#07#
Revisiones-Clínica-Complicaciones
*** Reviews-Clinical-Complications
AGENTES
INMUNOSUPRESORES *** IMMUNOSUPPRESSIVE COMPOUNDS
(Conceptos
/ Keywords: Immunosuppressive comp; Muromonab-cd3; Sirolimus; Tacrolimus;
Cyclosporine; Mycophenolic acid; Antilymphocyte serum; Immunosuppressive comp.
used in oncology, etc).
Enero /
January 2001 --- Marzo / March 2004
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[1]
TÍTULO / TITLE: - Interleukin-2 receptor
monoclonal antibodies in renal transplantation: meta-analysis of randomised
trials.
REVISTA
/ JOURNAL: - British Medical J (BMJ). Acceso gratuito
al texto completo.
●●
Enlace a la Editora de la Revista http://bmj.com/search.dtl
●●
Cita: British Medical J. (BMJ): <> 2003 Apr 12;326(7393):789.
●●
Enlace al texto completo (gratuito o de pago) 1136/bmj.326.7393.789
AUTORES
/ AUTHORS: - Adu D; Cockwell P; Ives NJ; Shaw J;
Wheatley K
INSTITUCIÓN
/ INSTITUTION: - Department of Nephrology, Queen Elizabeth
Hospital, Birmingham, B15 2TH. dwomoa.adu@uhb.nhs.uk
RESUMEN
/ SUMMARY: - OBJECTIVE: To study the effect of
interleukin-2 receptor monoclonal antibodies on acute rejection episodes, graft
loss, deaths, and rate of infection and malignancy in patients with renal
transplants. DESIGN: Meta-analysis of published data. DATA SOURCES: Medline,
Embase, and Cochrane library for years 1996-2003 plus search of medical
editors’ trial amnesty and contact with manufacturers of the antibodies.
SELECTION OF STUDIES: Randomised controlled trials comparing interleukin-2
receptor antibodies with placebo or no additional treatment in patients with
renal transplants receiving ciclosporin based immunosuppression. RESULTS: Eight
randomised controlled trials involving 1871 patients met the selection criteria
(although only 1858 patients were analysed). Interleukin-2 receptor antibodies
significantly reduced the risk of acute rejection (odds ratio 0.51, 95%
confidence interval 0.42 to 0.63). There were no significant differences in the
rate of graft loss (0.78, 0.58 to 1.04), mortality (0.75, 0.46 to 1.23),
overall incidence of infections (0.97, 0.77 to 1.24), incidence of
cytomegalovirus infections (0.81, 0.62 to 1.04), or risk of malignancies at one
year (0.82, 0.39 to 1.70). The different antibodies had a similar sized effect
on acute rejection (test for heterogeneity P=0.7): anti-Tac (0.37, 0.16 to
0.89), BT563 (0.37, 0.1 to 1.38), basiliximab (0.56, 0.44 to 0.72), and
daclizumab (0.46, 0.32 to 0.67). The reduction in acute rejections was similar
for all ciclosporin based immunosuppression regimens (test for heterogeneity
P=1.0). CONCLUSIONS: Adding interleukin-2 receptor antibodies to ciclosporin
based immunosuppression reduces episodes of acute rejection at six months by
49%. There is no evidence of an increased risk of infective complications.
Longer follow up studies are needed to confirm whether interleukin-2 receptor
antibodies improve long term graft and patient survival.
----------------------------------------------------
[2]
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.
----------------------------------------------------
[3]
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.
----------------------------------------------------
[4]
TÍTULO / TITLE: - Risk for myopathy with
statin therapy in high-risk patients.
REVISTA
/ JOURNAL: - Arch Intern Med 2003 Mar 10;163(5):553-64.
AUTORES
/ AUTHORS: - Ballantyne CM; Corsini A; Davidson MH;
Holdaas H; Jacobson TA; Leitersdorf E; Marz W; Reckless JP; Stein EA
INSTITUCIÓN
/ INSTITUTION: - Center for Cardiovascular Disease
Prevention, Baylor College of Medicine, 6565 Fannin, Mail Station A601, Suite
A656, Houston, TX 77030, USA. cmb@bcm.tmc.edu
RESUMEN
/ SUMMARY: - Emerging data suggest that the
3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins)
offer important benefits for the large population of individuals at high risk
for coronary heart disease. This population encompasses a sizable portion of
individuals who are also at high risk for drug-drug interactions due to their
need for multiple medications. In general, statins are associated with a very
small risk for myopathy (which may progress to fatal or nonfatal
rhabdomyolysis); however, the potential for drug-drug interactions is known to
increase this risk in specific high-risk groups. The incidence of myopathy
associated with statin therapy is dose related and is increased when statins
are used in combination with agents that share common metabolic pathways. Of
particular concern is the potential for interactions with other lipid-lowering
agents such as fibrates and niacin (nicotinic acid), which may be used in
patients with mixed lipidemia, and with immunosuppressive agents, such as
cyclosporine, which are commonly used in patients after transplantation.
