because the patient died of acute myocardial infarction.  N. Ref:: 25

 

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[70]

TÍTULO / TITLE:  - Cyclosporin monitoring in Australasia: 2002 update of consensus guidelines.

REVISTA / JOURNAL:  - Ther Drug Monit 2002 Dec;24(6):677-88.

AUTORES / AUTHORS:  - Morris RG; Ilett KF; Tett SE; Ray JE; Fullinfaw RO; Cooke R; Cook S

INSTITUCIÓN / INSTITUTION:  - Department of Cardiology and Clinical Pharmacology, The Queen Elizabeth Hospital, Woodville, South Australia, Australia.

RESUMEN / SUMMARY:  - Therapeutic drug monitoring of cyclosporin (CsA) has been established as part of the routine clinical treatment of patients following organ transplantation for more than 20 years, and based on contemporary knowledge, many consensus guidelines have been published to assist clinics and laboratories attain optimal strategies for patient care. This article addresses the newer directions in CsA monitoring, with particular reference to the Australasian situation that has evolved since the 1993 Australasian guideline. These changes have included the introduction of alternative assay methodologies, changed CsA formulation from Sandimmun to Neoral throughout Australasia, and alternatives to trough concentration (C0) monitoring, especially 2-hour concentration (C2) monitoring and associated validated dilution protocols to accurately quantitate the higher whole blood CsA concentrations. The revision was prepared following a recent survey of all Australasian CsA-monitoring laboratories where discordant practices were evident.

 

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[71]

TÍTULO / TITLE:  - Therapeutic drug monitoring for immunosuppressants.

REVISTA / JOURNAL:  - Clin Chim Acta 2001 Nov;313(1-2):241-53.

AUTORES / AUTHORS:  - Wong SH

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Medical College of Wisconsin, and Dynacare Laboratories, Milwaukee, WI 53206, USA. shwong@mcw.edu

RESUMEN / SUMMARY:  - BACKGROUND: Immunosuppressants have significantly increased patient survival, e.g. in renal transplant up to 90% for the first year. METHODS: Four immunosuppressants are used for clinical applications in the United States: cyclosporine (CsA) (Sandimmune and Neoral), FK 506-tacrolimus (ProGraf), mycophenolic mofetil (CellCept)--the prodrug for the mycophenolic acid (MPA), and rapamycin (RAPA) (Sirolimus). For CsA and FK 506, the rationale for monitoring is due to the variable pharmacokinetics, acute infection, dosage adjustment, non-compliance check, and for long-term maintenance therapy. Targeted whole blood concentrations ranges are: for CsA, 100-400 ng/ml depending on the methods, therapy and organs; and for FK 506, 5-20 ng/ml. For MPA, drug bioavailability—the plasma area-under-curve up to 12 h of 32.2-60.6 mg h/l was correlated to the biopsy-proven rejection rate of <10%. Monitoring is advocated for liver and renal transplants, for pediatrics, and for checking for non-compliance. RAPA monitoring is useful to check for variable pharmacokinetics, for non-compliance and others. The therapeutic range is tentatively targeted for 5-15 ng/ml. Monitoring methodologies are: for CsA, immunoassays such as fluorescence polarization immunoassay, and liquid chromatography (LC); for FK 506, microparticle enzyme immunoassay (MEIA); for MPA, enzyme multiplied immunoassay and LC; and for RAPA, MEIA, LC and LC-mass spectrometry. Proficiency survey programs for CsA and FK 506 are available from the US and Europe. CONCLUSIONS: Monitoring of immunosuppressants has become an essential adjunct to the drug therapy for organ transplant patients.  N. Ref:: 93

 

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[72]

TÍTULO / TITLE:  - Cyclosporine therapeutic drug monitoring.

REVISTA / JOURNAL:  - Transplant Proc 2001 Sep;33(6):3003-5.

AUTORES / AUTHORS:  - Jensen SA; Dalhoff KP

INSTITUCIÓN / INSTITUTION:  - Department of Clinical Pharmacology, Rigshospitalet, Copenhagen, Denmark. sastrup@rh.dk  N. Ref:: 36

 

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[73]

TÍTULO / TITLE:  - Homocysteine levels among transplant recipients: effect of immunosuppressive protocols.

REVISTA / JOURNAL:  - Transplant Proc 2001 Sep;33(6):2945-6.

AUTORES / AUTHORS:  - Mor E; Helfmann L; Lustig S; Bar-Nathan N; Yussim A; Sela BA

INSTITUCIÓN / INSTITUTION:  - Department of Transplantation, Rabin Medical Center, Petach-Tikva, Israel.

 

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[74]

TÍTULO / TITLE:  - Protocol biopsy program after renal transplantation: structure and first results.

REVISTA / JOURNAL:  - Transplant Proc 2002 Sep;34(6):2238-9.

AUTORES / AUTHORS:  - Schwarz A; Mengel M; Gwinner W; Eisenberger U; Hiss M; Radermacher J; Fiebeler A; Abou-Rebyeh F; Haller H

INSTITUCIÓN / INSTITUTION:  - Nephrology Department, Hanover Medical School, Hanover, Germany.

 

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[75]

TÍTULO / TITLE:  - Histopathological findings of 10-year protocol biopsy in pediatric kidney transplant recipients.

REVISTA / JOURNAL:  - Transplant Proc 2002 Dec;34(8):3130-1.

AUTORES / AUTHORS:  - Kamimaki I; Shishido S; Ikeda M; Honda M

INSTITUCIÓN / INSTITUTION:  - Division of Pediatrics, Clinical Research Department, National Saitama Hospital, Saitama, Japan.

 

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[76]

TÍTULO / TITLE:  - Diagnosis and management of refractoriness to platelet transfusion.

REVISTA / JOURNAL:  - Blood Rev 2001 Dec;15(4):175-80.

      ●● Enlace al texto completo (gratuito o de pago) 1054/blre.2001.0164

AUTORES / AUTHORS:  - Schiffer CA

INSTITUCIÓN / INSTITUTION:  - Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA. schiffer@karmanos.org

RESUMEN / SUMMARY:  - Improvements in the availability and quality of platelet transfusions have markedly reduced the morbidity and mortality associated with intensive myelosuppressive therapy. Alloimmunization and refractoriness to platelet transfusion remains a significant clinical problem, although the incidence of alloimmunization may be declining due to more widespread use of leucocyte depleted products. Alloimmunization can be distinguished from other causes of poor post transfusion increments by the measurement of lymphocytotoxic or antiplatelet antibodies. In addition to medical approaches to reduce the risk of bleeding in individual patients, identification of histocompatible donors can usually be accomplished by HLA matching of donor and recipient, platelet cross matching or a combination of both techniques. There are a number of selection strategies which can be utilized and optimal patient management requires close cooperation and communication between clinicians and blood centers.  N. Ref:: 48

 

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[77]

TÍTULO / TITLE:  - New concepts in cyclosporine monitoring.

