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

 

INMUNOSUPRESIÓN *** IMMUNOSUPPRESSION

(Conceptos / Keywords: Immunosuppression; Immunosuppressive ag.; Transpl. immunol.; GVH; Antirejection therapy; Lymphocyte depletion; Transpl. conditioning; etc).

 

Enero / January 2001 --- Marzo / March 2004

 

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Enlace / Link

 

[1]

TÍTULO / TITLE:  - Impact of shared epitope genotype and ethnicity on erosive disease: a meta-analysis of 3,240 rheumatoid arthritis patients.

REVISTA / JOURNAL:  - Arthritis Rheum 2004 Feb;50(2):400-12.

      ●● Enlace al texto completo (gratuito o de pago) 1002/art.20006

AUTORES / AUTHORS:  - Gorman JD; Lum RF; Chen JJ; Suarez-Almazor ME; Thomson G; Criswell LA

INSTITUCIÓN / INSTITUTION:  - University of California, San Francisco, CA 94143-0500, USA. lac@itsa.ucsf.edu

RESUMEN / SUMMARY:  - OBJECTIVE: The strongest known genetic association in rheumatoid arthritis (RA) is with HLA-DRB1 alleles that share a similar amino acid sequence, termed the shared epitope (SE). Although many studies have examined the association of the SE with disease severity, the results have been inconsistent, which may reflect the relatively small sample sizes or ethnic differences. The aim of this study was to assess the association of HLA-DRB1 SE alleles and genotype with the development of bony erosions in RA by meta-analysis. METHODS: We identified English-language articles published between January 1, 1987 and June 1, 1999 through Medline, EMBase, and manual searches of 6 relevant journals. Included were studies in which molecular typing of HLA-DRB1 alleles was performed and in which the presence or absence of bony erosions was reported. Data were extracted from the studies, and erosions were coded as present or absent. Authors were contacted for missing information and data on individual patients. RESULTS: A total of 29 studies and 3,240 patients were available for analysis. The summary odds ratios (ORs), when all patients were evaluated as a single group, demonstrated a significant association of the presence of the SE (2 or 1 versus 0 SE alleles) with erosions (OR 2.0; 95% confidence interval [95% CI] 1.8-2.2), although significant heterogeneity was present (P = 0.002). Subgroup analyses demonstrated the important influence of ethnic background. For example, no association of the SE with erosions was demonstrated in Greeks (OR 0.8 [95% CI 0.2-1.5]). In contrast, there was a striking dose-dependent relationship in southern European Caucasians and Asians, with ORs as high as 6.2 and 5.4, respectively, in patients with 2 SE alleles. Although our ability to assess the relationship between SE genotype and erosions was limited, particular importance of the DRB1*0401 SE allele was suggested in an analysis restricted to northern European Caucasians. CONCLUSION: The SE is associated with the development of erosive disease in many ethnic groups; however, striking exceptions exist. These variations may be due to allele differences between populations, such as the frequency of DRB1*0401 among different ethnic groups. Further study to better understand the genetic and environmental differences between these populations may provide insight into mechanisms that influence the clinical expression of RA.

 

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[2]

TÍTULO / TITLE:  - Skin cancers after organ transplantation.

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

      ●● Enlace a la Editora de la Revista http://content.nejm.org/ 

      ●● Cita: New England J Medicine (NEJM): <> 2003 Apr 24;348(17):1681-91.

      ●● Enlace al texto completo (gratuito o de pago) 1056/NEJMra022137

AUTORES / AUTHORS:  - Euvrard S; Kanitakis J; Claudy A

INSTITUCIÓN / INSTITUTION:  - Department of Dermatology, Edouard Herriot Hospital, Lyons, France. sylvie.euvrard@numericable.fr  N. Ref:: 100

 

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[3]

TÍTULO / TITLE:  - Interferon-gamma reduces interleukin-4- and interleukin-13-augmented transforming growth factor-beta2 production in human bronchial epithelial cells by targeting Smads.

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

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

      ●● Cita: Chest: <> 2003 Mar;123(3 Suppl):372S-3S.

