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Revisiones-Clínica-Pronóstico *** Reviews-Clinical-Prognosis

 

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:  - Clinical practice guidelines for managing dyslipidemias in kidney transplant patients: a report from the Managing Dyslipidemias in Chronic Kidney Disease Work Group of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative.

REVISTA / JOURNAL:  - Am J Transplant 2004;4 Suppl 7:13-53.

      ●● Enlace al texto completo (gratuito o de pago) 1111/j.1600-6135.2004.0355.x

AUTORES / AUTHORS:  - Kasiske B; Cosio FG; Beto J; Bolton K; Chavers BM; Grimm R Jr; Levin A; Masri B; Parekh R; Wanner C; Wheeler DC; Wilson PW

RESUMEN / SUMMARY:  - The incidence of cardiovascular disease (CVD) is very high in patients with chronic kidney (CKD) disease and in kidney transplant recipients. Indeed, available evidence for these patients suggests that the 10-year cumulative risk of coronary heart disease is at least 20%, or roughly equivalent to the risk seen in patients with previous CVD. Recently, the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (K/DOQI) published guidelines for the diagnosis and treatment of dyslipidemias in patients with CKD, including transplant patients. It was the conclusion of this Work Group that the National Cholesterol Education Program Guidelines are generally applicable to patients with CKD, but that there are significant differences in the approach and treatment of dyslipidemias in patients with CKD compared with the general population. In the present document we present the guidelines generated by this workgroup as they apply to kidney transplant recipients. Evidence from the general population indicates that treatment of dyslipidemias reduces CVD, and evidence in kidney transplant patients suggests that judicious treatment can be safe and effective in improving dyslipidemias. Dyslipidemias are very common in CKD and in transplant patients. However, until recently there have been no adequately powered, randomized, controlled trials examining the effects of dyslipidemia treatment on CVD in patients with CKD. Since completion of the K/DOQI guidelines on dyslipidemia in CKD, the results of the Assessment of Lescol in Renal Transplantation (ALERT) Study have been presented and published. Based on information from randomized trials conducted in the general population and the single study conducted in kidney transplant patients, these guidelines, which are a modified version of the K/DOQI dyslipidemia guidelines, were developed to aid clinicians in the management of dyslipidemias in kidney transplant patients. These guidelines are divided into four sections. The first section (Introduction) provides the rationale for the guidelines, and describes the target population, scope, intended users, and methods. The second section presents guidelines on the assessment of dyslipidemias (guidelines 1-3), while the third section offers guidelines for the treatment of dyslipidemias (guidelines 4-5). The key guideline statements are supported mainly by data from studies in the general population, but there is an urgent need for additional studies in CKD and in transplant patients. Therefore, the last section outlines recommendations for research.

 

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[2]

TÍTULO / TITLE:  - Strategies to improve long-term outcomes after renal 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): <> 2002 Feb 21;346(8):580-90.

      ●● Enlace al texto completo (gratuito o de pago) 1056/NEJMra011295

AUTORES / AUTHORS:  - Pascual M; Theruvath T; Kawai T; Tolkoff-Rubin N; Cosimi AB

INSTITUCIÓN / INSTITUTION:  - Renal Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA. mpascual@partners.org  N. Ref:: 99

 

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[3]

TÍTULO / TITLE:  - A randomized long-term trial of tacrolimus/sirolimus versus tacrolimus/mycophenolate mofetil versus cyclosporine (NEORAL)/sirolimus in renal transplantation. II. Survival, function, and protocol compliance at 1 year.

REVISTA / JOURNAL:  - Transplantation 2004 Jan 27;77(2):252-8.

      ●● Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000101495.22734.07

AUTORES / AUTHORS:  - Ciancio G; Burke GW; Gaynor JJ; Mattiazzi A; Roth D; Kupin W; Nicolas M; Ruiz P; Rosen A; Miller J

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Division of Transplantation, University of Miami School of Medicine, Miami, FL 33101, USA. gciancio@med.miami.edu