REVISTA / JOURNAL:  - Curr Opin Nephrol Hypertens 2002 Nov;11(6):619-26.

      ●● Enlace al texto completo (gratuito o de pago) 1097/01.mnh.0000040047.33359.86

AUTORES / AUTHORS:  - Keown PA

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, University of British Columbia, Vancouver, Canada. keown@interchange.ubc.ca

RESUMEN / SUMMARY:  - PURPOSE OF REVIEW: Inadequate cyclosporine exposure is a key risk factor for acute rejection, and may contribute to the development of chronic rejection and graft failure. Pre-dose monitoring does not accurately measure drug exposure because of extensive inter- and intra-patient variability in cyclosporine absorption and metabolism. Limited sampling, using individual timed specimens, offers a new, simple and accurate alternative for clinical monitoring of cyclosporine. RECENT FINDINGS: The area under the first 4 h of the concentration-time curve (AUC ) and the single-point concentration at 2 h post-dose (C2) are key measures of cyclosporine exposure. De novo studies show that achieving an AUC value of more than 4400 microg.h/l or a C2 level of 1500-2000 microg/l during the first 5 days post-transplant minimizes the risk of rejection and improves graft function. Maintenance studies suggest that reducing the C2 level to approximately 800 microg/l after 3-6 months may improve the serum creatinine level, blood pressure, general well-being and reduce adverse effects. SUMMARY: Single-point C2 monitoring can be implemented quickly and simply with appropriate site and patient training. The timing of phlebotomy is more critical, but immunoassay bias is lower with 2 h post-dose than with trough level measures. Single-point C2 monitoring may be effective in liver and heart replacement, but initial target levels for liver transplantation are lower because cyclosporine is transported directly to the liver via the portal system. C2 monitoring is now being widely adopted as an accurate and practical measure of drug exposure, and can be combined with pharmacodynamic methods to optimize immunosuppression.  N. Ref:: 76

 

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[78]

TÍTULO / TITLE:  - Impact of immunosuppressive regimes on posttransplant diabetes mellitus.

REVISTA / JOURNAL:  - Transplant Proc 2001 Aug;33(5A Suppl):23S-26S.

AUTORES / AUTHORS:  - Weir M

INSTITUCIÓN / INSTITUTION:  - Division of Nephology, University of Maryland Hospital, Baltimore, Maryland 21201, USA.  N. Ref:: 44

 

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[79]

TÍTULO / TITLE:  - Posterior leukoencephalopathy syndrome.

REVISTA / JOURNAL:  - Postgrad Med J 2001 Jan;77(903):24-8.

AUTORES / AUTHORS:  - Garg RK

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.

RESUMEN / SUMMARY:  - Posterior leukoencephalopathy syndrome is a newly recognised brain disorder that predominantly affects the cerebral white matter. Oedematous lesions particularly involve the posterior parietal and occipital lobes, and may spread to basal ganglia, brain stem, and cerebellum. This rapidly evolving neurological condition is clinically characterised by headache, nausea and vomiting, seizures, visual disturbances, altered sensorium, and occasionally focal neurological deficit. Posterior leukoencephalopathy syndrome is often associated with an abrupt increase in blood pressure and is usually seen in patients with eclampsia, renal disease, and hypertensive encephalopathy. It is also seen in the patients treated with cytotoxic and immunosuppressive drugs such as cyclosporin, tacrolimus, and interferon alfa. The lesions of posterior leukoencephalopathy are best visualised with magnetic resonance (MR) imaging. T2 weighted MR images, at the height of symptoms, characteristically show diffuse hyperintensity selectively involving the parieto-occipital white matter. Occasionally the lesions also involve the grey matter. Computed tomography can also be used satisfactorily to detect hypodense lesions of posterior leukoencephalopathy. Early recognition of this condition is of paramount importance because prompt control of blood pressure or withdrawal of immunosuppressive agents will cause reversal of the syndrome. Delay in the diagnosis and treatment can result in permanent damage to affected brain tissues.  N. Ref:: 30

 

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[80]

TÍTULO / TITLE:  - C2 monitoring strategy for optimising cyclosporin immunosuppression from the Neoral formulation.

REVISTA / JOURNAL:  - BioDrugs 2001;15(5):279-90.

AUTORES / AUTHORS:  - Levy GA

INSTITUCIÓN / INSTITUTION:  - Multi-Organ Transplantation, The Toronto Hospital, Toronto, Ontario, Canada. fg12@email.msn.com

RESUMEN / SUMMARY:  - Profiling of absorption of cyclosporin microemulsion (Neoral) is a concept in therapeutic drug monitoring (TDM) designed to further optimise the clinical benefits of this formulation in transplant recipients. A single blood concentration measurement 2 hours after Neoral administration (C2) has been shown in both liver and kidney transplant recipients to be a significantly more accurate predictor of drug exposure than trough concentrations (C0), and its use results in a reduction in the incidence and severity of cellular rejection. In a prospective trial in de novo renal transplant recipients, patients who achieved target concentrations for area under the concentration-time curve over the first 4 hours postdose (AUC(0-4h)) of 4500 to 5500 ng. h/ml within 5 days of transplantation had a 7% incidence of histological acute rejection, compared with 37% rejection in those patients who did not achieve this target level. Of the single sampling points, C2 correlates best with AUC(0-4h) (r2 = 0.86); C(0) had the poorest correlation. In an international study in 21 centres examining the absorption profiling, C2 samples were the most accurate predictors of AUC(0-4h) and freedom from rejection. In liver transplant recipients receiving Neoral -based maintenance immunosuppression, adoption of Neoral C2 monitoring identifies patients who are both over- and under-dosed, which is not distinguished by C0 measurements. Further adjustment of C2 to recommended targets, even at 5 and 10 years after transplantation, results in reduction in nephrotoxicity without exposing the patient to the risk of rejection. In summary, despite a level of simplicity comparable to C0 measurement, Neoral absorption profiling, and specifically C2 measurement, is a much more sensitive approach to assessing the pharmacokinetics and predicting the clinical effect of this formulation in the individual patient, with a consequent marked reduction in the incidence of acute cellular rejection and improved long term graft function.  N. Ref:: 23

 

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[81]

TÍTULO / TITLE:  - Prevention and treatment of severe hemodynamic compromise in pediatric heart transplant patients.

REVISTA / JOURNAL:  - Paediatr Drugs 2002;4(11):705-15.

