#04#
Revisiones-Clínica-Epidemiología,
Higiene & Prevención *** Reviews-Clinical-Epidemiology, Hygiene &
Prevention
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: - Novel therapeutic
molecular targets for prostate cancer: the mTOR signaling pathway and epidermal
growth factor receptor.
REVISTA
/ JOURNAL: - J Urol 2004 Feb;171(2 Pt 2):S41-3;
discussion S44.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.ju.0000108100.53239.b7
AUTORES
/ AUTHORS: - Tolcher AW
INSTITUCIÓN
/ INSTITUTION: - Director Clinical Research, Institute for
Drug Development Cancer Therapy and Research Center, San Antonio, Texas, USA.
RESUMEN
/ SUMMARY: - PURPOSE: The scientific rationale and
existing evidence for the use of novel molecular targets in the chemoprevention
of cancer are reviewed, with special attention to prostate cancer. MATERIALS
AND METHODS: A search for relevant literature on basic science and clinical
trials was conducted using PubMed/MEDLINE. RESULTS: The emergence of
molecularly targeted therapies for advanced malignancies creates an important
opportunity to examine these agents for the chemoprevention of prostate cancer.
Two critical targets in the proliferation and malignant transformation of
normal cells, the PI3/Akt signal transduction pathway and the epidermal growth
factor receptor, are currently the focus of several novel investigational
therapies that are in late stage phase II and phase III studies. CONCLUSIONS:
Research to date supports consideration of these novel molecular targets as
future agents in the chemoprevention of prostate cancer. N. Ref:: 28
----------------------------------------------------
[3]
TÍTULO / TITLE: - Drug-eluting stents in
vascular intervention.
REVISTA
/ JOURNAL: - Lancet 2003 Jan 18;361(9353):247-9.
AUTORES
/ AUTHORS: - Fattori R; Piva T
INSTITUCIÓN
/ INSTITUTION: - Department of Radiology, Cardiovascular
Unit, University Hospital S Orsola, 40138, Bologna, Italy. ross@med.unibo.it
RESUMEN
/ SUMMARY: - CONTEXT: Restenosis is the most important
long-term limitation of stent implantation for coronary artery disease,
occurring in 15-60% of patients. In-stent restenosis, a refractory coronary
lesion resulting from neointimal hyperplasia, challenges both vascular
biologist and interventional cardiologist. Various drugs and devices have been
used tried to overcome restenosis but are not particularly successful. Over
1500000 percutaneous coronary interventions are done annually. Restenosis is
not only important clinically but also for its impact on health-care costs.
STARTING POINT: Growth and migration of vascular smooth-muscle cells result in
neointimal proliferation after vascular injury and are the key mechanism of
in-stent restenosis. The rationale of the most recent approaches to restenosis
(eg, brachytherapy and immunosuppressive agents) arises from the similarity
between tumour-cell growth and the benign tissue proliferation which
characterises intimal hyperplasia. Several immunosuppressants have been tested
for their potential to inhibit restenosis, with the novel strategy of
administering the drug via a coated stent platform. Local drug delivery
achieves higher tissue concentrations of drug without systemic effects, at a
precise site and time. The first multicentre trial with stents coated with
sirolimus was by Marie-Claude Morice and colleagues (N Engl J Med 2002; 346:
1773-80). In a trial of 238 patients, restenosis of 50% or more at 6 months was
0% and 27% with sirolimus or normal stents (p<0.001), respectively, after
percutaneous revascularisation. Muzaffer Degertekin and colleagues (Circulation
2002; 106: 1610-13) present data on 2-year follow-up of 15 patients who had
been implanted with the sirolimus stent in another study, and confirm
persistent inhibition of restenosis and an absence of unexpected adverse
events. WHERE NEXT? Local application of antiproliferative agents is a
promising technique and research is developing. Other agents with potential
benefits (eg, statins, local gene-therapy, adenovirus-mediated arterial
gene-transfer, L-arginine, abciximab, angiopeptin, recombinant pegylated
hirudin, and hiloprost) as well as improvements in polymer technology
(biodegradable smart polymers, coatings for multiple-drug release) are under
evaluation. The clinical impact of the elimination of restenosis may influence
the approach to coronary artery disease, the future of cardiac surgery, and
health-care economics in cardiology. N.