RESUMEN / SUMMARY:  - BACKGROUND: In an attempt to reduce chronic calcineurin inhibitor induced allograft nephropathy in first cadaver and human leukocyte antigen non-identical living-donor renal transplantation, sirolimus (Siro) or mycophenolate mofetil (MMF) was tested as adjunctive therapy, with planned dose reductions of tacrolimus (Tacro) over the first year postoperatively. Adjunctive Siro therapy with a similar dose reduction algorithm for Neoral (Neo) was included for comparison. METHODS: The detailed dose reduction plan (Tacro and Siro, group A; Tacro and MMF, group B; Neo and Siro, group C) is described in our companion report in this issue of Transplantation. The present report documents function, patient and graft survival, protocol compliance, and adverse events. RESULTS: As mentioned (in companion report), group demographics were similar. The present study shows no significant differences in 1-year patient and graft survival but does show a trend that points to more difficulties in group C by way of a rising slope of serum creatinine concentration (P=0.02) and decreasing creatinine clearance (P=0.04). There were more patients who discontinued the protocol plan in group C. Thus far, no posttransplant lymphomas have appeared, and infectious complications have not differed among the groups. However, a greater percentage of patients in group C were placed on antihyperlipidemia therapy, with an (unexpected) trend toward a higher incidence of posttransplant diabetes mellitus in this group. Group A required fewer, and group B the fewest, antihyperlipidemia therapeutic interventions (P<0.00001). CONCLUSIONS: This 1-year interim analysis of a long-term, prospective, randomized renal-transplant study indicates that decreasing maintenance dosage of Tacro with adjunctive Siro or MMF appears to point to improved long-term function, with reasonably few adverse events.

 

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[4]

TÍTULO / TITLE:  - Early outcome after sirolimus-eluting stent implantation in patients with acute coronary syndromes: insights from the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) registry.

REVISTA / JOURNAL:  - J Am Coll Cardiol 2003 Jun 4;41(11):2093-9.

AUTORES / AUTHORS:  - Lemos PA; Lee CH; Degertekin M; Saia F; Tanabe K; Arampatzis CA; Hoye A; van Duuren M; Sianos G; Smits PC; de Feyter P; van der Giessen WJ; van Domburg RT; Serruys PW

INSTITUCIÓN / INSTITUTION:  - Department of Cardiology, Thoraxcenter, Erasmus Medical Center, Dr Molewaterplein 40, NL-3015 GD Rotterdam, the Netherlands.

RESUMEN / SUMMARY:  - OBJECTIVES: This study evaluated the early outcomes of patients with acute coronary syndromes (ACS) treated with sirolimus-eluting stents (SES). BACKGROUND: The safety of SES implantation in patients with a high risk for early thrombotic complications is currently unknown. METHODS: Sirolimus-eluting stents have been utilized as the device of choice for all percutaneous procedures in our institution, as part of the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) registry. After four months of enrollment, 198 patients with ACS had been treated exclusively with SES (64% of those treated in the period) and were compared with a control group composed of 301 consecutive patients treated with bare stents in the same time period immediately before this study. The incidence of major adverse cardiac events (MACE) during the first month was evaluated (death, nonfatal myocardial infarction [MI], or re-intervention). RESULTS: Compared with control patients, patients treated with SES had more primary angioplasty (95% vs. 77%; p < 0.01), more bifurcation stenting (13% vs. 5%; p < 0.01), less previous MI (28% vs. 45%; p < 0.01), and less glycoprotein IIb/IIIa inhibitor utilization (27% vs. 42%; p < 0.01). The 30-day MACE rate was similar between both groups (SES 6.1% vs. control patients 6.6%; p = 0.8), with most complications occurring during the first week. Stent thrombosis occurred in 0.5% of SES patients and in 1.7% of control patients (p = 0.4). In multivariate analysis, SES utilization did not influence the incidence of MACE (odds ratio 1.0 [95% confidence interval: 0.4 to 2.2]; p = 0.97). CONCLUSIONS: Sirolimus-eluting stent implantation for patients with ACS is safe, with early outcomes comparable with bare metal stents.  N. Ref:: 25

 

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[5]

TÍTULO / TITLE:  - Treatment and outcome of invasive bladder cancer in patients after renal transplantation.

REVISTA / JOURNAL:  - J Urol 2004 Mar;171(3):1085-8.