AUTORES / AUTHORS:  - Costello JM; Pahl E

INSTITUCIÓN / INSTITUTION:  - Division of Pulmonary and Critical Care Medicine, Department of Pediatrics, The Children’s Memorial Hospital, Feinberg School of Medicine at Northwestern University, Chicago, Illinois 60614, USA.

RESUMEN / SUMMARY:  - Allograft rejection is a leading cause of severe hemodynamic compromise in pediatric heart transplant patients. A triple-drug immunosuppression regimen, which includes a calcineurin inhibitor, antiproliferative agent, and corticosteroid, suppresses the immune system at multiple different levels for optimal graft protection while minimizing the adverse effects of any one particular agent. Some pediatric centers also use induction therapy with anti-T cell antibodies immediately following transplantation as additional rejection prophylaxis. These antibodies augment immunosuppression by either depleting the T cell pool or blocking interleukin-2 receptors on activated T cells. Despite the aggressive preventive measures outlined above, some pediatric heart transplant patients will develop severe hemodynamic compromise, most commonly due to fulminant rejection. Such patients require attention to, and optimization of, the four determinants of cardiac output (heart rate, preload, contractility and afterload) to stabilize the circulation until the rejection can be reversed. Careful administration of volume, diuretics, inotropes, and afterload-reducing agents will meet this goal. Patients with allograft rejection require augmentation of immune suppression to facilitate myocardial recovery. Corticosteroids form the cornerstone of treatment for both cellular and vascular rejection. In patients with refractory cellular rejection, conversion to mycophenolate mofetil or tacrolimus may be appropriate if these agents are not already being used for maintenance immunosuppression. Critically ill patients may additionally benefit from muromonab-CD3 (OKT3) to augment lympholysis. Treatment employed specifically for humoral rejection is prescribed with the intention of suppressing new antibody formation, removing circulating antibody, and improving coronary blood flow. In addition to corticosteroids, cyclophosphamide and antithymocyte globulin or muromonab-CD3, along with plasmapheresis, may improve survival. Systemic heparinization should be considered to minimize coronary thrombosis in patients with humoral rejection. In the future, novel immunosuppressive agents may further assist in the prevention as well as treatment of severe hemodynamic compromise due to rejection in pediatric heart transplant recipients.  N. Ref:: 99

 

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[82]

TÍTULO / TITLE:  - Polymorphisms in immunoregulatory genes: towards individualized immunosuppressive therapy?

REVISTA / JOURNAL:  - Am J Pharmacogenomics 2002;2(1):13-23.

AUTORES / AUTHORS:  - Daly AK; Day CP; Donaldson PT

INSTITUCIÓN / INSTITUTION:  - Centre for Liver Research, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. A.K.Daly@ncl.ac.uk

RESUMEN / SUMMARY:  - In organ transplantation, successful immunosuppression requires that both rejection and infection episodes be minimized. Unfortunately it is currently impossible to predict individual dose requirement for immunosuppressive drugs, but a number of studies of various immune response genes are now being performed with a view to identifying genotypes associated with rejection and/or infection. The key role of cytokines in the immune response and other processes, including fibrosis, has concentrated most of this attention on polymorphisms in cytokine genes. Data on polymorphisms in genes encoding tumor necrosis factor-alpha, transforming growth factor-beta, interferon-gamma and interleukin (IL)-1, 4, 6 and 10 together with the IL-4 receptor have been analyzed but so far there is currently no indication of any consistently positive associations between graft rejection and any of these polymorphisms. Studies of other immunomodulatory genes including the CTLA4 gene and the chemokine receptor CCR-5 have proved more positive though the data, so far, are only preliminary. In conclusion, additional large series studies of these and other cytokine genes, as well as other immunoregulatory gene polymorphisms of proven functional significance are needed to achieve major progress in this area.  N. Ref:: 112

 

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[83]

TÍTULO / TITLE:  - Neoral monitoring 2 hours post-dose and the pediatric transplant patient.

REVISTA / JOURNAL:  - Pediatr Transplant 2003 Feb;7(1):25-30.

AUTORES / AUTHORS:  - Dunn SP

INSTITUCIÓN / INSTITUTION:  - Alfred I. duPont Hospital for Children, Wilmington, Delaware 19899, USA. Sdunn@nemours.org

RESUMEN / SUMMARY:  - Cyclosporin A therapy has evolved greatly over the past 25 years of clinical experience. Sophisticated studies of CsA pharmacokinetics and pharmacodynamics have led to a better understanding of the relationship between dose response and biological effect. It has become apparent that achieving target drug exposure is necessary for optimal clinical outcomes. Monitoring dose response has become a key aspect of immunosuppressive management. This review presents the information available supporting cyclosporin drug concentration drawn two hours post dose (C-2) in children who have been transplanted as the best single indicator of CsA exposure. Further studies evaluating the clinical benefit of achieving C-2 targets in children are indicated.  N. Ref:: 30

 

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[84]

TÍTULO / TITLE:  - Apoptosis, TGF beta and transfusion-related immunosuppression: Biologic versus clinical effects.

REVISTA / JOURNAL:  - Transfus Apheresis Sci 2003 Oct;29(2):127-9.

AUTORES / AUTHORS:  - Dzik WH

INSTITUCIÓN / INSTITUTION:  - Blood Transfusion Service, J-224, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. sdzik@partners.org

RESUMEN / SUMMARY:  - Whether or not blood transfusion exerts an immunosuppressive effect on the recipient remains an area of controversy. The mechanism to clearly explain the effect has been elusive. We have previously suggested that there may be two categories of immunosuppressive transfusion effect: one which is HLA-dependent and directed against adaptive immunity and a second category which is mild, non-specific, and directed against innate immunity. This non-specific effect might result from the infusion of apoptotic blood cells. There is solid evidence that blood cells undergo apoptotic changes during refrigerated storage. The infusion of apoptotic cells has recently been shown in animal models to be immunosuppressive. Immunosuppression resulting from the infusion of apoptotic cells may be linked to transforming growth factor beta (TGF-beta).  N. Ref:: 10

 

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[85]

TÍTULO / TITLE:  - Pyogenic granuloma in a renal transplant patient: case report.

REVISTA / JOURNAL:  - Spec Care Dentist 2001 Sep-Oct;21(5):187-90.

AUTORES / AUTHORS:  - al-Zayer M; da Fonseca M; Ship JA

INSTITUCIÓN / INSTITUTION:  - Department of Orthodontics and Pediatric Dentistry, University of Michigan School of Dentistry, 1011 N. University Ave., Ann Arbor, MI 48109, USA.