Clinicians should be alert to the potential for drug-drug interactions to
minimize the risk of myopathy during long-term statin therapy in patients at
high risk for coronary heart disease. N.
Ref:: 128
----------------------------------------------------
[5]
TÍTULO / TITLE: - Renal transplantation:
can we reduce calcineurin inhibitor/stop steroids? Evidence based on protocol
biopsy findings.
REVISTA
/ JOURNAL: - J Am Soc Nephrol. Acceso gratuito al texto
completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.jasn.org/
●●
Cita: Journal of the American Society of Nephrology: <> 2003
Mar;14(3):755-66.
AUTORES
/ AUTHORS: - Gotti E; Perico N; Perna A; Gaspari F;
Cattaneo D; Caruso R; Ferrari S; Stucchi N; Marchetti G; Abbate M; Remuzzi G
INSTITUCIÓN
/ INSTITUTION: - Department of Medicine and
Transplantation, Ospedali Riuniti di Bergamo, Mario Negri Institute for
Pharmacological Research, Italy.
RESUMEN
/ SUMMARY: - How to combine antirejection drugs and
which is the optimal dose of steroids and calcineurin inhibitors beyond the
first year after kidney transplantation to maintain adequate immunosuppression
without major side effects are far from clear. Kidney transplant patients on
steroid, cyclosporine (CsA), and azathioprine were randomized to per-protocol
biopsy (n = 30) or no-biopsy (n = 29) 1 to 2 yr posttransplant. Steroid or CsA
were discontinued or reduced on the basis of biopsy to establish effects on
drug-related complications, acute rejection, and graft function over 3 yr of
follow-up. Serum creatinine, GFR (plasma clearance of iohexol), RPF (renal
clearance of p-aminohippurate), CsA pharmacokinetics, and adverse events were
monitored yearly. At the end, patients underwent a second biopsy. Per-protocol
biopsy histology revealed no lesions (n = 5, steroid withdrawal), CsA
nephropathy (n = 13, CsA discontinuation/reduction), or chronic rejection (n =
12, standard therapy). Reducing the drug regimen led to overall fewer side
effects related to immunosuppression as compared with standard therapy or
no-biopsy. Steroids were safely stopped with no acute rejection or graft loss.
Complete CsA discontinuation was associated with acute rejection in the first
four patients. Lowering CsA to low target CsA trough (30 to 70 ng/ml) never led
to acute rejection or major renal function deterioration. Biopsy patients on
conventional regimen had no acute rejection, one graft loss, no significant
change in GFR, and significant RPF decline. No-biopsy controls: no acute
rejection, one graft loss, significant decline of GFR and RPF. By serial biopsy
analysis, severe lesions did not develop in patients with steroid
discontinuation in contrast to patients on standard therapy over follow-up. CsA
reduction did not adversely affect histology. Per-protocol biopsy more than 1
yr after kidney transplantation is a safe procedure to guide change of drug
regimen and to lower the risk of major side effects.
----------------------------------------------------
[6]
TÍTULO / TITLE: - Longstanding
obliterative panarteritis in Kawasaki disease: lack of cyclosporin A effect.
REVISTA
/ JOURNAL: - Pediatrics 2003 Oct;112(4):986-92.
AUTORES
/ AUTHORS: - Kuijpers TW; Biezeveld M; Achterhuis A;
Kuipers I; Lam J; Hack CE; Becker AE; van der Wal AC
INSTITUCIÓN
/ INSTITUTION: - Emma Children’s Hospital, Academic Medical
Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. t.w.kuijpers@amc.uva.nl
RESUMEN
/ SUMMARY: - Kawasaki disease is a childhood vasculitis
of medium-sized vessels, affecting the coronary arteries in particular. We have
treated a therapy-resistant child who met all diagnostic criteria for Kawasaki
disease. After the boy was given intravenous immunoglobulins and salicylates,
as well as several courses of pulsed methylprednisolone, disease recurred and
coronary artery lesions became progressively detectable. Cyclosporin A was
started and seemed clinically effective. In contrast to the positive effect on
inflammatory parameters, ie, C-reactive protein and white blood cell counts, a
novel plasma marker for cytotoxicity (granzyme B) remained elevated. Coronary
disease progressed to fatal obstruction and myocardial infarction.