      ●● Enlace al texto completo (gratuito o de pago) 1097/01.ju.0000110612.42382.0a

AUTORES / AUTHORS:  - Master VA; Meng MV; Grossfeld GD; Koppie TM; Hirose R; Carroll PR

INSTITUCIÓN / INSTITUTION:  - Departments of Urology and Surgery, University of California, San Francisco, California 94143, USA. vmaster@urol.ucsf.edu

RESUMEN / SUMMARY:  - PURPOSE: Optimal management and clinical outcome of bladder cancer in renal transplant recipients are not well-defined. We analyzed single institution treatment strategies and outcomes of these patients. MATERIALS AND METHODS: We retrospectively reviewed the University of California, San Francisco transplant database which contains information on 6,288 renal transplants performed between 1964 and 2002. The United Network for Organ Sharing database and Israel Penn International Transplant Tumor Registry were also queried to characterize the global nature of bladder cancer in renal transplant recipients. RESULTS: The United Network for Organ Sharing database (1986 to 2001) contained information on 31 patients who were found to have bladder cancer (0.024% prevalence) and the Israel Penn International Transplant Tumor Registry (1967 to 2001) contained information on 135 patients representing 0.84% of all reported malignancies. We identified 7 renal transplant recipients with bladder cancer at our institution. Invasive transitional cell carcinoma developed in 5 patients at a median of 2.8 years after transplant. Three patients underwent uncomplicated radical cystectomy and preservation of the renal allograft. Overall survival at 48 months was 60%. CONCLUSIONS: Bladder cancer after renal transplantation is not common. For patients who present with invasive disease, traditional extirpative surgery should be considered. Moreover, the allograft is rarely the source of transitional cell carcinoma and can be preserved. In our experience the cancer and urinary outcomes compare favorably with nontransplant patient outcomes after treatment.  N. Ref:: 21

 

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[6]

TÍTULO / TITLE:  - Patient and graft survival following liver transplantation for hepatitis C: much ado about something.

REVISTA / JOURNAL:  - Gastroenterology 2002 Apr;122(4):1162-5.

AUTORES / AUTHORS:  - Charlton M  N. Ref:: 20

 

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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:  - Routes to allograft survival.

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

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

      ●● Cita: J Clinical Investigation: <> 2001 Apr;107(7):797-8.

AUTORES / AUTHORS:  - Bromberg JS; Murphy B

INSTITUCIÓN / INSTITUTION:  - Recanati/Miller Transplant Institute, Mount Sinai School of Medicine, New York, New York 10029, USA. jon.bromberg@mountsinai.org  N. Ref:: 21

 

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[9]

TÍTULO / TITLE:  - Cell survival and clinical outcome following intrastriatal transplantation in Parkinson disease.

REVISTA / JOURNAL:  - J Neuropathol Exp Neurol 2001 Aug;60(8):741-52.

AUTORES / AUTHORS:  - Hagell P; Brundin P

INSTITUCIÓN / INSTITUTION:  - Department of Clinical Neuroscience, University Hospital, Lund University, Sweden.

RESUMEN / SUMMARY:  - Intrastriatal transplantation of embryonic dopaminergic neurons is currently explored as a restorative cell therapy for Parkinson disease (PD). Clinical results have varied, probably due to differences in transplantation methodology and patient selection. In this review, we assess clinical trials and autopsy findings in grafted PD patients and suggest that a minimum number of surviving dopaminergic neurons is required for a favorable outcome. Restoration of [18F]-fluorodopa uptake in the putamen to about 50% of the normal mean seems necessary for moderate to marked clinical benefit to occur. Some studies indicate that this may require mesencephalic tissue from 3-5 human embryos implanted into each hemisphere. The volume, density and pattern of fiber outgrowth and reinnervation, as well as functional integration and dopamine release. are postulated as additional important factors for an optimal clinical outcome. For neural transplantation to become a feasible therapeutic alternative in PD, graft survival must be increased and the need for multiple donors of human embryonic tissue substantially decreased or alternate sources of donor tissue developed. Donor cells derived from alternative sources should demonstrate features comparable to those associated with successful implantation of human embryonic tissue before clinical trials are considered.  N. Ref:: 62

 

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[10]

TÍTULO / TITLE:  - Valacyclovir provides optimum acyclovir exposure for prevention of cytomegalovirus and related outcomes after organ transplantation.

REVISTA / JOURNAL:  - J Infect Dis. Acceso gratuito al texto completo a partir de los 2 años de la publicación;  - http://www.journals.uchicago.edu/ 

      ●● Cita: J. of Infectious Diseases: <> 2002 Oct 15;186 Suppl 1:S110-5.