Ref:: 22
----------------------------------------------------
[4]
TÍTULO / TITLE: - Treatment of chronic
granulomatous disease with myeloablative conditioning and an unmodified
hemopoietic allograft: a survey of the European experience, 1985-2000.
REVISTA
/ JOURNAL: - Blood. Acceso gratuito al texto completo a
partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.bloodjournal.org/
●●
Cita: Blood: <> 2002 Dec 15;100(13):4344-50. Epub 2002 Aug 8.
●●
Enlace al texto completo (gratuito o de pago) 1182/blood-2002-02-0583
AUTORES
/ AUTHORS: - Seger RA; Gungor T; Belohradsky BH;
Blanche S; Bordigoni P; Di Bartolomeo P; Flood T; Landais P; Muller S; Ozsahin
H; Passwell JH; Porta F; Slavin S; Wulffraat N; Zintl F; Nagler A; Cant A;
Fischer A
INSTITUCIÓN
/ INSTITUTION: - European Group for Blood and Marrow
Transplantation (EBMT) and the European Society for Immunodeficiencies (ESID),
Division of Immunology/Hematology, University Children’s Hospital, Zurich,
Switzerland. reinhard.seger@kispi.unizh.ch
RESUMEN
/ SUMMARY: - Treatment of chronic granulomatous disease
(CGD) with myeloablative bone marrow transplantation is considered risky. This
study investigated complications and survival according to different risk
factors present at transplantation. The outcomes of 27 transplantations for
CGD, from 1985 to 2000, reported to the European Bone Marrow Transplant
Registry for primary immunodeficiencies were assessed. Most transplant
recipients were children (n = 25), received a myeloablative busulphan-based
regimen (n = 23), and had unmodified marrow allografts (n = 23) from human
leukocyte antigen (HLA)-identical sibling donors (n = 25). After myeloablative
conditioning, all patients fully engrafted with donor cells; after
myelosuppressive regimens, 2 of 4 patients fully engrafted. Severe (grade 3 or
4) graft-versus-host disease (GVHD) disease developed in 4 patients: 3 of 9
with pre-existing overt infection, 1 of 2 with acute inflammatory disease.
Exacerbation of infection during aplasia was observed in 3 patients;
inflammatory flare at the infection site during neutrophil engraftment in 2:
all 5 patients belonged to the subgroup of 9 with pre-existing infection.
Overall survival was 23 of 27, with 22 of 23 cured of CGD (median follow-up, 2
years). Survival was especially good in patients without infection at the
moment of transplantation (18 of 18). Pre-existing infections and inflammatory
lesions have cleared in all survivors (except in one with autologous
reconstitution). Myeloablative conditioning followed by transplantation of
unmodified hemopoietic stem cells, if performed at the first signs of a severe
course of the disease, is a valid therapeutic option for children with CGD
having an HLA-identical donor. N.
Ref:: 30
----------------------------------------------------
[5]
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.
----------------------------------------------------
[6]
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
----------------------------------------------------
[7]
TÍTULO / TITLE: - Calcineurin inhibition
and cardiac hypertrophy: a matter of balance.
REVISTA
/ JOURNAL: - Proc Natl Acad Sci U S A. Acceso gratuito
al texto completo a partir de los 6 meses de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.pnas.org/
●●
Cita: Proc Natl Acad Sci USA (PNAS): <> 2001 Mar 13;98(6):2947-9.
●●
Enlace al texto completo (gratuito o de pago) 1073/pnas.051033698
AUTORES
/ AUTHORS: - Leinwand LA
INSTITUCIÓN
/ INSTITUTION: - Department of Molecular, Cellular, and
Developmental Biology, Porter Addition, Room A3B40, University of Colorado,
Boulder, CO 80309-0347, USA. leinwand@stripe.colorado.edu N. Ref:: 18
----------------------------------------------------
[8]
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
----------------------------------------------------
[9]
TÍTULO / TITLE: - Prevention by dietary
(n-6) polyunsaturated phosphatidylcholines of intrahepatic cholestasis induced
by cyclosporine A in animals.
REVISTA
/ JOURNAL: - Life Sci 2003 Jun 13;73(4):381-92.