Echocardiography, electrocardiograms, and myocardial creatine phosphokinase did
not predict impending death. At autopsy an obliterative panarteritis was
observed resulting from massive fibrointimal proliferation, affecting the aorta
and several large and medium-sized arteries. Immunophenotypic analysis of the
inflammatory infiltrates in arteries revealed mainly granzyme-positive
cytotoxic T cells and macrophages in the intima and media, as well as nodular
aggregates of T cells, B cells, and plasma cells in the adventitia of affected
arteries. These findings further endorse the role of specific cellular and
humoral immunity in Kawasaki disease. Unremitting coronary arteritis and
excessive smooth muscle hyperplasia resulted in coronary occlusion despite the
use of cyclosporin A. N.
Ref:: 37
----------------------------------------------------
[7]
TÍTULO / TITLE: - Donor-specific
tolerance in fully major histocompatibility major histocompatibility
complex-mismatched limb allograft transplants under an anti-alphabeta T-cell
receptor monoclonal antibody and cyclosporine A protocol.
REVISTA
/ JOURNAL: - Transplantation 2003 Dec 27;76(12):1662-8.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000105343.49626.6F
AUTORES
/ AUTHORS: - Siemionow MZ; Izycki DM; Zielinski M
INSTITUCIÓN
/ INSTITUTION: - Department of Plastic Surgery, Cleveland
Clinic Foundation, A60, 9500 Euclid Avenue, Cleveland, OH 44195, USA. siemiom@ccf.org
RESUMEN
/ SUMMARY: - BACKGROUND: Recent studies have
demonstrated that treatment with alphabeta-T-cell receptor (TCR) monoclonal
antibody and cyclosporine A (CsA) can extend survival in composite tissue
allografts (CTA). The purpose of this study was to induce tolerance in fully
major histocompatibility complex (MHC)-mismatched rat limb allografts under 7
days of a combined alphabeta-TCR-CsA protocol. METHODS: The authors performed
30 hind-limb allotransplantations across the MHC barrier between Brown Norway
donors (BN; RT1n) and Lewis recipients (LEW; RT1l). Isograft and allograft
controls received no treatment. The experimental groups received monotherapy of
alphabeta-TCR and CsA or a combination of alphabeta-TCR and CsA for 7 days
only. Donor-specific tolerance and immunocompetence were determined by standard
skin grafting in vivo and mixed lymphocyte reaction (MLR) in vitro. The
efficacy of immunosuppressive therapy and the level of donor-specific chimerism
were determined by flow cytometry. RESULTS: Long-term survival (>350 days)
was achieved in allograft recipients (n=6) under the 7-day protocol of combined
alphabeta-TCR-CsA. Donor-specific tolerance and immunocompetence of long-term
chimeras were confirmed by acceptance of skin grafts from the donors and
rejection of the third-party alloantigens (AxC Irish). At day 120, MLR
demonstrated unresponsiveness to the host and donor antigens but strong
reactivity against third-party alloantigens. Flow cytometry confirmed the high
efficacy of immunosuppressive treatment and the development of donor-specific
chimerism (7.6% of CD4+-RT1n+ cells, 1.3% of CD8+-RT1n+ cells, and 16.5% of
CD45RA+-RT1n+ cells) in the periphery of tolerated recipients. CONCLUSIONS:
Combined therapy of alphabeta-TCR-CsA for 7 days resulted in tolerance induction
in fully MHC-mismatched rat hind-limb allografts. Tolerance was directly
associated with stable, donor-specific chimerism.
----------------------------------------------------
[8]
TÍTULO / TITLE: - Posttransplantation
diabetes: a systematic review of the literature.
REVISTA
/ JOURNAL: - Diabetes Care. Acceso gratuito al texto
completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://care.diabetesjournals.org/
●●
Cita: Diabetes Care: <> 2002 Mar;25(3):583-92.
AUTORES
/ AUTHORS: - Montori VM; Basu A; Erwin PJ; Velosa JA;
Gabriel SE; Kudva YC
INSTITUCIÓN
/ INSTITUTION: - Division of Endocrinology, Diabetes,
Metabolism, Nutrition, and Internal Medicine, Mayo Clinic, Rochester, Minnesota
55905, USA.
RESUMEN
/ SUMMARY: - OBJECTIVES: To systematically review the
incidence of posttransplantation diabetes (PTD), risk factors for its
development, prognostic implications, and optimal management. RESEARCH DESIGN
AND METHODS: We searched databases (MEDLINE, EMBASE, the Cochrane Library, and
others) from inception to September 2000, reviewed bibliographies in reports
retrieved, contacted transplantation experts, and reviewed specialty journals.
Two reviewers independently determined report inclusion (original studies, in
all languages, of PTD in adults with no history of diabetes before transplantation),
assessed study methods, and extracted data using a standardized form.
Meta-regression was used to explain between-study differences in incidence.