RESUMEN / SUMMARY:  - This case report describes a 14-year-old female referred to Pediatric Dentistry for evaluation and treatment of cyclosporine-induced gingival hyperplasia. Examination of the anterior maxillary area showed a red, vascular, exophytic, soft-tissue mass which had been excised a few months earlier without a histopathologic examination being done. The mass did not appear consistent with gingival overgrowth induced by long-term use of medication, and thus an excisional biopsy was performed, which diagnosed the lesion as a pyogenic granuloma. A review of the literature and management recommendations are discussed.  N. Ref:: 20

 

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[86]

TÍTULO / TITLE:  - Annual trends and triple therapy--1991-2000.

REVISTA / JOURNAL:  - Clin Transpl 2001;:247-69.

AUTORES / AUTHORS:  - Nishikawa K; Terasaki PI

INSTITUCIÓN / INSTITUTION:  - Terasaki Foundation Laboratory, Los Angeles, CA, USA.

RESUMEN / SUMMARY:  - 1. Although the number of cadaver donor transplants did not increase substantially over the past 10 years, unrelated living donor grafts increased from 153 in 1991 to 1,661 through 2000. Use of spousal and other unrelated donor organs contributed to this increase. There was a modest increase in living-related donor transplants from 2,328 in 1991 to 3,451 in 2000. 2. Cadaver donor graft survival at one year improved from 84% in 1991 to 90% in 2000. In contrast, one-year graft survival of living donor transplants only improved from 93% in 1991 to 95% in 2000. 3. Throughout the 10-year period, approximately 13% of transplants were repeat transplants from cadaver donors and roughly 8% were regrafts from live donors. 4. Cadaver donor transplants into White recipients declined from 68% in 1991 to 60% in 2000. For living donors, the percentage of White patients remained constant at about 70%. 5. Graft survival in patients of all races was about equal at one year but diverged at 3 years, with Asians having the highest and Blacks having the lowest 3-year graft survival rates. 6. Average donor age increased from 31.7 in 1991 to 36 in 2000 for cadaveric donor transplants and 37.9 in 1991 to 40.4 in 2000 for living donor transplants. Cadaveric kidneys from donors older than 50 years of age yielded significantly lower 3-year graft survival. 7. Average recipient age for cadaveric donor transplants increased from 42.1 in 1991 to 46.8 in 2000. The average recipient age for living donor transplants also increased steadily from 33.7 in 1991 to 42.9 in 2000. There was relatively little effect on graft survival rates for advanced age recipients. 8. The percentage of sensitized recipients receiving cadaver donor grafts declined from 27% in 1991 to 21% in 2000. Similarly, sensitized recipients receiving living donor grafts decreased from 17% in 1991 to 13% in 2000. Graft survival in patients with more than 50% PRA was lower at 3 years for patients receiving cadaveric donor grafts. Highly sensitized patients receiving living donor grafts had graft survival rates similar to those who were not sensitized. 9. Cold ischemia times decreased from an average of 24.2 hours in 1991 to 18.9 hours in 2000. Improved graft survival rates over those 10 years were noted in all groups, and even cold ischemia times more than 36 hours yielded 3-year graft survivals comparable to those with lower cold ischemia times in 1998. 10. The need for dialysis has remained constant at about 23% over the last 10 years for patients receiving kidneys from cadaveric donors. The rate of dialysis for patients receiving kidneys from living donors was about 5% for each of the 10 years examined. First day anuria increased from 11% in 1991 to 16% in 2000 for cadaver donor transplants and 3% in 1999 to 5% in 2000 for living donor grafts. 11. Cadaveric donor patients requiring dialysis had a 3-year graft survival rate of 63% if there was no first day anuria and 56% if they had first day anuria. This is in contrast to 80% 3-year graft survival for those with immediate diuresis and no need for dialysis. The 3-year graft survival rate for those receiving living donor grafts and needing dialysis was 58% if they had first day diuresis and 41% if they ware anuric on the first day. Conversely, those who had first day function and did not require dialysis had 89% 3-year graft survival. 12. Among the patients receiving cadaveric grafts with first day diuresis there was a marked reduction in those with rejection, from 21% in 1991 to 5% in 2000. Similarly, for this type of patient receiving living donor grafts, the reduction was 17% in 1991 to 5% in 2000. However, graft survival among these patients did not change significantly. The greatest improvement was noted in those with first day anuria and no rejection. 13. Patients who did not require dialysis, and had rejection prior to discharge decreased markedly from 17% in 1991 to 3% in 2000 in those receiving cadaveric grafts and 15% in 1991 to 3.9% in 2000 for those receiving living donors. Graft survival of cadaveric transplants in those needing dialysis, with and without rejection, improved the most in the 10 year period. 14. Hospitalization days for cadaveric transplant recipients were reduced from 19 days in 1991 to 10 days in 2000 and 16 days in 1991 to 8 days in 2000 for recipients of living donor grafts. There was an increase in discharge serum creatinine values from 2.3 mg/dl in 1991 to 3.3 mg/dl in 2000 for cadaver donor grafts. 15. Double therapy was utilized for about 15% of cadaveric and living donors. There was a sharp increase in induction therapy, peaking at 51% in 1994 and decreasing to 5% by 2000 for cadaveric donor transplants. Induction did not improve graft survival for either cadaver or living donor transplant recipients. 16. Triple therapy improved graft survival of White and Black patients, but did not affect the half-lives in either race. 17. The lower graft survival from older donors was not affected by triple therapy for cadaver donor transplants. Triple therapy removed the donor age effect for recipients of living donor grafts. 18. Triple therapy practically eliminated the effect of sensitization for cadaveric donor grafts. Both double and triple therapy virtually eliminated the sensitization effect for living donors. 19. Triple therapy significantly improved the survival of kidneys with more than 36 hours cold ischemia time so that 3-year graft survival was 76% at 3 years compared with 81% for kidneys stored 1-12 hours. 20. Triple therapy improved the 3-year graft survival of kidneys with first day anuria from 50% for double therapy to 69% for triple therapy in cadaver donor transplants. For living donor transplants, there was a similar improvement from 57% with double therapy to 72% with triple therapy. 21. Triple therapy improved the 3-year cadaveric graft survival rate of kidneys requiring dialysis from 51% with double therapy to 67% for triple therapy. There was a similar improvement for living donors needing dialysis from 37% to 61% at 3 years.

 

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[87]

TÍTULO / TITLE:  - Superficial leiomyosarcoma of the head and neck: case report and review of the literature.

REVISTA / JOURNAL:  - Ear Nose Throat J 2001 Jul;80(7):449-53.