AUTORES
/ AUTHORS: - Chanussot F; Benkoel L
INSTITUCIÓN
/ INSTITUTION: - INSERM U. 476, Faculte de Medecine, 27 bd
Jean Moulin, 13385 Marseille cedex 05, France. Francoise.Chanussot@medecine.univ-mrs.fr
RESUMEN
/ SUMMARY: - Previous findings showed that dietary
(n-6) polyunsaturated phosphatidylcholines (vegetable lecithin) could
efficiently prevent intrahepatic cholestasis induced by cyclosporine A in rats.
Mechanistic studies showed that expressions in rat liver of Na(+), K(+)-ATPase,
Ca(2+), Mg(2+)-ATPase and F-actin were both decreased by drug administration
and both enhanced by (n-6) lecithin enriched diet. There is a possible direct
effect of phosphatidylcholines, vectors of polyunsaturated fatty acids provided
by the metabolism of the dietary lecithin, on the aforesaid hepatic parameters.
Such modulations by drug and diet result in reversed modifications of membrane
composition and fluidity. Final outcome is decreased and enhanced bile lipid
secretion by cyclosporine and vegetable lecithin enriched diet respectively.
Moreover, we advance the hypothesis of a bypass process including a separate
and functional actin-independent way for the non micellar and
phospholipid-dependent secretion of bile lipids. The relationships between the
ATPases, the microfilament components such as F-actin and the different
transporters still remain to be clarified. Furthermore, one can speculate on
beneficial effects in humans of diets enriched in vegetable lecithins that
might prevent cholestasis induced by cyclosporine A. N. Ref:: 75
----------------------------------------------------
[10]
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
----------------------------------------------------
[11]
TÍTULO / TITLE: - Drug-eluting stents and
glycoprotein IIb/IIIa inhibitors: combination therapy for the future.
REVISTA
/ JOURNAL: - Am Heart J 2003 Oct;146(4 Suppl):S13-7.
●●
Enlace al texto completo (gratuito o de pago) 1016/j.ahj.2003.09.004
AUTORES
/ AUTHORS: - Leon MB; Bakhai A
RESUMEN
/ SUMMARY: - BACKGROUND: Although coronary stenting has
improved the results of coronary interventions compared to coronary angioplasty
alone, in-stent restenosis remains a significant limitation of this procedure.
Drug-eluting stents with or without glycoprotein IIb/IIIa inhibitor therapy
represent an additional advance in the evolution of this strategy. METHODS: We
review the currently available trials comparing studies of non-drug-eluting and
drug-eluting stents using sirolimus and paclitaxel agents and their
derivatives. RESULTS: Ten studies are available that compare drug-eluting to
traditional non-drug-eluting stents. A variety of antiplatelet regimes have
been used. The majority of these studies are in the process of being published.
No head-to-head studies comparing different drug-eluting stents are available.
CONCLUSIONS: Drug-eluting stents using sirolimus and paclitaxel in combination
with enhanced antiplatelet strategies represent an important advantage over
non-drug-eluting stents for the reduction of in-stent restenosis. The rate at
which drug-eluting stents are adapted into widespread practice depends heavily
on whether they are safe, efficacious, and cost-effective in various clinical
settings. N. Ref:: 28
----------------------------------------------------
[12]
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
----------------------------------------------------
[13]
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
----------------------------------------------------
[14]
TÍTULO / TITLE: - Basiliximab: a review
of its use as induction therapy in renal transplantation.
REVISTA
/ JOURNAL: - Drugs 2003;63(24):2803-35.