RESULTS: Nineteen studies with 3,611 patients were included. The 12-month
cumulative incidence of PTD is lower (<10% in most studies) than it was 3
decades ago. The type of immunosuppression explained 74% of the variability in
incidence (P = 0.0004). Risk factors were patient age, nonwhite ethnicity,
glucocorticoid treatment for rejection, and immunosuppression with high-dose
cyclosporine and tacrolimus. PTD was associated with decreased graft and
patient survival in earlier studies; later studies showed improved outcomes.
Randomized trials of treatment regimens have not been conducted. CONCLUSIONS:
Physicians should consider modification of immunosuppressive regimens to
decrease the risk of PTD in high-risk transplant recipients. Randomized trials
are needed to evaluate the use of oral glucose-lowering agents in transplant
recipients, paying particular attention to interactions with immunosuppressive
drugs. N. Ref:: 79
----------------------------------------------------
[9]
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
----------------------------------------------------
[10]
TÍTULO / TITLE: - Mycophenolate mofetil
for the prevention and treatment of graft-versus-host disease following stem
cell transplantation: preliminary findings.
REVISTA
/ JOURNAL: - Bone Marrow Transplant 2001
Jun;27(12):1255-62.
AUTORES
/ AUTHORS: - Vogelsang GB; Arai S
INSTITUCIÓN
/ INSTITUTION: - Department of Oncology, Johns Hopkins
Oncology Center, Baltimore, MD 21287-8943, USA.
RESUMEN
/ SUMMARY: - The therapeutic benefits of allogeneic
stem cell transplantation in patients with hematologic disorders are limited by
the significant morbidity and mortality of graft-versus-host disease (GVHD).
Current agents for the prevention and treatment of GVHD have limited efficacy
and often result in toxic side-effects. Mycophenolate mofetil (MMF) is a new
immunosuppressant with a selective mechanism of action. When employed following
solid organ transplantation, MMF reduces the incidence and severity of acute
rejection episodes. By selectively targeting activated lymphocytes, the active
metabolite of MMF, mycophenolic acid (MPA), appears to augment the actions of
standard immunosuppressant agents without adding overlapping toxicities.
Studies of combination regimens that include MMF report that this agent permits
a dose reduction of cyclosporine, tacrolimus, or corticosteroid, without
increasing the incidence of acute rejection in solid organ transplants. Reports
on the efficacy of MMF following stem cell transplantation in animal studies
were mixed. However, the use of a non-myeloablative conditioning regimen with a
post-graft immunosuppressive regimen of MMF and cyclosporine was able to
sustain stable mixed chimeras in 60% to 80% of dogs who received hematopoietic
grafts from DLA-identical littermates. MMF has demonstrated activity in
preliminary clinical trials for GVHD prophylaxis, and treatment of acute or
chronic GVHD. Larger clinical trials are warranted to determine the optimum
dose and route of MMF administration for GVHD, as well as the comparative
safety and efficacy of MMF-containing regimens. N. Ref:: 36
----------------------------------------------------
[11]
TÍTULO / TITLE: - CD30+ T-cell lymphoma
in a patient with psoriasis treated with ciclosporin and infliximab.
REVISTA
/ JOURNAL: - Br J Dermatol 2003 Jul;149(1):170-3.
AUTORES
/ AUTHORS: - Mahe E; Descamps V; Grossin M; Fraitag S;
Crickx B
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology, Bichat-Claude
Bernard Hospital, 46 Rue Henri-Huchard, Paris Cedex 18, France. emmanuel.mahe@bch.ap-hop-paris.fr
RESUMEN
/ SUMMARY: - There is a known relationship between the
use of immunosuppressive therapies and the development of lymphoproliferative
malignancies. These lymphomas are mainly B-cell nonHodgkin’s lymphomas
associated with Epstein-Barr virus. Most cases concern classical
immunosuppressive treatments including ciclosporin and methotrexate. A
relationship between the new antitumour necrosis factor (TNF)-alpha agents and
lymphoproliferative malignancies is debated. Patients with psoriasis on immunosuppressive
therapies, mainly ciclosporin, are considered to have a low risk of developing
lymphoid proliferation. We report a patient with erythrodermic psoriasis
treated with ciclosporin and infliximab who developed a CD30+ T-cell lymphoma.
This lymphoma regressed after stopping these treatments. In this case, the
anti-TNF-alpha agent may have played a role in association with ciclosporin in
the development of the lymphoproliferative disorder. Whereas the combination of
anti-TNF-alpha therapies with methotrexate has been well studied, their
combination with ciclosporin has been evaluated only in a few patients.
Psoriatic patients who may require anti-TNF-alpha treatment have often been or
will be treated with ciclosporin. The combination of ciclosporin and anti-TNF-alpha
warrants further investigation. N.
Ref:: 17
----------------------------------------------------
[12]
TÍTULO / TITLE: - European best practice
guidelines for renal transplantation. Section IV: Long-term management of the
transplant recipient. IV.5.8. Cardiovascular risks. Immunosuppressive therapy.