AUTORES / AUTHORS:  - Fiddian P; Sabin CA; Griffiths PD

INSTITUCIÓN / INSTITUTION:  - Royal Free and University College Medical School (Royal Free Campus), London NW3 2PF, United Kingdom. paul.fiddian@which.net

RESUMEN / SUMMARY:  - A meta-analysis of 12 randomized trials (1574 patients) examined herpesvirus and related outcomes following organ transplantation over a range of acyclovir exposures (including valacyclovir). Overall, cytomegalovirus (CMV) infection (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.34-0.57; P<.001), CMV disease (OR, 0.41; 95% CI, 0.31-0.54; P<.001), death (OR, 0.60; 95% CI, 0.40-0.90; P=.01), opportunistic infection (OR, 0.70; 95% CI, 0.53-0.91; P=.009), acute graft rejection (OR, 0.67; 95% CI, 0.52-0.86; P<.001), herpes simplex virus disease (OR, 0.17; 95% CI, 0.12-0.24; P<.001), and varicella-zoster virus disease (OR, 0.06; 95% CI, 0.01-0.25; P<.001) were significantly reduced. Increased acyclovir exposure influenced more end points: Maximum efficacy resulted from valacyclovir (8 g/day). Increasing acyclovir exposure to that achieved with valacyclovir extends benefits of prophylaxis to include impact on graft rejection and opportunistic infections.

 

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[11]

TÍTULO / TITLE:  - Survival after HLA-identical allogeneic peripheral blood stem cell and bone marrow transplantation for hematologic malignancies: meta-analysis of randomized controlled trials.

REVISTA / JOURNAL:  - Bone Marrow Transplant 2003 Aug;32(3):293-8.

      ●● Enlace al texto completo (gratuito o de pago) 1038/sj.bmt.1704112

AUTORES / AUTHORS:  - Horan JT; Liesveld JL; Fernandez ID; Lyman GH; Phillips GL; Lerner NB; Fisher SG

INSTITUCIÓN / INSTITUTION:  - Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.

RESUMEN / SUMMARY:  - The impact of peripheral blood stem cell transplantation (PBSCT) on survival relative to bone marrow transplantation (BMT) remains poorly defined. Several randomized controlled trials (RCTs) comparing HLA-matched related PBSC- and BMT for patients with hematologic malignancies have been published, yielding differing results. We conducted a meta-analysis of published RCTs to more precisely estimate the effect of PBSCT on survival. Seven trials that assessed survival were identified and included in our analysis. Using a fixed effects model, and combining the results of all seven trials, the summary odds ratio for mortality after PBSCT was 0.81 (95% CI, 0.62-1.05) when compared to BMT. Subgroup analysis revealed no association between the median PBSCT 34+ cell dose and relative risk for morality after PBSCT. However, there was an association between the proportion of patients enrolled with advanced-stage disease and the summary odds ratio for mortality. The pooled estimate was 0.64 for studies where patients with intermediate/advanced disease comprised at least 25% of enrollment, and was 1.07 for the studies enrolling a smaller proportion. This finding substantiates results from previously published studies that have demonstrated a survival advantage with PBSCT limited to patients with advanced disease.

 

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[12]

TÍTULO / TITLE:  - One-year survival in patients with acute myocardial infarction and a saphenous vein graft culprit treated with primary angioplasty.

REVISTA / JOURNAL:  - Am J Cardiol 2003 May 15;91(10):1250-4.

AUTORES / AUTHORS:  - Nguyen TT; O’Neill WW; Grines CL; Stone GW; Brodie BR; Cox DA; Grines LL; Boura JA; Dixon SR

INSTITUCIÓN / INSTITUTION:  - William Beaumont Hospital, Royal Oak, Michigan 48073, USA.

 

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[13]

TÍTULO / TITLE:  - Prediction of an HLA-DR-binding peptide derived from Wilms’ tumour 1 protein and demonstration of in vitro immunogenicity of WT1(124-138)-pulsed dendritic cells generated according to an optimised protocol.

REVISTA / JOURNAL:  - Cancer Immunol Immunother 2002 Jul;51(5):271-81. Epub 2002 Apr 26.