AUTORES
/ AUTHORS: - Chapman TM; Keating GM
INSTITUCIÓN
/ INSTITUTION: - Adis International Limited, Auckland, New
Zealand. demail@adis.co.nz
RESUMEN
/ SUMMARY: - Basiliximab (Simulect), a chimeric
(human/murine) monoclonal antibody, is indicated for the prevention of acute
organ rejection in adult and paediatric renal transplant recipients in
combination with other immunosuppressive agents.Basiliximab significantly
reduced acute rejection compared with placebo in renal transplant recipients
receiving dual- (cyclosporin microemulsion and corticosteroids) or
triple-immunotherapy (azathioprine- or mycophenolate mofetil-based); graft and
patient survival rates at 12 months were similar. Significantly more basiliximab
than placebo recipients were free from the combined endpoint of death, graft
loss or acute rejection 3 years, but not 5 years, after transplantation.The
incidence of adverse events was similar in basiliximab and placebo recipients,
with no increase in the incidence of infection, including cytomegalovirus (CMV)
infection. Malignancies or post-transplant lymphoproliferative disorders after
treatment with basiliximab were rare, with a similar incidence to that seen
with placebo at 12 months or 5 years post-transplantation. Rare cases of
hypersensitivity reactions to basiliximab have been reported.The efficacy of
basiliximab was similar to that of equine antithymocyte globulin (ATG) and
daclizumab, and similar to or greater than that of muromonab CD3. Basiliximab
was as effective as rabbit antithymocyte globulin (RATG) in patients at
relatively low risk of acute rejection, but less effective in high-risk
patients. Numerically or significantly fewer patients receiving basiliximab
experienced adverse events considered to be related to the study drug than ATG
or RATG recipients. The incidence of infection, including CMV infection, was
similar with basiliximab and ATG or RATG.Basiliximab plus baseline
immunosuppression resulted in no significant differences in acute rejection
rates compared with baseline immunosuppression with or without ATG or
antilymphocyte globulin in retrospective analyses conducted for small numbers
of paediatric patients. Limited data from paediatric renal transplant
recipients suggest a similar tolerability profile to that in adults.
Basiliximab appears to allow the withdrawal of corticosteroids or the use of
corticosteroid-free or calcineurin inhibitor-sparing regimens in renal
transplant recipients.Basiliximab did not increase the overall costs of therapy
in pharmacoeconomic studies.CONCLUSION: Basiliximab reduces acute rejection
without increasing the incidence of adverse events, including infection and
malignancy, in renal transplant recipients when combined with standard dual- or
triple-immunotherapy. The overall incidence of death, graft loss or acute
rejection was significantly reduced at 3 years; there was no significant
difference for this endpoint 5 years after transplantation. Malignancy was not
increased at 5 years. The overall efficacy, tolerability, ease of
administration and cost effectiveness of basiliximab make it an attractive
option for the prophylaxis of acute renal transplant rejection. N. Ref:: 85
----------------------------------------------------
[15]
- Castellano -
TÍTULO / TITLE:La enfermedad linfoproliferativa
difusa postrasplante renal y su relacion con el virus Epstein-Barr. Experiencia
de un centro. Diffuse lymphoproliferative disease after renal transplantation
and its relation with Epstein-Barr virus. Experience at one center.
REVISTA
/ JOURNAL: - Nefrologia. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.aulamedica.es/nefrologia/
●●
Cita: Nefrologia: <> 2002;22(5):463-9.
AUTORES
/ AUTHORS: - Franco A; Jimenez L; Aranda I; Alvarez L;
Gonzalez M; Rocamora N; Olivares J
INSTITUCIÓN
/ INSTITUTION: - Servicio de Nefrologia Hospital General
Alicante Maestro Alonso, 109 03010 Alicante. franco_ant@gva.es
RESUMEN
/ SUMMARY: - Post-transplant lymphoproliferative disorders
(PTLD) are a group of heterogeneous lymphoid proliferations in chronic
immunosuppressed recipients which appear to be related to Epstein Barr Virus
(EBV). Receptor EBV seronegativity, use of antilymphocyte antibodies and CMV
disease have been identified as risk factors that may tigger development of
PTLD. We have studied the incidence of PTLD and its relationship with EBV in
588 adult renal transplant recipients who were transplanted in our hospital
from 1988 to 2001. We have also evaluated the diagnostic and therapeutic
methods used, the risk factors and outcome of the patients who developed PTLD.
We identified 8 recipients (4 males and 4 females), range from 18 to 67 years
(mean age 45.6 years) with a median time between grafting and PTLD of 4.1 years
(0.1-7 years), who developed PTLD (1.3%). Only 1 patient received OKT3 and had
CMV disease, two of them (25%) had been treated with hight doses of
prednisolone, another was EBV seronegative, but the rest of them (50%) had no
risk factors. Two patients were diagnosed at autopsy, the diagnosis of 5 was
based on the histology of biopsy and the last one by CT scans of chest-abdomen
and cytology. The presence of EBV in the lymphoproliferative cells was assessed
in 5 out of the 7 studied patients (71.4%). The outcome of our recipients was
poor. Five out of 8 patients died shortly after diagnosis as a direct
consecuence of PTLD and another of an infectious complication of the treatment
(75%). The 2 patients alive started dialysis and 1 of them died 2 years later of
a non-related cause. In conclusion, PTLD is a relatively frequent disease with
a poor prognosis in renal transplant patients. It seems to have a close
relationship with EBV and can develop in the absence of the classical risk
factors. N. Ref:: 18
----------------------------------------------------
[16]
TÍTULO / TITLE: - European best practice
guidelines for renal transplantation. Section IV: Long-term management of the
transplant recipient. IV.10. Pregnancy in renal transplant recipients.