REVISTA
/ JOURNAL: - Nephrol Dial Transplant. Acceso gratuito
al texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://ndt.oupjournals.org/
●●
Cita: Nephrology Dialysis Transplantation: <> 2002;17 Suppl 4:30-1.
RESUMEN
/ SUMMARY: - GUIDELINE: Immunosuppressive therapies,
especially corticosteroids and anticalcineurin inhibitors; contribute to the
prevalence of cardiovascular risk factors, such as arterial hypertension,
hyperlipidaemia and hyperglycaemia, and this effect is dose dependent.
Reduction of the dose, withdrawal and/or switching to another drug could be
useful to control these risk factors.
----------------------------------------------------
[13]
TÍTULO / TITLE: - Multidrug resistance
reversal agents.
REVISTA
/ JOURNAL: - J Med Chem 2003 Nov 6;46(23):4805-17.
●●
Enlace al texto completo (gratuito o de pago) 1021/jm030183a
AUTORES
/ AUTHORS: - Robert J; Jarry C
INSTITUCIÓN
/ INSTITUTION: - Institut Bergonie, 229, Cours de
l’Argonne, 33076 Bordeaux Cedex, France. robert@bergonie.org N. Ref:: 151
----------------------------------------------------
[14]
TÍTULO / TITLE: - Review article: the
risk of lymphoma associated with inflammatory bowel disease and immunosuppressive
treatment.
REVISTA
/ JOURNAL: - Aliment Pharmacol Ther 2001
Aug;15(8):1101-8.
AUTORES
/ AUTHORS: - Aithal GP; Mansfield JC
INSTITUCIÓN
/ INSTITUTION: - Department of Gastroenterology, University
of Newcastle, Newcastle upon Tyne, UK.
RESUMEN
/ SUMMARY: - Lymphoma complicating inflammatory bowel
disease is well described. Whether the risk of lymphoma is increased by
immunosuppressive treatment with azathioprine, 6-mercaptopurine or infliximab
is a common concern among patients and physicians considering using these
agents. This review aims to quantify the lymphoma risk in inflammatory bowel
disease and the added risk attributable to these treatments. The evidence from
published cases is that lymphomas occur at sites of active inflammatory bowel disease
more often than expected for this to be a chance association. Studies on
inflammatory bowel disease populations are conflicting, with some follow-up
studies from large inflammatory bowel disease clinics showing an increase in
lymphoma incidence, while other population-based studies show little or no
increase in risk of lymphoma. A small increase in lymphoma risk in inflammatory
bowel disease, perhaps 2-3-fold, may be compatible with both sets of data.
Studies of the risks associated with immuno- suppression are less satisfactory,
with smaller numbers of patients and relatively short follow-up. The available
evidence would support a further increase in lymphoma risk associated with
immunosuppressive treatment in inflammatory bowel disease of around fivefold
compared to no immunosuppressive use, and tenfold compared to the general
population. The risks appear to be less than that associated with renal and
hepatic transplant-related immunosuppression. Infliximab treatment is still too
new to make a full assessment of its long-term safety, but post-marketing
surveillance currently suggests that lymphoma risk may not be any greater than
that associated with azathioprine and 6-mercaptopurine. Population-wide
surveillance for lymphoma in inflammatory bowel disease would be required to
narrow the confidence intervals on these estimates of lymphoma risk in
inflammatory bowel disease and immunosuppressive treatment. N. Ref:: 54
----------------------------------------------------
[15]
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
----------------------------------------------------
[16]
TÍTULO / TITLE: - New immunosuppressive
agent: expectations and controversies.
REVISTA
/ JOURNAL: - Transplantation 2003 Mar 27;75(6):741-2.
AUTORES
/ AUTHORS: - Alsina J; Grinyo JM
INSTITUCIÓN
/ INSTITUTION: - Department of Nephrology, Bellvitge
Hospital, Barcelona, España. N.
Ref:: 5
----------------------------------------------------
[17]
TÍTULO / TITLE: - How should the
immunosuppressive regimen be managed in patients with established chronic
allograft failure?
REVISTA
/ JOURNAL: - Kidney Int Suppl 2002 May;(80):68-72.
AUTORES
/ AUTHORS: - Danovitch GM
INSTITUCIÓN
/ INSTITUTION: - Division of Nephrology, UCLA School of
Medicine, USA. gdanovitch@mednet.ucla.edu N. Ref:: 25
----------------------------------------------------
[18]
TÍTULO / TITLE: - Graft vascular function
after transplantation of pancreatic islets.