      ●● Enlace al texto completo (gratuito o de pago) 1007/s00262-002-0278-2

AUTORES / AUTHORS:  - Knights AJ; Zaniou A; Rees RC; Pawelec G; Muller L

INSTITUCIÓN / INSTITUTION:  - University of Tubingen, Section for Transplantation Immunology and Immunohaematology, Second Department of Internal Medicine, Zentrum fur Medizinische Forschung ZMF, Waldhornlestrasse 22, 72072 Tubingen, Germany.

RESUMEN / SUMMARY:  - The Wilms’ tumour 1 (WT1) protein is over-expressed in several types of cancer including leukaemias and might therefore constitute a novel target for immunotherapy. Recently, human leucocyte antigen (HLA) class I-binding WT1 peptides have been identified and shown to stimulate CD8(+) T cells in vitro. For maximal CD8 cell efficacy, CD4(+) helper T cells responding to major histocompatibility complex (MHC) class II-binding epitopes are required. Here, we report that scanning the WT1 protein sequence using an evidence-based predictive computer algorithm (SYFPEITHI) yielded a peptide WT1(124-138) predicted to bind the HLA-DRB1*0401 molecule with high affinity. Moreover, synthetic WT1(124-138)-peptide-pulsed dendritic cells (DC), generated according to a protocol optimised in the present study, sensitised T cells in vitro to proliferate and secrete interferon-gamma (IFN-gamma) when rechallenged with specific peptide-pulsed DC, but not with peripheral blood mononuclear cells (PBMC). These results suggest that the WT1 protein may yield epitopes immunogenic to CD4 as well as CD8 T cells, and therefore constitute a novel potential target for specific immunotherapy.

 

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[14]

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

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

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

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

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

 

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[15]

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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[16]

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.

AUTORES / AUTHORS:  - Shorr AF; Susla GM; O’Grady NP

INSTITUCIÓN / INSTITUTION:  - Pulmonary and Critical Care Medicine Service, Walter Reed Army Medical Center, Washington, DC 20307, USA. afshorr@dnamail.com

RESUMEN / SUMMARY:  - Pulmonary complications remain a major cause of both morbidity and mortality in immunocompromised patients. When such individuals present with radiographic infiltrates, the clinician faces a diagnostic challenge. The differential diagnosis in this setting is broad and includes both infectious and noninfectious processes. Rarely are the radiographic findings classic for one disease, and most potential etiologies have overlapping clinical and radiographic appearances. In recent years, several themes have emerged in the literature on this topic. First, an aggressive approach to identifying a specific etiology is necessary; as a corollary, diagnostic delay increases the risk for mortality. Second, the evaluation of these infiltrates nearly always entails bronchoscopy. Bronchoscopy allows identification of some etiologies with certainty, and often allows for the exclusion of infectious agents even if the procedure is otherwise unrevealing. Third, early use of CT scanning regularly demonstrates lesions missed by plain radiography. Despite these advances, initial therapeutic interventions include the use of broad-spectrum antibiotics and other anti-infectives in order to ensure that the patients is receiving appropriate therapy. With the results of invasive testing, these treatments are then narrowed. Frustratingly, outcomes for immunocompromised patients with infiltrates remain poor.  N. Ref:: 58

 

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[17]

TÍTULO / TITLE:  - European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.13 Analysis of patient and graft survival.

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 4:60-7.