AUTORES / AUTHORS:  - Wen FQ; Liu XD; Terasaki Y; Fang QH; Kobayashi T; Abe S; Rennard SI

INSTITUCIÓN / INSTITUTION:  - Pulmonary and Critical Care Medicine Section, University of Nebraska Medical Center, Omaha, NE 68198-5125, USA.  N. Ref:: 0

 

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[4]

TÍTULO / TITLE:  - Immune tolerance after long-term enzyme-replacement therapy among patients who have mucopolysaccharidosis I.

REVISTA / JOURNAL:  - Lancet 2003 May 10;361(9369):1608-13.

AUTORES / AUTHORS:  - Kakavanos R; Turner CT; Hopwood JJ; Kakkis ED; Brooks DA

INSTITUCIÓN / INSTITUTION:  - Lysosomal Diseases Research Unit, Department of Chemical Pathology, Women’s and Children’s Hospital, North Adelaide, South Australia, Australia

RESUMEN / SUMMARY:  - BACKGROUND: Enzyme-replacement therapy has been assessed as a treatment for patients who have mucopolysaccharidosis I (alpha-L-iduronidase deficiency). We aimed to investigate the humoral immune response to recombinant human alpha-L-iduronidase among these patients. METHODS: We characterised the antibody titres and specific linear sequence epitope reactivity of serum antibodies to alpha-L-iduronidase for ten patients with mucopolysaccharidosis I, at the start of treatment and after 6, 12, 26, 52, and 104 weeks. We compared the values for patients’ samples with those for samples from normal human controls. FINDINGS: Before enzyme-replacement therapy, all patients had low serum antibody titres to recombinant human alpha-L-iduronidase that were within the control range. Five of the ten patients produced higher-than-normal titres of antibody to the replacement protein during the treatment course (serum antibody titres 130000-500000 and high-affinity epitope reactivity). However, by week 26, antibody reactivity was reduced, and by week 104 all patients had low antibody titres and only low-affinity epitope reactivity. Patients who had mucopolysaccharidosis I with antibody titres within the normal range at 6-12 weeks did not subsequently develop immune responses. INTERPRETATION: After 2 years of treatment, patients who initially had an immune reaction developed immune tolerance to alpha-L-iduronidase. This finding has positive implications for long-term enzyme-replacement therapy in patients who have mucopolysaccharidosis I.  N. Ref:: 32

 

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[5]

TÍTULO / TITLE:  - ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult: Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure): Developed in Collaboration With the International Society for Heart and Lung Transplantation; Endorsed by the Heart Failure Society of America.

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

      ●● Enlace a la Editora de la Revista http://circ.ahajournals.org/ 

      ●● Cita: Circulation: <> 2001 Dec 11;104(24):2996-3007.

AUTORES / AUTHORS:  - Hunt SA; Baker DW; Chin MH; Cinquegrani MP; Feldmanmd AM; Francis GS; Ganiats TG; Goldstein S; Gregoratos G; Jessup ML; Noble RJ; Packer M; Silver MA; Stevenson LW; Gibbons RJ; Antman EM; Alpert JS; Faxon DP; Fuster V; Gregoratos G; Jacobs AK; Hiratzka LF; Russell RO; Smith SC Jr

 

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[6]

TÍTULO / TITLE:  - HLA DNA typing and transplantation.

REVISTA / JOURNAL:  - Immunity 2001 Apr;14(4):347-56.

AUTORES / AUTHORS:  - Erlich HA; Opelz G; Hansen J

INSTITUCIÓN / INSTITUTION:  - Roche Molecular Systems, Alameda, CA 94501, USA. henry.erlich@roche.com  N. Ref:: 26

 

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[7]

TÍTULO / TITLE:  - Fulminant hepatic failure secondary to acetaminophen poisoning: a systematic review and meta-analysis of prognostic criteria determining the need for liver transplantation.

REVISTA / JOURNAL:  - Crit Care Med 2003 Jan;31(1):299-305.