REVISTA
/ JOURNAL: - Diabetologia 2002 Jun;45(6):749-63. Epub
2002 May 15.
●●
Enlace al texto completo (gratuito o de pago) 1007/s00125-002-0827-4
AUTORES
/ AUTHORS: - Jansson L; Carlsson PO
INSTITUCIÓN
/ INSTITUTION: - Department of Medical Cell Biology,
Biomedical Center, Uppsala University, Box 571, 751 23 Uppsala, Sweden. Leif.Jansson@medcellbiol.uu.se
RESUMEN
/ SUMMARY: - Endogenous pancreatic islets have a dense
glomerular-like angioarchitecture, which ensures an optimal delivery of oxygen
and nutrients to the islet cells, provides signals from other cells in the body
and disposes secreted hormones. Transplantation of isolated islets means that
their vascular connection is interrupted. The islet grafts therefore depend
upon endothelial cells and microvessels originating in the implantation organ
for derivation of a new vascular system. A re-establishment of islet blood-flow
occurs within 7-14 days after transplantation, mainly through vascular
sprouting. The newly formed blood vessels acquire the morphological
characteristics of those in endogenous islets. In intraportally transplanted
islets to the liver, the islets become revascularized almost exclusively from
tributaries to the hepatic artery. Exocrine contamination of the transplanted
islets could hamper the revascularization process, whereas neither
cryopreservation nor immunosuppressive drugs like cyclosporin, prednisolon and
RS-61443 have any essential effects on the angiogenesis. Investigators have noticed
improvements in islet graft survival and function by means of basic fibroblast
growth factor (bFGF), acidic FGF and endothelial cell growth factor exposure of
the grafts. The functional properties of transplanted islets are largely
unknown, but evidence from experimental islet transplantation suggests that
both the blood perfusion and the tissue oxygen tension of the grafted islets
are chronically decreased, indicating an insufficient vascular system. In order
to achieve optimal condition for survival and function of transplanted beta
cells, it is important to ascertain whether impairments in vascular function
are present also after clinical islet transplantations as well. N. Ref:: 181
----------------------------------------------------
[19]
TÍTULO / TITLE: - Is there still a role
for cyclosporine in the treatment of inflammatory bowel disease? Pro argument.
REVISTA
/ JOURNAL: - Inflamm Bowel Dis 2003 May;9(3):194-7;
discussion 202-4.
AUTORES
/ AUTHORS: - Kornbluth A
INSTITUCIÓN
/ INSTITUTION: - The Mount Sinai Medical Center, New York,
New York, USA. akornbluth@aol.com N. Ref:: 32
----------------------------------------------------
[20]
TÍTULO / TITLE: - Is there still a role
for cyclosporine in the treatment of inflammatory bowel disease? Con argument.
REVISTA
/ JOURNAL: - Inflamm Bowel Dis 2003 May;9(3):198-201;
discussion 202-4.
AUTORES
/ AUTHORS: - Fellermann K; Luhmann D; Stange EF
INSTITUCIÓN
/ INSTITUTION: - Department of Internal Medicine I, Robert-Bosch-Krankenhaus,
Stuttgart, Germany. klaus.fellermann@rbk.de N. Ref:: 21
----------------------------------------------------
[21]
TÍTULO / TITLE: - TOR inhibitors and
cardiac allograft vasculopathy: is inhibition of intimal thickening an adequate
surrogate of benefit?
REVISTA
/ JOURNAL: - J Heart Lung Transplant 2003
May;22(5):501-4.
AUTORES
/ AUTHORS: - Mehra MR; Uber PA
INSTITUCIÓN
/ INSTITUTION: - Cardiomyopathy and Heart Transplantation
Center, Ochsner Clinic Foundation, New Orleans, Louisiana 70121, USA. mmehra@ochsner.org N. Ref:: 30
----------------------------------------------------
[22]
TÍTULO / TITLE: - European best practice
guidelines for renal transplantation. Section IV: Long-term management of the
transplant recipient. IV.3.1 Long-term immunosuppression. Late steroid or
cyclosporine withdrawal.
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 4:19-20.
RESUMEN
/ SUMMARY: - GUIDELINES: A. In order to reduce or avoid
long-term serious adverse effects of corticosteroids, such as bone fractures,
diabetes mellitus, arterial hypertension, osteoporosis and eye complications,
steroid withdrawal should be considered. B. Steroid withdrawal is safe only in
a proportion of graft recipients and is recommended only in low-risk patients.
The efficacy of the remaining immunosuppression should be considered. C. After
steroid withdrawal, graft function has to be monitored very carefully because
of the risk of a delayed but continuous loss of function due to chronic graft
dysfunction. In the case of functional deterioration or dysfunction, steroids
should be re-administered. D. Cyclosporine withdrawal might be considered in
order to ameliorate nephrotoxicity, arterial hypertension, lipid disorders and
hypertrichosis. This can be carried out with no significant long-term risk of
progressive graft loss. The efficacy of the remaining immunosuppression should
be considered. After cyclosporine withdrawal, careful monitoring for acute
rejection is recommended.