RESUMEN / SUMMARY:  - GUIDELINES: A. It is important for a transplant unit to follow-up on the results of their transplant activities. In order to achieve correct reports on graft and patient outcome in all patients, it is necessary to have sufficient resources, such as a computerized database, and continuous updates of patient information. All data collected should be subjected to validation procedures to ensure completeness and accuracy. B. Improved outcomes following implementation of new protocols, based on evaluation of clinical multi-centre trials, should be verified at local transplant centres since centres often include a range of patients different from those selected for the trial. C. The most widely accepted descriptor of outcome is the Kaplan-Meier probability estimate of patient and graft survival. Survival estimates should be calculated at intervals of time after transplantation and should always be expressed with their 95% confidence intervals. D. Kaplan-Meier survival estimates may be calculated in three ways. (i) ‘Patient survival’ should be calculated from the date of transplantation to the date of death or the date of the last follow-up. (ii) ‘Graft survival’ (non-censored for death) should be calculated from the date of transplantation to the date of irreversible graft failure signified by return to long-term dialysis (or retransplantation) or the date of the last follow-up during the period when the transplant was still functioning or to the date of death. Here, death with graft function is treated as graft failure. (iii) ‘Graft survival censored for death with a functioning graft’ (death-censored graft survival) should be calculated from the date of transplantation to the date of irreversible graft failure signified by return to long-term dialysis (or retransplantation) or the date of last follow-up during the period when the transplant was still functioning. In the event of death with a functioning graft, the follow-up period is censored at the date of death. E. The outcome of transplants carried out at a centre should be compared with those achieved across a range of data from centres collated by national and international multi-centre registries. Interpretation of a centre’s performance should take into account the number of transplants performed and the prevalence of major risk factors. F. Major risk factors that influence transplant outcome are identifiable by applying multivariate analytical methods to large multi-centre follow-up databases. Although these major risk factors may not be identifiable in individual centre data, they should nonetheless be taken into account in patient management. G. When designing a clinical trial or evaluating data from a recent trial, the expected improvement in graft survival resulting from a reduction in acute rejection may be estimated from a knowledge of the rejection and graft survival rates that existed prior to the introduction of the new therapeutic regimen. H. When designing or evaluating a clinical trial, it is important to analyse the power of the study to verify statistically the difference (in graft survival) that might be expected and its statistical significance. A study resulting in absence of statistically significant differences between two treatment groups with insufficient statistical power to verify a difference at the expected level should not be taken as evidence of absence of a true difference.

 

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[18]

TÍTULO / TITLE:  - Renal function as a predictor of long-term graft survival in renal transplant patients.

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: <> 2003 May;18 Suppl 1:i3-6.

AUTORES / AUTHORS:  - First MR

INSTITUCIÓN / INSTITUTION:  - Research and Development, Fujisawa Healthcare, Inc., Deerfield, IL 60015, USA. roy_first@fujisawa.com

RESUMEN / SUMMARY:  - Acute rejection is a major risk factor for kidney graft failure. However, as acute rejection has been progressively reduced by recent immunosuppressive regimens, other risk factors are becoming increasingly important. Evidence is accumulating that early renal function predicts long-term outcome. A recent registry survey of more than 100 000 kidney transplants found that 6- and 12-month serum creatinine levels, as well as the change between 6 and 12 months, are strongly associated with long-term graft survival. A survey of paediatric renal transplant recipients showed that poor creatinine clearance (<50 ml/min) as early as 30 days post-transplant predicted an annual rate of graft loss of 13% compared with <3% in patients with 30-day clearance >50 ml/min. This association between early renal function and long-term outcome was confirmed in multicentre studies. Renal transplant recipients (n=572) with 6-month serum creatinine levels >1.5 mg/dl suffered 3-year graft loss of 19.3% compared with only 8.5% in patients with levels <1.6 mg/dl (P<0.001). Significantly fewer patients receiving tacrolimus had 12-month serum creatinine levels >1.5 mg/dl compared with cyclosporin (42 versus 54%, P<0.05). Interestingly, a single-centre study (n=436) found that while glomerular filtration rate (GFR) at 6 months post-transplant had remained stable over the last decade, the rate of loss of renal function had decreased. A lower rate of GFR loss was associated with absence of rejection, use of mycophenolate mofetil rather than azathioprine and use of tacrolimus rather than cyclosporin (P<0.01). In conclusion, early measures of renal function allow identification of those patients at highest risk of graft failure and provide an invaluable tool for improving outcomes by tailored immunosuppression. The choice of such immunosuppression should be guided not only by its ability to prevent rejection, but also by its impact on renal function.  N. Ref:: 11

 

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[19]

TÍTULO / TITLE:  - Hematopoietic cell transplantation for inherited metabolic diseases: an overview of outcomes and practice guidelines.

REVISTA / JOURNAL:  - Bone Marrow Transplant 2003 Feb;31(4):229-39.

      ●● Enlace al texto completo (gratuito o de pago) 1038/sj.bmt.1703839

AUTORES / AUTHORS:  - Peters C; Steward CG

INSTITUCIÓN / INSTITUTION:  - Department of Pediatrics, University of Minnesota School of Medicine, Minneapolis, 55455, USA.