      ●● Enlace al texto completo (gratuito o de pago) 1097/01.CCM.0000034674.51554.4C

AUTORES / AUTHORS:  - Bailey B; Amre DK; Gaudreault P

INSTITUCIÓN / INSTITUTION:  - Division of Emergency Medicine, Department of Pediatrics, Hopital Ste-Justine, Universite de Montreal, Quebec, Canada. baileyb@med.umontreal.ca

RESUMEN / SUMMARY:  - OBJECTIVES: To summarize and compare different prognostic criteria used to determine need for liver transplantation in patients with fulminant hepatic failure secondary to acetaminophen poisoning. DATA SOURCES: Studies published in the literature that investigated criteria for hepatic transplantation secondary to acetaminophen-induced liver failure as identified by a preestablished MEDLINE strategy (1966 through October 2001). STUDY SELECTION: Studies were included if 2 x 2 tables could be reconstructed and if they did not assume that patients undergoing transplantation would have eventually died had they not received the transplant. DATA EXTRACTION: Relevant articles were reviewed by two authors independently. Discrepancies or disagreements, if any, on the inclusion or exclusion of studies were resolved by consulting the third author. DATA SYNTHESIS: King’s criteria (pH < 7.30 or prothrombin time of >100 secs plus creatinine of >300 micromol/L plus encephalopathy grade of > or =3) were evaluated in nine studies, pH < 7.30 in four, prothrombin time of >100 secs in three, prothrombin time of >100 secs plus creatinine of >300 micromol/L plus encephalopathy grade of > or =3 in three, creatinine of >300 micromol/L in two, and one each for increase in prothrombin time day 4, factor V of <10%, Acute Physiology and Chronic Health Evaluation (APACHE) II score of >15, and Gc-globulin of <100 mg/L. King’s criteria were more sensitive than pH: 69% (95% confidence interval, 63-75) vs. 57% (95% confidence interval, 44-68). Their specificities were, however, comparable: 92% (95% confidence interval, 81-97) vs. 89% (95% confidence interval, 62-97). APACHE II score of >15 had the highest positive likelihood ratio (16.4) and the lowest negative likelihood ratio (0.19) but was evaluated in only one study. The accuracy measures of all other criteria were lower than that of King’s criteria or pH < 7.30. CONCLUSIONS: Presently, available criteria are not very sensitive and may miss patients requiring transplantation. Future studies should further evaluate the efficacy of the APACHE II criteria.  N. Ref:: 33

 

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[8]

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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[9]

TÍTULO / TITLE:  - Insulin/IGF and target of rapamycin signaling: a TOR de force in growth control.

REVISTA / JOURNAL:  - Trends Cell Biol 2003 Feb;13(2):79-85.

AUTORES / AUTHORS:  - Oldham S; Hafen E

INSTITUCIÓN / INSTITUTION:  - The Burnham Institute, La Jolla, CA 92037, USA.

RESUMEN / SUMMARY:  - ‘They come in all sizes.’ Apart from its origin and use in the clothing industry, this saying reflects the fact that the size of organisms spans an enormous range. Whether destined to be large or small, species grow in an organized fashion to reach their final specified size. For growth to proceed, food must be metabolized to liberate energy in the form of adenosine triphosphate (ATP) and protein building blocks in the form of amino acids. One major orchestrator of this complex growth process in diverse metazoan species is the insulin/insulin-like growth factor (IGF) system. This review summarizes current studies primarily from Drosophila regarding the function of the insulin/IGF system in the control of growth.  N. Ref:: 75

 

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[10]

TÍTULO / TITLE:  - Diagnosis and therapy of coronary artery disease in renal failure, end-stage renal disease, and renal transplant populations.

REVISTA / JOURNAL:  - Am J Med Sci 2003 Apr;325(4):214-27.

AUTORES / AUTHORS:  - Logar CM; Herzog CA; Beddhu S

INSTITUCIÓN / INSTITUTION:  - Renal Section, Salt Lake VA Healthcare System, Department of Medicine, University of Utah School of Medicine, Salt Lake City, USA.