AUTORES / AUTHORS:  - Snowden RT; Osborn FD; Wong FS; Sebelik ME

INSTITUCIÓN / INSTITUTION:  - Department of Otolaryngology-Head and Neck Surgery, University of Tennessee, 956 Court Ave., B219, Memphis, TN 38163, USA. tsnowden@utmem.edu

RESUMEN / SUMMARY:  - Superficial leiomyosarcomas are rare in the head and neck region. Because of the infrequent nature of soft tissue sarcomas in general, superficial leiomyosarcomas are often misdiagnosed on clinical grounds. Immunohistochemistry is essential for an accurate histologic diagnosis, and it should include a broad panel of antibody studies. With respect to differences in clinical appearance and biologic behavior, superficial leiomyosarcomas can be broadly classified as either cutaneous or subcutaneous; local control and overall survival are significantly more favorable in patients with the former. The primary treatment of a leiomyosarcoma is a wide surgical excision with an emphasis on negative margins. Treatment failures are usually attributable to a local recurrence. Systemic metastasis occurs in about one-third of patients with subcutaneous involvement. Although cutaneous leiomyosarcoma is considered a relatively more benign process with minimal metastatic potential, systemic metastasis is still possible. This was demonstrated in our case, as a recurrent cutaneous leiomyosarcoma metastasized to the lung. Proper management requires inclusion of this entity in the differential diagnosis, as well as familiarity with its clinical behavior. In this article, we review the literature on superficial leiomyosarcoma and discuss its epidemiology, presentation, clinical behavior, evaluation, tissue diagnosis, staging, and treatment.  N. Ref:: 24

 

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[88]

TÍTULO / TITLE:  - Chronic urticaria: a role for newer immunomodulatory drugs?

REVISTA / JOURNAL:  - Am J Clin Dermatol 2003;4(5):297-305.

AUTORES / AUTHORS:  - Tedeschi A; Airaghi L; Lorini M; Asero R

INSTITUCIÓN / INSTITUTION:  - Allergy and Immunopharmacology Unit, First Division of Internal Medicine, IRCCS Ospedale Maggiore Policlinico, Milan, Italy. aval.ted@tin.it

RESUMEN / SUMMARY:  - Chronic urticaria is now recognized as an autoreactive disorder in a substantial fraction of patients. A serologic mediator of whealing has been demonstrated in 50-60% of patients with chronic urticaria, and autoantibodies against the high affinity IgE receptor or IgE have been detected in about half of these patients. The demonstration that chronic urticaria is frequently autoimmune has encouraged a more aggressive therapeutic approach, with the use of immunomodulatory drugs.A step-by-step approach to the management of chronic urticaria is proposed, based on our personal experience and review of current medical literature, identified through Medline research and hand searching in medical journals.The non- or low-sedating H(1) receptor antagonists (antihistamines), such as cetirizine, fexofenadine, loratadine, mizolastine and, more recently, levocetirizine, desloratadine and ebastine, represent the basic therapy for all chronic urticaria patients. Older sedating antihistamines, such as hydroxyzine and diphenhydramine, may be indicated if symptoms are severe, are associated with angioedema, and if the patient is anxious and disturbed at night.Corticosteroid therapy with prednisone or methylprednisolone can be administered for a few days (7-14) if urticarial symptoms are not controlled by antihistamines and a rapid clinical response is needed. In cases of relapse after corticosteroid suspension, leukotriene receptor antagonists, such as montelukast and zafirlukast, should be tried. In our experience, remission of urticarial symptoms can be achieved in 20-50% of chronic urticaria patients unresponsive to antihistamines alone. When urticaria is unremitting and is not controlled by combined therapy with antihistamines and leukotriene receptor antagonists, prolonged corticosteroid therapy may be needed. Long-term corticosteroid therapy should be administered at the lowest dose able to control urticarial symptoms, in order to minimize adverse effects. In a few patients, however, high-dose corticosteroid therapy may have to be administered for long periods. In these patients, immunosuppressive treatment with low-dose cyclosporine can be started. This type of treatment has a corticosteroid-sparing effect and is also generally effective in patients with severe, unremitting urticaria, but requires careful monitoring of cyclosporine plasma concentration and possible adverse effects.Other immunomodulating drugs that have been tried in chronic urticaria patients include hydroxychloroquine, dapsone, sulfasalazine and methotrexate, but their efficacy has not been proven in large controlled studies. Warfarin therapy may also be considered in some patients with chronic urticaria and angioedema unresponsive to antihistamines.  N. Ref:: 91

 

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[89]

TÍTULO / TITLE:  - Diagnosis and management of aplastic anemia and myelodysplastic syndrome.

REVISTA / JOURNAL:  - Oncology (Huntingt) 2002 Sep;16(9 Suppl 10):153-61.

AUTORES / AUTHORS:  - Paquette RL

INSTITUCIÓN / INSTITUTION:  - Division of Hematology/Oncology, University of California at Los Angeles, 90095-1678, USA. paquette@ucla.edu

RESUMEN / SUMMARY:  - The bone marrow failure states, aplastic anemia and myelodysplastic syndrome, are characterized by reticulocytopenic anemia, with variable neutropenia and thrombocytopenia. The bone marrow biopsy is very hypocellular in aplastic anemia, but it is usually hypercellular in myelodysplastic syndrome. Marrow cytogenetic abnormalities are present in approximately half of myelodysplastic syndrome patients but are absent in aplastic anemia. Allogeneic bone marrow transplantation is the treatment of choice for young patients with severe aplastic anemia. Immunosuppressive therapy with antithymocyte globulin (ATG) and cyclosporine is used when transplantation is not the initial therapeutic choice; it induces responses in 65% to 80% of patients. Treatment of myelodysplastic syndrome is dependent upon risk classification, and patient age and performance status. Allogeneic stem cell transplantation should be considered for younger myelodysplastic syndrome patients. An acute myelogenous leukemia (AML) type of induction chemotherapy may benefit high-risk patients with a good performance status for whom allogeneic transplantation is not an option. Patients achieving a complete remission to induction chemotherapy may be considered for autologous stem cell transplantation. However, aggressive therapy is an option for only a minority of myelodysplastic syndrome patients; most receive supportive care. Anemia, and its related symptoms, is the principal problem for most myelodysplastic syndrome patients. Erythropoietin administration ameliorates anemia in a minority of myelodysplastic syndrome patients. A wide variety of novel experimental approaches including immunosuppressive therapy, angiogenesis inhibitors, platelet growth factors, and demethylating agents are now under investigation for myelodysplastic syndrome.  N. Ref:: 53

 

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[90]

TÍTULO / TITLE:  - Autoimmune haemolytic anaemia in a newborn infant.

REVISTA / JOURNAL:  - Arch Dis Child Fetal Neonatal Ed 2003 Jul;88(4):F341-2.

AUTORES / AUTHORS:  - Motta M; Cavazza A; Migliori C; Chirico G

INSTITUCIÓN / INSTITUTION:  - Division of Neonatology and Neonatal Intensive Care, Spedali Civili, Brescia, Italy.