RESUMEN / SUMMARY:  - For the past two decades, hematopoietic cell transplantation (HCT) has been used as effective therapy for selected inherited metabolic diseases (IMD) including Hurler (MPS IH) and Maroteaux-Lamy (MPS VI) syndromes, childhood-onset cerebral X-linked adrenoleukodystrophy (X-ALD), globoid-cell leukodystrophy (GLD), metachromatic leukodystrophy (MLD), alpha-mannosidosis, osteopetrosis, and others. Careful pre-HCT evaluation is critical and coordinated, multidisciplinary follow-up is essential in this field of transplantation. The primary goals of HCT for these disorders have been to promote long-term survival with donor-derived engraftment and to optimize the quality of life. Guidelines for HCT and monitoring are provided; a brief overview of long-term results is also presented.  N. Ref:: 131

 

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[20]

TÍTULO / TITLE:  - Clinical outcomes and insulin secretion after islet transplantation with the Edmonton protocol.

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

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

      ●● Cita: Diabetes: <> 2001 Apr;50(4):710-9.

AUTORES / AUTHORS:  - Ryan EA; Lakey JR; Rajotte RV; Korbutt GS; Kin T; Imes S; Rabinovitch A; Elliott JF; Bigam D; Kneteman NM; Warnock GL; Larsen I; Shapiro AM

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, Surgical Medical Research Institute, University of Alberta, Edmonton, Canada. edmond.ryan@ualberta.ca

RESUMEN / SUMMARY:  - Islet transplantation offers the prospect of good glycemic control without major surgical risks. After our initial report of successful islet transplantation, we now provide further data on 12 type 1 diabetic patients with brittle diabetes or problems with hypoglycemia previous to 1 November 2000. Details of metabolic control, acute complications associated with islet transplantation, and long-term complications related to immunosuppression therapy and diabetes were noted. Insulin secretion, both acute and over 30 min, was determined after intravenous glucose tolerance tests (IVGTTs). The median follow-up was 10.2 months (CI 6.5-17.4), and the longest was 20 months. Glucose control was stable, with pretransplant fasting and meal tolerance-stimulated glucose levels of 12.5+/-1.9 and 20.0+/-2.7 mmol/l, respectively, but decreased significantly, with posttransplant levels of 6.3+/-0.3 and 7.5+/-0.6 mmol/l, respectively (P < 0.006). All patients have sustained insulin production, as evidenced by the most current baseline C-peptide levels 0.66+/-0.06 nmol/l, increasing to 1.29+/-0.25 nmol/l 90 min after the meal-tolerance test. The mean HbA1c level decreased from 8.3+/-0.5% to the current level of 5.8+/-0.1% (P < 0.001). Presently, four patients have normal glucose tolerance, five have impaired glucose tolerance, and three have post-islet transplant diabetes (two of whom need oral hypoglycemic agents and low-dose insulin (<10 U/day). Three patients had a temporary increase in their liver-function tests. One patient had a thrombosis of a peripheral branch of the right portal vein, and two of the early patients had bleeding from the hepatic needle puncture site; but these technical problems were resolved. Two patients had transient vitreous hemorrhages. The two patients with elevated creatinine levels pretransplant had a significant increase in serum creatinine in the long term, although the mean serum creatinine of the group was unchanged. The cholesterol increased in five patients, and lipid-lowering therapy was required for three patients. No patient has developed cytomegalovirus infection or disease, posttransplant lymphoproliferative disorder, malignancies, or serious infection to date. None of the patients have been sensitized to donor antigen. In 11 of the 12 patients, insulin independence was achieved after 9,000 islet equivalents (IEs) per kilogram were transplanted. The acute insulin response and the insulin area under the curve (AUC) after IVGTT were consistently maintained over time. The insulin AUC from the IVGTT correlated to the number of islets transplanted, but more closely correlated when the cold ischemia time was taken into consideration (r = 0.83, P < 0.001). Islet transplantation has successfully corrected labile type 1 diabetes and problems with hypoglycemia, and our results show persistent insulin secretion. After a minimum of 9,000 IEs per kilogram are provided, insulin independence is usually attained. An elevation of creatinine appears to be a contraindication to this immunosuppressive regimen. For the subjects who had labile type 1 diabetes that was difficult to control, the risk-to-benefit ratio is in favor of islet transplantation.