RESUMEN / SUMMARY:  - Even though cardiovascular disease is the leading cause of death in patients with CRF and end-stage renal disease (ESRD), ill-conceived notions have led to therapeutic nihilism as the predominant strategy in the management of cardiovascular disease in these populations. The recent data clearly support the application of proven interventions in the general population, such as angiotensin-converting enzyme inhibitors and statins to patients with CRF and ESRD. The advances in coronary stents and intracoronary irradiation have decreased the restenosis rates in renal failure patients. Coronary artery bypass with internal mammary graft might be the procedure of choice for coronary revascularization in these patients. The role of screening for asymptomatic coronary disease is established as a pretransplant procedure, but it is unclear whether this will be applicable to all patients with ESRD. Future studies need to focus on unraveling the mechanisms by which uremia leads to increased cardiovascular events to design optimal therapies targeted toward these mechanisms and improve cardiovascular outcomes.  N. Ref:: 125

 

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[11]

TÍTULO / TITLE:  - Individuality: the barrier to optimal immunosuppression.

REVISTA / JOURNAL:  - Nat Rev Immunol 2003 Oct;3(10):831-8.

      ●● Enlace al texto completo (gratuito o de pago) 1038/nri1204

AUTORES / AUTHORS:  - Kahan BD

INSTITUCIÓN / INSTITUTION:  - Division of Immunology and Organ Transplantation, Department of Surgery, University of Texas Medical School at Houston, Suite 6.240, 6431 Fannin, Houston, Texas 77030, USA. Barry.D.Kahan@uth.tmc.edu.

RESUMEN / SUMMARY:  - Immunosuppressive therapy aims to protect transplanted organs from host responses. Individuals have unique repertoires of responses to foreign antigens and toxic reactions to immunosuppressants; the former determining the type or intensity of rejection reactions and the latter influencing the severity of iatrogenic effects. Because existing agents target molecules that are widely distributed in tissues, new strategies must selectively block lymphoid cells only, disrupt alloresponses but not innate immune responses, interact synergistically with other agents, facilitate the homeostatic process that naturally leads to graft acceptance and ideally only interrupt donor-specific responses. Approaches presently under investigation aim to alter cell trafficking, or selectively deviate the maturation of antigen-presenting cells or inhibit lymphocyte-activation cascades - events that are crucial to rejection responses.  N. Ref:: 92

 

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[12]

TÍTULO / TITLE:  - Effect of dexamethasone on beta2-adrenergic desensitization in airway smooth muscle: role of the ARG19 polymorphism.

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

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

      ●● Cita: Chest: <> 2003 Mar;123(3 Suppl):368S-9S.

AUTORES / AUTHORS:  - Moore PE; Calder MM; Silverman ES; Panettieri RA Jr; Shore SA

INSTITUCIÓN / INSTITUTION:  - Departments of Pediatrics and Pharmacology (Dr. Moore and Mr. Calder), Vanderbilt University School of Medicine, Nashville, TN 37232-2586, USA.  N. Ref:: 1

 

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[13]

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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[14]

TÍTULO / TITLE:  - Effects of glatiramer acetate on relapse rate and accumulated disability in multiple sclerosis: meta-analysis of three double-blind, randomized, placebo-controlled clinical trials.

REVISTA / JOURNAL:  - Mult Scler 2003 Aug;9(4):349-55.

AUTORES / AUTHORS:  - Boneschi FM; Rovaris M; Johnson KP; Miller A; Wolinsky JS; Ladkani D; Shifroni G; Comi G; Filippi M

INSTITUCIÓN / INSTITUTION:  - Department of Neuroscience, Scientific Institute, University H San Raffaele, Milan, Italy.