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 4:50-5.
RESUMEN
/ SUMMARY: - GUIDELINES: A. Renal transplantation
restores fertility, and successful pregnancies have been reported in renal
transplant women. In women with normal graft function, pregnancy usually has no
adverse effect on graft function and survival. Therefore, women of childbearing
age who consider pregnancy should receive complete information and support from
the transplant team. B. Pregnancy could be considered safe about 2 years after
transplantation in women with good renal function, without proteinuria, without
arterial hypertension, with no evidence of ongoing rejection and with normal
allograft ultrasound. C. Pregnancy after transplantation should be considered a
high-risk pregnancy and should be monitored by both an obstetrician and the
transplant physician. Pregnancy should be diagnosed as early as possible. The
principal risks are infection, proteinuria, anaemia, arterial hypertension and
acute rejection for the mother, and prematurity and low birth weight for the
foetus. D. Pregnant women and transplanted patients are at increased risk of
infections, especially bacterial urinary tract infections and acute
pyelonephritis of the graft. Urine cultures should be performed monthly and all
asymptomatic infections should be treated. Monitoring of viral infections is
also recommended. (Evidence level B) E. Acute rejection episodes are uncommon
but may occur after delivery. Therefore, immunosuppression should be
re-adjusted immediately after delivery. F. Because pre-eclampsia develops in
30% of pregnant patients, especially those with prior arterial transplant hypertension,
blood pressure, renal function, proteinuria and weight should be monitored
every 2-4 weeks, with more attention during the third trimester.
Anti-hypertensive agents should be changed to those tolerated during pregnancy.
ACE inhibitors and angiotensin II receptor antagonists are absolutely
contra-indicated. G. Immunosuppressive therapy based on cyclosporine or
tacrolimus with or without steroids and azathioprine may be continued in renal
transplant women during pregnancy. Other drugs, such as mycophenolate mofetil
and sirolimus, are not recommended based on current information available.
Because of drug transfer into maternal milk, breastfeeding is not recommended.
H. Vaginal delivery is recommended, but caesarean section is required in at
least 50% of cases. Delivery should occur in a specialized centre. In the
puerperium, renal function, proteinuria, blood pressure,
cyclosporine/tacrolimus blood levels and fluid balance should be closely
monitored.
----------------------------------------------------
[17]
TÍTULO / TITLE: - Cryptococcus neoformans
infection in organ transplant recipients: variables influencing clinical
characteristics and outcome.
REVISTA
/ JOURNAL: - Emerg Infect Dis. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.cdc.gov/
●●
Cita: Emerging Infectious Diseases: <> 2001 May-Jun;7(3):375-81.
AUTORES
/ AUTHORS: - Husain S; Wagener MM; Singh N
INSTITUCIÓN
/ INSTITUTION: - Veterans Affairs Medical Center and University
of Pittsburgh, Thomas E. Starzl Transplantation Institute, Pittsburgh,
Pennsylvania 15240, USA.
RESUMEN
/ SUMMARY: - Unique clinical characteristics and other
variables influencing the outcome of Cryptococcus neoformans infection in organ
transplant recipients have not been well defined. From a review of published
reports, we found that C. neoformans infection was documented in 2.8% of organ
transplant recipients (overall death rate 42%). The type of primary
immunosuppressive agent used in transplantation influenced the predominant
clinical manifestation of cryptococcosis. Patients receiving tacrolimus were
significantly less likely to have central nervous system involvement (78%
versus 11%, p =0.001) and more likely to have skin, soft-tissue, and osteoarticular
involvement (66% versus 21%, p = 0.006) than patients receiving nontacrolimus-
based immunosuppression. Renal failure at admission was the only independently
significant predictor of death in these patients (odds ratio 16.4, 95% CI
1.9-143, p = 0.004). Hypotheses based on these data may elucidate the
pathogenesis and may ultimately guide the management of C. neoformans infection
in organ transplant recipients. N.