RESUMEN / SUMMARY:  - The case is reported of an infant with autoimmune haemolytic anaemia of perinatal onset. Combined treatment with steroids and cyclosporin was necessary to improve haemolysis and reduce the high transfusion requirements. Treatment was discontinued at 13 months of age. The child was healthy at the follow up at 24 and 36 months of age.  N. Ref:: 10

 

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[91]

TÍTULO / TITLE:  - Cutaneous lupus erythematosus: diagnosis and management.

REVISTA / JOURNAL:  - Am J Clin Dermatol 2003;4(7):449-65.

AUTORES / AUTHORS:  - Fabbri P; Cardinali C; Giomi B; Caproni M

INSTITUCIÓN / INSTITUTION:  - Department of Dermatological Sciences, University of Florence, Florence, Italy. fabbri@unifi.it

RESUMEN / SUMMARY:  - Cutaneous lupus erythematosus (CLE) includes a variety of lupus erythematosus (LE)-specific skin lesions that are subdivided into three categories - chronic CLE (CCLE), subacute CLE (SCLE) and acute CLE (ACLE) - based on clinical morphology, average duration of skin lesions and routine histopathologic examination. This paper describes our personal experience in the management of CLE over the last 30 years, with details on preferential therapeutic options related to clinical, histologic and immunopathologic aspects of each clinical subset of the disease. Effective sunscreening and sun protection are considered the first rule in the management of CLE because of the high degree of photosensitivity of the disease. Antimalarial agents are crucial in the treatment of CLE and are the first-line systemic agents, particularly in discoid LE (DLE) and SCLE. Dapsone is the drug of choice for bullous systemic LE (BSLE) as well as for LE in small dermal vessels (e.g. leukocytoclastic vasculitis). Retinoids, known as second-line drugs for systemic therapy, are sometimes used to treat chronic forms of CLE and are particularly successful in treating hypertrophic LE. Systemic immunosuppressive agents are required to manage the underlying systemic LE disease activity in patients with ACLE. These drugs, especially azathioprine, methotrexate, cyclophosphamide and cyclosporine, together with corticosteroids, constitute third-line systemic therapy of CLE. In our experience, oral prednisone or parenteral ‘pulsed’ methylprednisolone are useful in exacerbations of disease activity. Thalidomide provides one of the most useful therapeutic alternatives for chronic refractory DLE, although its distribution is limited to a few countries because of the risk of teratogenicity and polyneuropathy. However, medical treatment with local corticosteroids remains the mainstay of CLE treatment, especially for DLE. Patient education regarding the disease is also important in the management of CLE, because it helps relieve undue anxiety and to recruit the patient as an active participant in the treatment regimen.  N. Ref:: 113

 

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[92]

TÍTULO / TITLE:  - The role of immunosuppression in lymphoma.

REVISTA / JOURNAL:  - Recent Results Cancer Res 2002;159:55-66.

AUTORES / AUTHORS:  - Trofe J; Buell JF; First MR; Hanaway MJ; Beebe TM; Woodle ES

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, University of Cincinnati, OH 45267-0558, USA.

RESUMEN / SUMMARY:  - Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized yet serious complication in solid organ transplant recipients and currently represents the second most common de novo malignancy following solid organ transplantation. PTLD has been noted in all transplant immunosuppressive eras including the pre-cyclosporine, cyclosporine, and post-cyclosporine eras. The time from organ transplantation to PTLD presentation varies widely from less than 1 month to several years. PTLD presents with a broad spectrum of clinical manifestations depending on the transplanted organ, immunosuppressive therapy and patient age. Intense immunosuppressive therapy is a major risk factor for development of PTLD. Whenever a new agent is introduced, there is a learning curve that leads to dosing modifications, which in turn result in optimization of its immunosuppressive efficacy and reduction of toxicities, including PTLD. We review the major historical and recent immunosuppression trials to assess the impact of individual immunosuppressive agents and regimens on PTLD risk.  N. Ref:: 34

 

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[93]

TÍTULO / TITLE:  - Severe aplastic anemia and allogeneic hematopoietic stem cell transplantation.

REVISTA / JOURNAL:  - AACN Clin Issues 2002 May;13(2):169-91.

AUTORES / AUTHORS:  - Myer SA; Oliva J

INSTITUCIÓN / INSTITUTION:  - Department of Nursing, State University of New York at Brockport, NY 14420, USA. smyer@brockport.edu

RESUMEN / SUMMARY:  - Aplastic anemia is a form of bone marrow failure that ranges in severity from mild to severe. In all cases, some degree of pancytopenia is present. The cause usually is unknown, although many drugs and viruses are associated with the disease. The pathophysiology of aplastic anemia involves either a stem cell defect or injury or an immunologically mediated hematopoietic cell destruction, which may operate in concert with abnormalities in programmed cell death. Excellent clinical care and research have dramatically improved patient survival, with 70% to 90% of sibling hematopoietic stem cell transplant recipients surviving long term. Patients with mild or moderate disease may not require immediate treatment. If and when these patients require treatment, the mainstay of therapy is immunosuppression. The initial drug regimen includes antithymocyte globulin, often in combination with cyclosporine A, followed by moderate-dose steroids and cyclophosphamide. Nurses assess and monitor patients and their progress, recognizing medication adverse effects. Nurses educate patients about their disease and its treatment, and provide necessary emotional support. Severe aplastic anemia is treated with allogeneic hematopoietic stem cell transplantation. This therapy involves complex nursing challenges. The patient goes through an extensive pretransplantation workup. Donor selection and harvesting of hematopoietic stem cells are preludes to an intensive preparative regimen. This preparative or conditioning regimen and the need for long-term immunosuppression are the reasons for many of the acute complications and adverse events that may follow the hematopoietic stem cell transplantation. Nurses must be vigilant in assessing and monitoring patients for toxicities and long-term complications that may affect almost any organ system.  N. Ref:: 86

 

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[94]

TÍTULO / TITLE:  - Maintenance immunosuppression.

REVISTA / JOURNAL:  - Clin Transpl 2001;:223-36.

AUTORES / AUTHORS:  - Takemoto SK

RESUMEN / SUMMARY:  - An “intent-to-treat” analysis was developed to examine the administration of primary and adjunctive immunosuppressive agents by year of transplant for unsensitized, sensitized, multi-organ and living donor transplant recipients by centers reporting to the UNOS Registry of Renal Transplant Recipients. Based on these analyses, several trends were noted: Tacrolimus became the dominant primary agent for multi-organ transplant recipients in 1998, sensitized recipients in 2000, and unsensitized and living-donor transplant recipients in 2001. MMF became the dominant adjunctive agent for all transplants studied in 1996. The combination of CsA-MMF was most often administered to unsensitized and living donor recipients while Tac-MMF was most often used for multi-organ transplants. The trend of decreasing rejection rates from 60% in 1996 to 20% in 2001 was similar for each type of transplant studied. Rejection rates were highest with the Csa-Aza combination and lowest with the Tac-MMF combination. Combinations with the lowest rates of rejection did not necessarily have the highest graft outcome. HLA matching decreased rejection rates and improved graft outcome for each type of transplant and immunosuppression combination. Graft outcome in HLA-matched living donor transplants was highest with the less potent CsA-Aza combination and lowest with the Tac-MMF combination. Treatment crossover from CsA to Tac or Aza to MMF was least frequent among HLA-matched recipients. Crossover from MMF to Aza was highest in HLA-matched living donor transplants.