RESUMEN / SUMMARY:  - Three randomized, double-blind, placebo-controlled trials have shown that glatiramer acetate (GA) is effective in reducing relapse rate in patients with relapsing-remitting (RR) multiple sclerosis (MS). Using raw data pooled from 540 patients, we performed a meta-analysis of these three trials, to investigate whether the extent of GA efficacy varies according to disease-related variables at study entry. Three regression models were developed to assess the efficacy of GA on the annualized relapse rate (primary outcome measure), on the total number of on-trial relapses and on the time to first relapse. We also explored the efficacy of GA on accumulated disability and the potential role of baseline clinical variables as predictors of relapse-rate variables and treatment efficacy. The mean adjusted annualized relapse rate on study was 1.14 in the pooled placebo-treated subjects and 0.82 in the pooled GA group (P = 0.004), indicating an average reduction in annualized relapse rate of 28%. About a one third reduction of the total number of on-trial relapses was also observed in patients receiving GA (P < 0.0001), who had a median time to the first relapse of 322 days versus a median time to the first relapse of 219 days seen in those receiving placebo (P = 0.01). A beneficial effect on accumulated disability was also found (risk ratio of 0.6; 95%; CI = 0.4-0.9; P = 0.02). The drug assignment (P = 0.004), baseline EDSS score (P = 0.02) and number of relapses during the two years prior to study entry (P = 0.002) were significant predictors of on-trial annualized relapse rate. No other demographic or clinical variable at baseline significantly influenced the treatment effect. This meta-analysis reaffirms the effectiveness of GA in reducing relapse rate and disability accumulation in RRMS, at a magnitude comparable to that of other available immunomodulating treatments. It also suggests that GA efficacy is not significantly influenced by the patients’ clinical characteristics at the time of treatment initiation.

 

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[15]

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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[16]

TÍTULO / TITLE:  - Sublingual immunotherapy for allergic rhinitis.

REVISTA / JOURNAL:  - Cochrane Database Syst Rev 2003;(2):CD002893.

AUTORES / AUTHORS:  - Wilson DR; Torres LI; Durham SR

INSTITUCIÓN / INSTITUTION:  - Upper Respiratory Medicine, Imperial College School of Medicine at the National Heart & Lung Institute, Dovehouse Street, London, UK, SW3 6LR. duncw 99@yahoo.co.uk

RESUMEN / SUMMARY:  - BACKGROUND: Allergic rhinitis is a common condition which, at its most severe, can significantly impair quality of life despite optimal treatment with antihistamines and topical nasal corticosteroids. Allergen injection immunotherapy significantly reduces symptoms and medication requirements in allergic rhinitis but its use is limited by the possibility of severe systemic reactions. There has therefore been considerable interest in alternative routes for delivery of allergen immunotherapy, particularly the sublingual route. OBJECTIVES: To evaluate the efficacy of sublingual immunotherapy (SLIT), compared with placebo, for reductions in symptoms and medication requirements. SEARCH STRATEGY: The Cochrane Controlled Trials Register, MEDLINE (1966-2002), EMBASE (1974-2002) and Scisearch were searched, up to September 2002, using the terms (Rhin* OR hay fever) AND (immunotherap* OR desensiti*ation) AND (sublingual). SELECTION CRITERIA: All studies identified by the searches were assessed by the reviewers to identify randomised controlled trials involving participants with symptoms of allergic rhinitis and proven allergen sensitivity, treated with SLIT or corresponding placebo. DATA COLLECTION AND ANALYSIS: Data from identified studies were abstracted onto a standard extraction sheet and subsequently entered into RevMan 4.1. Analysis was performed by the method of Standardised Mean Differences (SMD) using a random effects model. P values <0.05 were considered statistically significant. Subgroup analyses were performed according to the type of allergen administered, the age of participants and the duration of treatment. MAIN RESULTS: Twenty two trials involving 979 patients were included. There were 6 trials of SLIT for House Dust Mite allergy, 5 for Grass Pollen, 5 for Parietaria, 2 for Olive and one each for, Ragweed, Cat, Tree and Cupressus. Four studies enrolled exclusively children. Seventeen studies administered the allergen by sublingual drops subsequently swallowed, 3 by drops subsequently spat out and 2 by sublingual tablets. Eight studies involved treatment for less than 6 months, 10 studies for 6-12 months and 4 studies for greater than 12 months. All included studies were double-blind placebo-controlled trials of parallel group design. Concealment of treatment allocation was considered adequate in all studies and the use of identical placebo preparations was almost universal. There was significant heterogeneity, most likely due to widely differing scoring systems between studies, for most comparisons. Overall there was a significant reduction in both symptoms (SMD -0.34, 95% confidence interval -0.69 to -0.15; p=0.002) and medication requirements (SMD -0.43 [-0.63, -0.23]; p=0.00003) following immunotherapy. Subgroup analyses failed to identify a disproportionate benefit of treatment according to the allergen administered. There was no significant reduction in symptoms and medication scores in those studies involving only children but total numbers of participants were small, casting doubt on the validity of the conclusion. Increasing duration of treatment does not clearly increase efficacy. The total dose of allergen administered may be important but insufficient data were available to analyse this factor. REVIEWER’S CONCLUSIONS: SLIT is a safe treatment which significantly reduces symptoms and medication requirements in allergic rhinitis. The size of this benefit compared to that of other available therapies, particularly injection immunotherapy, is not clear, having been assessed directly in very few studies. Further research is required concentrating on optimising allergen dosage and patient selection.  N. Ref:: 41