Ref:: 74
----------------------------------------------------
[18]
TÍTULO / TITLE: - Mechanisms and
consequences of arterial hypertension after renal transplantation.
REVISTA
/ JOURNAL: - Transplantation 2001 Sep 27;72(6
Suppl):S9-12.
AUTORES
/ AUTHORS: - Koomans HA; Ligtenberg G
INSTITUCIÓN
/ INSTITUTION: - Department of Nephrology and Hypertension,
University Hospital Utrecht, The Netherlands. h.a.koomans@digd.azu.nl
RESUMEN
/ SUMMARY: - The high incidence of hypertension after
renal transplantation contributes to the risk of cardiovascular morbidity and
mortality in renal transplant recipients. Although cyclosporine has been
influential in the improvement of transplant outcome, it has emerged as a major
cause of hypertension after organ transplantation. The underlying pathophysiological
mechanisms of cyclosporine-induced hypertension include enhanced sympathetic
nervous system activity, renal vasoconstriction, and sodium/water retention.
Hypertension is also significantly associated with reduced graft survival and
thereby requires aggressive treatment intervention. Calcium channel blockers
may offer some advantages over angiotensin-converting enzyme inhibitors for the
treatment of hypertension in stable renal transplant recipients. Nevertheless,
selection of the most appropriate antihypertensive agent should take into
account the possibility of pharmacokinetic interactions with immunosuppressive
agents. There is evidence to suggest that the use of tacrolimus-based
immunosuppression induces less hypertension compared with cyclosporine. Not
only do patients receiving tacrolimus tend to require less antihypertensive
therapy, but converting patients from cyclosporine to tacrolimus has been shown
to result in significant reductions in blood pressure. Thus, tacrolimus may be
associated with an improved cardiovascular risk profile in renal transplant
recipients. N. Ref:: 26
----------------------------------------------------
[19]
TÍTULO / TITLE: - Controlling the
incidence of infection and malignancy by modifying immunosuppression.
REVISTA
/ JOURNAL: - Transplantation 2001 Dec 27;72(12
Suppl):S89-93.
AUTORES
/ AUTHORS: - Soulillou JP; Giral M
RESUMEN
/ SUMMARY: - Long-term outcomes in renal
transplantation have improved over the years but are still a matter of concern.
Because patients typically require lifelong immunosuppression, the risks of
cancer and infection associated with immunosuppressive agents continue to
demand attention. Physicians strive endlessly to find the right balance between
the level of immunosuppression required to prevent rejection and the level that
will minimize dose-dependent side effects. Data presented in this paper suggest
that some renal transplant recipients might have more than necessary
immunosuppression during maintenance therapy and that reducing the immunosuppressant
dose can decrease cancer incidence, without worsening long-term patient or
allograft survival. Additionally, data were examined suggesting that
immunosuppressive agents might be associated with different risks for cancer,
specifically, the potential advantage of reduced cancer risk for sirolimus and
sirolimus derivatives in comparison with standard immunosuppressive agents.
Although promising, these preliminary results are from preclinical studies, and
further study is warranted. N.
Ref:: 42
----------------------------------------------------
[20]
TÍTULO / TITLE: - Effect of
immunosuppressive treatment protocol on malignancy development in renal
transplant patients.
REVISTA
/ JOURNAL: - Transplant Proc 2002 Sep;34(6):2133-5.
AUTORES
/ AUTHORS: - Haberal M; Moray G; Karakayali H; Emiroglu
R; Basaran O; Sevmis S; Demirhan B
INSTITUCIÓN
/ INSTITUTION: - Baskent University Faculty of Medicine,
Ankara, Turkey. melekk@baskent-ank.edu.tr
----------------------------------------------------
[21]
TÍTULO / TITLE: - Effective prophylactic
protocol in delayed hypersensitivity to contrast media: report of a case
involving lymphocyte transformation studies with different compounds.
REVISTA
/ JOURNAL: - Radiology. Acceso gratuito al texto
completo a partir de los 2 años de la publicación; - http://radiology.rsnajnls.org/
●●
Cita: Radiology: <> 2002 Nov;225(2):466-70.