 

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[95]

TÍTULO / TITLE:  - Psoriasis in children: a guide to its diagnosis and management.

REVISTA / JOURNAL:  - Paediatr Drugs 2001;3(9):673-80.

AUTORES / AUTHORS:  - Leman J; Burden D

INSTITUCIÓN / INSTITUTION:  - Department of Dermatology, Western Infirmary, Glasgow, Scotland.

RESUMEN / SUMMARY:  - Psoriasis often presents in childhood. The diagnosis may be challenging if the disease is mild or the presentation is atypical. All of the forms recognised in adults are encountered in childhood (plaque, guttate, erythrodermic and pustular). Guttate and flexural forms are particularly common in children. Successful management requires education of the child and parents regarding the course of the disease and treatment options. Environmental triggers should be sought out and eliminated where possible. Most patients respond to topical treatment with emollients, coal tar, anthralin (dithranol) or calcipotriol. Treatment is tailored according to patient age, extent and distibution of psoriasis. For those who fail to respond, daycare or inpatient care is appropriate. Phototherapy with UVB may be combined with topical agents. Systemic therapy is required in a minority, usually those with resistant or erythrodermic disease, pustular psoriasis and arthropathic psoriasis. Retinoids are probably the systemic agent of choice. There are few data regarding the use of methotrexate or cyclosporin in childhood psoriais.  N. Ref:: 55

 

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[96]

TÍTULO / TITLE:  - New monoclonal antibodies in renal transplantation.

REVISTA / JOURNAL:  - Minerva Urol Nefrol 2003 Mar;55(1):57-66.

AUTORES / AUTHORS:  - Vincenti F

INSTITUCIÓN / INSTITUTION:  - Kidney Transplant Service, University of California, San Francisco, CA 94143-0780, USA. vincentif@surgery.ucsf.edu

RESUMEN / SUMMARY:  - A decade of spectacular innovation in maintenance immunosuppression drugs has resulted in dramatic reductions in acute rejection and improvement in short and long term outcome after renal transplantation. However the new drugs continue to lack specificity, many require frequent therapeutic drug monitoring and all are associated with acute and chronic toxicities. The new biologic agents, monoclonal antibodies (chimeric, humanized, and fully human) and receptor-fusion proteins, lack immunogenicity, have long half-life and prolonged biologic effects, require intermittent administration and have minimal toxicity. The specificity and selectively of the targets of the new biologic agents render them less toxic than the oral maintenance drugs and thus could possibly replace the maintenance drugs most associated with long-term toxicity such as the corticosteroids and the calcineurin inhibitors. The recently introduced anti-interleukin 2 receptor (IL-2R) monoclonal antibodies (mAbs) are the prototype of future biologic agents; selective, safe, and inducing prolonged biologic effects. The IL-2R mAbs have been used with a variety of maintenance immunosuppression regimens double therapy with cyclosporine and prednisone, triple therapy with cyclosporine, azathioprine and prednisone and with newer regimens such as cyclosporine or tacrolimus, mycophenolate mofetil (MMF) and prednisone, and most recently with sirolimus, MMF and prednisone. The major thrust of the new biologics in clinical development is to block the co-stimulatory pathway. The first attempt at blockade of the CD40-CD154 with anti-CD154 mAbs was disappointing. Anti-CD 154 therapy was associated with thromboembolic events and acute rejection. Attempts at blocking the CD28-B7s (CD80-CD86) pathway are currently underway with the receptor fusion protein, LEA29Y a second generation CTL4Aig, and humanized mAbs to CD 80 and CD86. LFA1, an adhesion molecule that also participates in the co-stimulatory pathway, has also been targeted with a mAb that binds to the CD11a chain of LFA1. Efalizumab, a humanized anti-CD11a mAb, was shown in a phase I trial to be potentially effective in renal transplantation. A humanized anti-CD45 RB mAb is currently in pre-clinical studies and will likely be tested in a phase I trial of renal transplantation within 1 year. While excellent results with anti-CD45 RB mAbs have been published in experimental transplantation, the mechanism of action of anti-CD45 RB mAbs remains to be determined. Several antibodies that are currently approved for non-transplant indications are currently used in single center clinical trials in renal transplantation including Campath 1 H, a humanized anti-CD52 mAb, Rituxamab, an anti-CD20 chimeric mAb, and Infliximab an anti-TNFa chimeric mAb. In addition, several humanized mutagenized anti-CD3 mAbs, huOKT3g1, aglycosyl CD3 and HuM291 have been used in limited trials in renal transplantation but have yet to have a formal clinical development. Humanized mAbs and receptor fusion proteins offer the potential of providing renal transplant recipients with a novel algorithm for immunosuppression that relies on chronic intermittent intravenous administration of safe, non-toxic agents replacing oral drug therapy maintenance.  N. Ref:: 50

 

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[97]

TÍTULO / TITLE:  - An update in transplant immunosuppressive therapy.

REVISTA / JOURNAL:  - Med Health R I 2002 Apr;85(4):131-3.

AUTORES / AUTHORS:  - Thursby MA; Yango AF; Gohh RY

INSTITUCIÓN / INSTITUTION:  - Rhode Island Hospital, Division of Renal Diseases, 593 Eddy Street, Providence, RI 02903, USA. Mthursby@lifespan.org  N. Ref:: 10

 

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[98]

TÍTULO / TITLE:  - Protocol biopsy and subclinical rejection in patients after kidney transplantation treated by tacrolimus (Prograf).

REVISTA / JOURNAL:  - Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2003 Dec;147(2):193-6.

AUTORES / AUTHORS:  - Zadrazil J; Krejci K; Al-Jabry S; Horcicka V Jr; Tichy T; Hrabalova M; Bachleda P

INSTITUCIÓN / INSTITUTION:  - 3rd Clinic of Internal Medicine, Teaching Hospital, I. P. Pavlova 22, Olomouc, 775 00, Czech Republic.