 

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[17]

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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[18]

TÍTULO / TITLE:  - B cell-ablative therapy for the treatment of autoimmune diseases.

REVISTA / JOURNAL:  - Arthritis Rheum 2002 Aug;46(8):1984-5.

      ●● Enlace al texto completo (gratuito o de pago) 1002/art.10476

AUTORES / AUTHORS:  - Patel DD  N. Ref:: 18

 

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[19]

TÍTULO / TITLE:  - The future of antigen-specific immunotherapy of allergy.

REVISTA / JOURNAL:  - Nat Rev Immunol 2002 Jun;2(6):446-53.

      ●● Enlace al texto completo (gratuito o de pago) 1038/nri824

AUTORES / AUTHORS:  - Valenta R

INSTITUCIÓN / INSTITUTION:  - Department of Pathophysiology, University of Vienna Medical School, Vienna General Hospital-AKH, Australia. Rudolf.valenta@akh-wein.ac.at

RESUMEN / SUMMARY:  - More than 25% of the population in industrialized countries suffers from immunoglobulin-E-mediated allergies. The antigen-specific immunotherapy that is in use at present involves the administration of allergen extracts to patients with the aim to cure allergic symptoms. However, the risk of therapy-induced side effects limits its broad application. Recent work indicates that the epitope complexity of natural allergen extracts can be recreated using recombinant allergens, and hypoallergenic derivatives of these can be engineered to increase treatment safety. It is proposed that these modified molecules will improve the current practice of specific immunotherapy and form a basis for prophylactic vaccination.  N. Ref:: 120

 

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[20]

TÍTULO / TITLE:  - How I treat chronic graft-versus-host disease.

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: <> 2001 Mar 1;97(5):1196-201.

AUTORES / AUTHORS:  - Vogelsang GB

INSTITUCIÓN / INSTITUTION:  - Oncology Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231-1000, USA. vogelge@jhmi.edu

RESUMEN / SUMMARY:  - Allogeneic stem cell transplantation (SCT) is now a commonplace procedure. Clinicians who care for patients with hematologic malignancies and aplastic anemia are almost certain to follow up patients after SCT. This review is intended to help clinicians observe patients for probably the most important late complication of SCT, chronic graft-versus-host disease (GVHD). It reviews the pathophysiology, risk factors, clinical manifestations, evaluation, treatment, and supportive care of chronic GVHD.  N. Ref:: 34

 

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[21]

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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[22]

TÍTULO / TITLE:  - Clinical protocol. Purging of autologous stem cell sources with bcl-x(s) adenovirus for women undergoing high-dose chemotherapy for stage IV breast carcinoma.

REVISTA / JOURNAL:  - Hum Gene Ther 2001 Nov 1;12(16):2023-5.