----------------------------------------------------
[23]
TÍTULO / TITLE: - Steroid-resistant
kidney transplant rejection: diagnosis and treatment.
REVISTA
/ JOURNAL: - J Am Soc Nephrol. Acceso gratuito al texto
completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.jasn.org/
●●
Cita: Journal of the American Society of Nephrology: <> 2001 Feb;12 Suppl
17:S48-52.
AUTORES
/ AUTHORS: - Bock HA
INSTITUCIÓN
/ INSTITUTION: - Division of Nephrology, Kantonsspital,
Aarau, Switzerland. bock@ksa.ch
RESUMEN
/ SUMMARY: - Decreases in transplant function may be
attributable to a variety of conditions, including prerenal and postrenal
failure, cyclosporin A (CsA) toxicity, polyoma nephritis, recurrent
glomerulonephritis, and rejection. The diagnosis of rejection should therefore
be made on the basis of a transplant biopsy of adequate size, before the
initiation of any therapy. Pulse steroid treatment (three to five 0.25- to
1.0-g pulses of methylprednisolone, administered intravenously) is the usual
first-line therapy and has a 60 to 70% success rate, although orally
administered prednisone (0.25 g) may be just as efficacious. Even if reverted,
any rejection should trigger an at least temporary increase in basal
immunosuppression, consisting of an increase in CsA or tacrolimus target
levels, the addition of steroids or an increase in their dosage, the addition
of mycophenolate mofetil, or a switch from CsA to tacrolimus. The addition of
rapamycin or its RAD derivative may fulfill the same purpose. Steroid
resistance should not be assumed before the fifth day of pulse steroid
treatment, although histologic features of vascular rejection may indicate the
need for more aggressive treatment earlier. Steroid-resistant rejection is
traditionally treated with poly- or monoclonal antilymphocytic antibodies, with
success rates of 60 to 70%. Their potential benefit must be carefully balanced
against the risks of infection and lymphoma. More recently, mycophenolate
mofetil has been successfully used to treat steroid-resistant rejection, but
only of the interstitial (cellular) type. Switching from CsA to tacrolimus for
treating recurrent or antibody-resistant rejection is successful in
approximately 60% of cases. Plasmapheresis and intravenously administered Ig
have been used in some desperate cases, with surprising success. Because none
of the available drugs has a significantly better profile of therapeutic versus
adverse effects, the possible benefits of continued rejection therapy must be
continuously balanced with the potential for serious, sometimes fatal, side
effects. N. Ref:: 35
----------------------------------------------------
[24]
TÍTULO / TITLE: - ATP-binding cassette
transporters and calcineurin inhibitors: potential clinical implications.
REVISTA
/ JOURNAL: - Transplant Proc 2001 May;33(3):2420-1.
AUTORES
/ AUTHORS: - van Gelder T; Klupp J; Sawamoto T;
Christians U; Morris RE
INSTITUCIÓN
/ INSTITUTION: - Department of Internal Medicine (T.vG.),
University Hospital Rotterdam, Rotterdam, The Netherlands. vangelder@INW1.AZR.NL N. Ref:: 17
----------------------------------------------------
[25]
TÍTULO / TITLE: - Immunosuppression and
transplant vascular disease: benefits and adverse effects.
REVISTA
/ JOURNAL: - Pharmacol Ther 2003 Nov;100(2):141-56.
AUTORES
/ AUTHORS: - Moien-Afshari F; McManus BM; Laher I
INSTITUCIÓN
/ INSTITUTION: - Department of Pharmacology and
Therapeutics, Faculty of Medicine, University of British Columbia, 2176 Health
Sciences Mall, Vancouver, BC Canada V6T 1Z3.
RESUMEN
/ SUMMARY: - Cardiac allograft vasculopathy (CAV)
occurs within 5 years of transplantation surgery and represents the main cause
of death in long-term heart transplant survivors. The detailed pathogenesis of
CAV is unknown, but there are strong indications that immunologic mechanisms,
which are regulated by nonimmunologic factors, are the major cause of this
phenomenon. Cyclosporine A (CsA) is a frequently used immunosuppressive agent
in transplant medicine to prevent rejection. The mechanism of action of CsA
involves initial binding to cyclophilin to form a complex that then inhibits
calcineurin (CN), leading to reduced interleukin (IL)-2 production as part of
the signal transduction pathway for the activation of B-lymphocytes and
T-lymphocytes. Based on this proposed mechanism, it was expected that CsA
should be an effective strategy in attenuating the host immune response against
transplanted allograft tissue; however, CsA has not changed the outcome of CAV.