RESUMEN / SUMMARY:  - The article deals with the contribution of tacrolimus (Prograf) to improvement in kidney transplant results. Tacro-limus, in comparison with cyclosporine significantly reduces the incidence of acute rejection and improves survival of grafts as well as patients. Based on the literature, the primary immunological differences between tacrolimus and cyclosporine effects are pointed out. These differences explain the better immunosuppressive effectiveness of tacrolimus. Based on analysis of the results, subclinical rejection problems and significance of protocol biopsy for present-day transplantology are discussed. There is also a critical analysis of the questions, which priority, in relationship to the expanding availability of immunosuppressive substances currently has high interest for nephrologists researching subclinical rejection.

 

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[99]

TÍTULO / TITLE:  - Immunosuppression in liver transplantation.

REVISTA / JOURNAL:  - Minerva Chir 2003 Oct;58(5):725-40.

AUTORES / AUTHORS:  - Everson GT; Trotter JF; Kugelmas M; Forman L

INSTITUCIÓN / INSTITUTION:  - Division of Gastroenterology and Hepatology and Department of Medicine, University of Colorado School of Medicine, Denver, CO 80262, USA. greg.overson@uchsc.edu

RESUMEN / SUMMARY:  - This article highlights the currently available immunosuppressive medications that are used to prevent or treat hepatic allograft rejection. Currently-available immunosuppressive medications are highly effective in prevention of allograft rejection, graft loss, and patient death. However, side effects of medications are common, usually dose-related, and specific to the administered drug. Maintenance immunosuppression which has been primarily based upon calcineurin inhibitors (Cyclosporine, CsA, or tacrolimus, Tac) is commonly modified to reduce metabolic complications of therapy. Toxic consequences of steroids may be ameliorated by steroid withdrawal without risk of acute rejection or immunologic graft loss. Calcineurin-sparing regimens may include use of mycophenolate mofetil (MMF) or sirolimus, and allow reduction in doses and plasma levels of CsA and Tac. Recurrence of hepatitis C is universal after liver transplantation and progresses rapidly, compared to its natural history in non-immunocompromised patients. Unfortunately, no single immunosuppressive agent or strategy has yet been shown to convincingly modify the course of post-transplant recurrence. Most centers manage recurrenc hepatitis C by either steroid avoidance, reduction in immunosuppression, or institution of antiviral therapy. Ongoing advances in immunosuppressive and antiviral medications will allow tailoring of the immunosuppressive prescription, which undoubtedly will benefit current and future liver recipients.  N. Ref:: 88

 

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[100]

TÍTULO / TITLE:  - The management of immunosuppression: the art and the science.

REVISTA / JOURNAL:  - Crit Care Nurs Q 2004 Jan-Mar;27(1):61-4.

AUTORES / AUTHORS:  - Mancini MC; Cush EM; Launius BK; Brown PA

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Louisiana State University Health Sciences Center, Shreveport, La, USA.

RESUMEN / SUMMARY:  - The optimal use of immunosuppressant drugs requires an understanding of their mechanism of action as well as a basic understanding of the biology of transplant rejection and tolerance. The ability to tailor a drug regimen that strikes a fine balance between allograft maintenance and patient well-being demands a sensitivity to the patient’s needs and expectations as well. The object of this article is to cover the basic biological principles involved in selecting an immunosuppressant protocol while sharing our experiences with these various regimen.  N. Ref:: 19

 

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[101]

TÍTULO / TITLE:  - Kidney transplantation from living donors: comparison of results between related and unrelated donor transplants under new immunosuppressive protocols.

REVISTA / JOURNAL:  - Isr Med Assoc J 2003 Sep;5(9):622-5.

AUTORES / AUTHORS:  - Chkhotua AB; Klein T; Shabtai EL; Yussim A; Bar-Nathan N; Shaharabani E; Lustig S; Mor E

INSTITUCIÓN / INSTITUTION:  - National Center of Urology, Tbilisi, Georgia.

RESUMEN / SUMMARY:  - BACKGROUND: Recent advances in immunosuppressive therapy have led to a substantial improvement in the outcome of kidney transplantation. Living unrelated donors may become a source of additional organs for patients on the kidney waiting list. OBJECTIVES: To study the impact of the combination of calcineurin inhibitors and mycophenolate-mofetile, together with steroids, on outcomes of living related and unrelated transplants. METHODS: Between September 1997 and January 2000, 129 patients underwent living related (n = 80) or unrelated (n = 49) kidney transplant. The mean follow-up was 28.2 months. Immunosuppressive protocols consisted of MMF with cyclosporine (41%) or tacrolimus (59%), plus steroids. Patient and graft survival data, rejection rate, and graft functional parameters were compared between the groups. RESULTS: LUD recipients were older (47.8 vs. 33.6 years) with a higher number of re-transplants (24.5% vs. 11.2% in LRD recipients, P < 0.05). Human leukocyte antigen matching was higher in LRD recipients (P < 0.001). Acute rejection developed in 28.6% of LUD and 27.5% of LRD transplants (P = NS). Creatinine levels at 1, 2 and 3 years post-transplant were 1.6, 1.7 and 1.7 mg/dl for LRD patients and 1.5, 1.5 and 1.3 mg/dl for LUD recipients (P = NS). There was no difference in patient survival rates between the groups. One, 2 and 3 years graft survival rates were similar in LRD (91.3%, 90% and 87.5%) and LUD (89.8%, 87.8% and 87.8%) recipients. CONCLUSIONS: Despite HLA disparity, rejection and survival rates of living unrelated transplants under current immunosuppressive protocols are comparable to those of living related transplants.

 

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[102]

TÍTULO / TITLE:  - Evolution of biologic therapies for the treatment of psoriasis.

REVISTA / JOURNAL:  - Skinmed 2003 Sep-Oct;2(5):286-94.

AUTORES / AUTHORS:  - Gordon KB; McCormick TS

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, Division of Dermatology, Loyola University, Stritch School of Medicine, Maywood, IL 60153, USA. kgordon@lumc.edu

RESUMEN / SUMMARY:  - Over the past three decades, laboratory and clinical research findings have shown that T cells are the primary mediators of psoriasis pathogenesis and that psoriasis can be treated by eliminating these T cells or interfering with their activation or activity. Based on these observations, many new biologic therapies to treat psoriasis are now in development. These agents, developed primarily through recombinant DNA techniques, are designed to target T cells and the immunologic cascade associated with their activation. Four basic strategic approaches that focus on the steps involved in the immunopathology of psoriasis are: 1) elimination of the pathogenic T cells; 2) inhibition of T-cell activation, proliferation, and migration; 3) immune deviation to down-regulate the type 1 (TH1) response predominant in psoriasis; and 4) blockade of cytokine production. The goal of these new therapies is to improve the treatment of psoriasis, particularly moderate to severe disease, with agents that are well tolerated and safe for long-term use.  N. Ref:: 52

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