AUTORES / AUTHORS:  - Ayash LJ; Clarke M; Adams P; Ferrara J; Ratanatharathorn V; Reynolds C; Roessler B; Silver S; Strawderman M; Uberti J; Wicha M

RESUMEN / SUMMARY:  - High-dose chemotherapy (HDCT) and autologous bone marrow transplantation (BMT) is frequently used to treat patients with metastatic cancer including breast cancer and neuroblastoma. However, the bone marrow of such patients is often contaminated with tumor cells. Recently, we have found that a recombinant adenovirus vector that contains a bcl-x, minigene (a dominant negative inhibitor of the bcl-2 family), called the bcl-x(s) adenovirus, is lethal to cancer cells derived from epithelial tissues, but not to normal human hematopoietic cells. To determine the mechanism, by which this virus spares normal hematopoietic cells, we isolated normal mouse hematopoietic stem cells and infected them with an adenovirus that contains a beta-galactosidase minigene. Such cells do not express beta-galactosidase, indicating that hematopoietic stem cells do not express transgene encoded by adenovirus vectors based upon the RSV-AD5 vector system. When breast cancer cells mixed with hematopoietic cells were infected with the bcl-x(s) adenovirus, cancer cells were selectively killed by the suicide adenoviruses. Hematopoietic cells exposed to the suicide vectors were able to reconstitute the bone marrow of mice exposed to lethal doses of y-irradiation. These studies suggest that adenovirus suicide vectors may provide a simple and effective method to selectively eliminate cancer cells derived from epithelial tissue that contaminate bone marrow to be used for autologous BMT. We therefore propose to initiate a phase I clinical trial to test the safety of this virus in women with breast cancer undergoing high does chemotherapy and autologous BMT.

 

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[23]

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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[24]

TÍTULO / TITLE:  - Regulatory T cells in kidney transplant recipients: active players but to what extent?

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 Jun;14(6):1706-8.

AUTORES / AUTHORS:  - Zhai Y; Kupiec-Weglinski JW  N. Ref:: 20

 

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[25]

TÍTULO / TITLE:  - IL-10 and its related cytokines for treatment of inflammatory bowel disease.

REVISTA / JOURNAL:  - World J Gastroenterol. Acceso gratuito al texto completo.

      ●● Enlace a la Editora de la Revista http://www.wjgnet.com/1007-9327/wj.htm 

      ●● Cita: World Journal of Gastroenterology: <> 2004 Mar 1;10(5):620-5.

AUTORES / AUTHORS:  - Li MC; He SH

INSTITUCIÓN / INSTITUTION:  - Allergy and Inflammation Research Institute, Shantou University Medical College, 22 Xin Ling Road, Shantou 515041, Guangdong Province, China.

RESUMEN / SUMMARY:  - Inflammatory bowel diseases (IBDs), including Crohn’s disease and ulcerative colitis are chronic inflammatory disorders of gastrointestinal tract. Although the etiology is incompletely understood, initiation and aggravation of the inflammatory process seem to be due to a massive local mucosal immune response. Interleukin-10 (IL-10) is a regulatory cytokine which inhibits both antigen presentation and subsequent pro-inflammatory cytokine release, and it is proposed as a potent anti-inflammatory biological therapy in chronic IBD. Many methods of IL-10 as a treatment for IBD have been published. The new strategies of IL-10 treatment, including recombinant IL-10, the use of genetically modified bacteria, gelatine microsphere containing IL-10, adenoviral vectors encoding IL-10 and combining regulatory T cells are discussed in this review. The advantages and disadvantages of these IL-10 therapies are summarized. Although most results of recombinant IL-10 therapies are disappointing in clinical testing because of lacking efficacy or side effects, therapeutic strategies utilizing gene therapy may enhance mucosal delivery and increase therapeutic response. Novel IL-10-related cytokines, including IL-19, IL-20, IL-22, IL-24, IL-26, IL-28 and IL-29, are involved in regulation of inflammatory and immune responses. The use of IL-10 and IL-10-related cytokines will provide new insights into cell-based and gene-based treatment against IBD in near future.  N. Ref:: 54

 

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[26]

TÍTULO / TITLE:  - Immunosuppression and xenotransplantation of cells for cardiac repair.

REVISTA / JOURNAL:  - Ann Thorac Surg 2004 Feb;77(2):737-44.