 

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[21]

TÍTULO / TITLE:  - European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.1. Organization of follow-up of transplant patients after the first year.

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 4:3-4.

RESUMEN / SUMMARY:  - GUIDELINES: A. All renal transplant recipients should undergo regular laboratory check-ups (at least every 2 or 3 months) and regular medical visits as out-patients (at least every 4-6 months) after the first year post-transplant. B. All renal transplant recipients should be seen at least once a year in the transplant centre where the transplantation has been performed or referred to a closer transplant centre for a complete annual evaluation.

 

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[22]

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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[23]

TÍTULO / TITLE:  - Prospects for treatment of paraquat-induced lung fibrosis with immunosuppressive drugs and the need for better prediction of outcome: a systematic review.

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

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

      ●● Cita: QJM: <> 2003 Nov;96(11):809-24.

AUTORES / AUTHORS:  - Eddleston M; Wilks MF; Buckley NA

INSTITUCIÓN / INSTITUTION:  - Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, UK. eddlestonm@eureka.lk

RESUMEN / SUMMARY:  - BACKGROUND: Acute paraquat self-poisoning is a significant problem in parts of Asia, the Pacific and the Caribbean. Ingestion of large amounts of paraquat results in rapid death, but smaller doses often cause a delayed lung fibrosis that is usually fatal. Anti-neutrophil (‘immunosuppressive’) treatment has been recommended to prevent lung fibrosis, but there is no consensus on efficacy. Aim: To review the evidence for the use of immunosuppression in paraquat poisoning, and to identify validated prognostic systems that would allow the use of data from historical control studies and the future identification of patients who might benefit from immunosuppression. DESIGN:Systematic review. METHODS: We searched PubMed, Embase and Cochrane databases for ‘paraquat’ together with ‘poisoning’ or ‘overdose’. We cross-checked references and contacted experts, and searched on [www.google.com] and [www.yahoo.com] using ‘paraquat’, ‘cyclophosphamide’, ‘methylprednisolone’ and ‘prognosis’. RESULTS: We found ten clinical studies of immunosuppression in paraquat poisoning. One was a randomized controlled trial (RCT). Seven used historical controls only; the other two were small (n = 1 and n = 4). Mortality in controls and patients varied markedly between studies. Three of the seven non-RCT controlled studies measured plasma paraquat; analysis using Proudfoot’s or Hart’s nomograms did not suggest that immunosuppression increased survival in these studies. Of 16 prognostic systems for paraquat poisoning, none has been independently validated in a large cohort. DISCUSSION: The authors of the RCT have performed valuable and difficult research, but their results are hypothesis-forming rather than conclusive; elsewhere, the use of historical controls is problematic. In the absence of a validated prognostic marker, a large RCT of immunosuppression using death as the primary outcome is required. This RCT should also prospectively test and validate the available prognostic methods, so that future patients can be selected for this and other therapies on admission.  N. Ref:: 57

 

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[24]

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

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

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

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

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

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

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

 

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[25]

TÍTULO / TITLE:  - Longitudinal profile of bronchoalveolar lavage cell characteristics in patients with a good outcome after lung transplantation.

REVISTA / JOURNAL:  - Am J Respir Crit Care Med. Acceso gratuito al texto completo a partir de 1 año de la fecha de publicación.

      ●● Enlace a la Editora de la Revista http://ajrccm.atsjournals.org/ 

      ●● Cita: Am J. of Respir & Crit Care Med: <> 2002 Feb 15;165(4):501-7.

AUTORES / AUTHORS:  - Slebos DJ; Scholma J; Boezen HM; Koeter GH; van der Bij W; Postma DS; Kauffman HF

INSTITUCIÓN / INSTITUTION:  - Department of Pulmonary Diseases, University Hospital, University of Groningen, The Netherlands. D.Slebos@int.azg.nl

RESUMEN / SUMMARY:  - Bronchoalveolar lavage fluid (BALF) analysis is used in patients after lung transplantation (LTX) to obtain more insight into pathological conditions such as acute and chronic allograft rejection. Information on the normal course of BALF cell characteristics in patients with “good outcome” after LTX is limited. Therefore we analyzed 169 BALF samples from 63 well-defined “good outcome” patients after LTX (no acute or chronic transplant dysfunction, bacterial, fungal, or viral infections at the time of BAL). Total cell count decreased from