Several mechanisms have been suggested for the ineffectiveness of CsA in
long-term prevention of CAV. For example, routine therapeutic doses of CsA may
block CN incompletely (50%), whereas complete blockade requires doses that are
not clinically tolerable. Another explanation is the possible activation of
T-cell receptors directly (CN independent) by the immune response, which
induces protein kinase C theta (PKCtheta) and leads to IL-2 production and
immune rejection. Moreover, there may be a role for nonimmunologic mechanisms,
such as complement, which cannot be controlled by CsA, or CsA may cause
hypercholesterolemia or induce overexpression of transforming growth
factor-beta (TGF-beta). This review also compares the effect of CsA with other
immunosuppressants in allograft artery preservation and their clinical
efficacy. N. Ref:: 192
----------------------------------------------------
[26]
- Castellano -
TÍTULO / TITLE:Leucoencefalopatia posterior
reversible en un paciente con linfoma no-Hodgkin tras tratamiento con CHOP.
Reversible posterior leukoencephalopathy in a patient with non-Hodgkin’s
lymphoma after treatment with CHOP.
REVISTA
/ JOURNAL: - An Med Interna 2001 Nov;18(11):591-3.
AUTORES
/ AUTHORS: - Gimenez-Mesa E; Martinez-Salio A;
Porta-Etessam J; Berbel Garcia A; Cedena Romero T; Salama Bendoyan P
INSTITUCIÓN
/ INSTITUTION: - Servicio de Neurologia, Hospital
Universitario Doce de Octubre, Ctra de Andalucia km 5,400, 28041 Madrid.
RESUMEN
/ SUMMARY: - Reversible posterior leukoencephalopathy
syndrome is a newly characterised and increasingly recognized
clinico-radiologic syndrome. Underlying conditions that reportedly trigger this
syndrome include hypertensive encephalopathy, eclampsia, renal failure, and
immunosuppressive drug therapy with cyclosporine, tacrolimus and interferon
alpha. We describe a 51-year-old woman with non-Hodgkin’s lymphoma treated with
conventional CHOP chemotherapy. Eight days after this treatment she developed
severe headache, bilateral visual loss and focal seizures with secondary
generalization. Neurologic examination showed confusion, cortical blindness,
and left hemiparesis with hyperreflexia and sensory loss. A cranial T2-weighted
magnetic resonance imaging revealed increased signal intensity in the occipital
and frontal lobes in both hemispheres and right parietal lobe. A diagnosis of
reversible posterior leukoencephalopathy was made. She presented a favourable
outcome with conservative treatment with mannitol and phenytoin. A new cranial
scanning showed nearly complete resolution of the abnormalities. To the best of
our knowledge, this is the first case of reversible posterior
leukoencephalopathy in a patient treated with standard-dose CHOP. In this
patient, we confirm the theoretical pathophysiologic mechanisms suggested
explaining how these drugs can cause the syndrome. N. Ref:: 7
----------------------------------------------------
[27]
TÍTULO / TITLE: - FTY720: altered
lymphocyte traffic results in allograft protection.
REVISTA
/ JOURNAL: - Transplantation 2001 Sep 15;72(5):764-9.
AUTORES
/ AUTHORS: - Brinkmann V; Pinschewer DD; Feng L; Chen S
INSTITUCIÓN
/ INSTITUTION: - Novartis Pharma AG, Transplantation
Research, WSJ-386.1.01, CH-4002 Basel, Switzerland. N. Ref:: 52
----------------------------------------------------
[28]
TÍTULO / TITLE: - Alloimmunity and
nonimmunologic risk factors in cardiac allograft vasculopathy.
REVISTA
/ JOURNAL: - Eur Heart J 2003 Jul;24(13):1180-8.
AUTORES
/ AUTHORS: - Vassalli G; Gallino A; Weis M; von Scheidt
W; Kappenberger L; von Segesser LK; Goy JJ
INSTITUCIÓN
/ INSTITUTION: - Division of Cardiology, University
Hospital, Lausanne, Switzerland. gvassall@hospvd.ch
RESUMEN / SUMMARY: - Graft vasculopathy is an accelerated form of coronary artery disease that occurs in transplanted hearts. Despite major advances in immunosuppression, the prevalence of the disease has remained substantially unchanged during the last two decades. According to the ‘response to injury’ paradigm, graft vasculopathy is the result of a continuous inflammatory response to tissue injury initiated by both alloantigen-dependent and independent stress responses. Experimental evidence suggests that these responses may become self-sustaining, as allograft re-transplantation into the donor strain at a later stage fails to prevent disease progression. Histological evidence of endothelitis and arteritis, in association with intima fibrosis and atherosclerosis, reflects the central role of alloimmunity and inflammation in the development of arterial lesions. Experimental results in gene-targeted mouse models indicate that cellular and humoral immune responses are both involved in the pathogenesis of graft vasculopathy. Circulating antibodies against donor endothelium are found in a significant number of patients, but their pathogenic role is still controversial. Alloant