      ●● Enlace al texto completo (gratuito o de pago) 1016/j.athoracsur.2003.08.036

AUTORES / AUTHORS:  - Xiao YF; Min JY; Morgan JP

INSTITUCIÓN / INSTITUTION:  - Stem Cell Research Laboratory, The Charles A. Dana Research Institute, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA. yxiao@bidmc.harvard.edu

RESUMEN / SUMMARY:  - The death of highly vulnerable cardiomyocytes during ischemia leads to cardiac dysfunction, including heart failure. Due to limited proliferation of adult mammalian cardiomyocytes, the dead myocardium is replaced by noncontractile fibrotic tissue. Introducing exogenous cells to participate in the regeneration of infarcted myocardium has thus been proposed as a novel therapeutic approach. In view of the availability of various xenogeneic cells and fewer ethical and political concerns that surround human embryonic stem cells and fetal cardiomyocytes, cellular xenotransplantation may be a potential alternative approach for cardiac repair in humans. However, one of the most daunting challenges of xenotransplantation is immunorejection. This article summarizes the progress in cellular xenotransplantation for cardiac repair in experimental settings and the current understanding of possible immune responses following the engraftment of xenogeneic cells. The public attitude towards xenotransplantation is reportedly more favorable to receiving cells or tissues than a whole organ, but many scientific obstacles need to be overcome before the utilization of xenogeneic cells for cardiac repair in patients with heart disease becomes applicable to clinical practice.  N. Ref:: 82

 

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[27]

TÍTULO / TITLE:  - Cytokine-based immunointervention in the treatment of autoimmune diseases.

REVISTA / JOURNAL:  - Clin Exp Immunol 2003 May;132(2):185-92.

AUTORES / AUTHORS:  - Adorini L

INSTITUCIÓN / INSTITUTION:  - BioXell, Via Olgettina 58, 20132 Milan, Italy. luciano.adorini@bioxell.com  N. Ref:: 99

 

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[28]

TÍTULO / TITLE:  - Protocol core needle biopsy and histologic Chronic Allograft Damage Index (CADI) as surrogate end point for long-term graft survival in multicenter studies.

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):773-9.

AUTORES / AUTHORS:  - Yilmaz S; Tomlanovich S; Mathew T; Taskinen E; Paavonen T; Navarro M; Ramos E; Hooftman L; Hayry P

INSTITUCIÓN / INSTITUTION:  - Data Analysis Center, Division of Transplantation, Department of Surgery, University of Calgary, Alberta, Canada.

RESUMEN / SUMMARY:  - This study is an investigation of whether a protocol biopsy may be used as surrogate to late graft survival in multicenter renal transplantation trials. During two mycophenolate mofetil trials, 621 representative protocol biopsies were obtained at baseline, 1 yr, and 3 yr. The samples were coded and evaluated blindly by two pathologists, and Chronic Allograft Damage Index (CADI) score was constructed. At 1 yr, only 20% of patients had elevated (>l.5 mg/100 ml) serum creatinine, whereas 60% of the biopsies demonstrated an elevated (>2.0) CADI score. The mean CADI score at baseline, 1.3 +/- 1.1, increased to 3.3 +/- 1.8 at 1 yr and to 4.1 +/- 2.2 at 3 yr. The patients at 1 yr were divided into three groups, those with CADI <2, between 2 and 3.9, and >4.0, the first two groups having normal (1.4 +/- 0.3 and 1.5 +/- 0.6 mg/dl) and the third group pathologic (1.9 +/- 0.8 mg/dl) serum creatinine. At 3 yr, there were no lost grafts in the low CADI group, six lost grafts (4.6%) in the in the elevated CADI group, and 17 lost grafts (16.7%) in the high CADI group (P < 0.001). One-year histologic CADI score predicts graft survival even when the graft function is still normal. This observation makes it possible to use CADI as a surrogate end point in prevention trials and to identify the patients at risk for intervention trials.

 

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[29]

TÍTULO / TITLE:  - Pulmonary infiltrates in the non-HIV-infected immunocompromised patient: etiologies, diagnostic strategies, and outcomes.

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

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

      ●● Cita: Chest: <> 2004 Jan;125(1):260-71.