AUTORES
/ AUTHORS: - Romano A; Artesani MC; Andriolo M; Viola
M; Pettinato R; Vecchioli-Scaldazza A
INSTITUCIÓN
/ INSTITUTION: - Department of Internal Medicine and
Geriatrics, Universita’ Cattolica del Sacro Cuore, Allergy Unit, Complesso
Integrato Columbus, Via G. Moscati 31, 00168 Rome, Italy. columbus.allerg@linet.it
RESUMEN
/ SUMMARY: - A patient with maculopapular reactions to
iopamidol needed to undergo angiography for a cerebral arteriovenous
malformation. In vivo and in vitro tests were performed with ionic and nonionic
contrast media, including iopamidol and iobitridol. All results were positive,
demonstrating delayed hypersensitivity. The patient received
6-alpha-methylprednisolone and cyclosporine 1 week before and 2 weeks after
four angiograms were obtained with the use of iobitridol, which was well
tolerated.
----------------------------------------------------
[22]
TÍTULO / TITLE: - Potential therapeutic
interventions to avoid or treat chronic allograft dysfunction.
REVISTA
/ JOURNAL: - Transplantation 2001 Jun 15;71(11
Suppl):SS52-7.
AUTORES
/ AUTHORS: - Kahan BD
INSTITUCIÓN
/ INSTITUTION: - University of Texas Medical School
Houston, United States.
RESUMEN
/ SUMMARY: - Despite the significant improvements that
have occurred since the introduction of CsA, long-term renal allograft survival
continues to be an area of concern. Management strategies that involve the use
of sirolimus offer some promise. A number of observations suggest that
sirolimus may have the ability to reduce the rates or slow the progression of
chronic nephropathy. First, sirolimus has been shown to inhibit
growth-factor-driven proliferation of endothelial and smooth muscle cells in
vitro (55, 56). Sirolimus also disrupts signal transduction by a variety of
other cytokines such as EGF and PDGE This is significant because cytokine- and
growth-factor-stimulated proliferation of endothelial cells, smooth muscle
cells, parenchymal cells, and fibroblasts appears to underlie the development
of chronic nephropathy (see Fellstrom, this supplement). Second, sirolimus has
been demonstrated in various animal models to inhibit the arterial intimal
thickening that typically follows alloimmune or mechanical injury (56-60; see
Morris, this supplement). This transplant vasculopathy is a prominent feature
in chronic rejection of other organ transplants. Moreover, at least 1 published
study has suggested that sirolimus may be able to stabilize and possibly
reverse chronic graft vascular disease (61). However, the relative doses of
sirolimus used in these animal studies have been higher than those used in
humans, so the relationship of these effects to the clinical setting needs to
be further studied to define the relevance of these findings. Third, sirolimus,
used in combination with CsA, reduces the incidence of acute rejection episodes
in humans, one of the most significant predictors of shortened renal allograft
survival (62, 63). Thus, an effect of sirolimus to reduce acute rejection
episodes or delay their onset is expected to reduce renal allograft loss.
Furthermore, clinical trials suggest that sirolimus treatment may allow dose
reductions of CsA or a delay in inception of CsA therapy, which might reduce
the acute and chronic nephrotoxicity associated with CsA and other CNIs. Since
nephrotoxicity may promote or aggravate renal injury and appears to be common
in chronic nephropathy (see Fellstrom and Paul, this supplement), reduced
exposure to CNIs may translate into reduced rates of chronic renal allograft
dysfunction. There are no currently effective therapies for chronic
nephropathy, which is a common cause of late renal allograft loss. Preliminary
evidence suggests that sirolimus may eventually prove useful as prophylaxis of
or treatment for chronic nephropathy. Thus, sirolimus has come to be regarded
as the foundation for maintenance immunosuppressive regimens. N. Ref:: 63
----------------------------------------------------
[23]
TÍTULO / TITLE: - Drug-eluting stents:
potential applications for peripheral arterial occlusive disease.
REVISTA
/ JOURNAL: - J Vasc Interv Radiol 2003
Mar;14(3):291-301.
AUTORES
/ AUTHORS: - Duda SH; Poerner TC; Wiesinger B; Rundback
JH; Tepe G; Wiskirchen J; Haase KK
INSTITUCIÓN
/ INSTITUTION: - Department of Diagnostic Radiology,
University of Tuebingen, Germany. stephan.duda@med.uni-tuebingen.de
RESUMEN
/ SUMMARY: - Many different approaches have been
evaluated to prevent restenosis in stents after vascular implantation.
Currently, drug-eluting stents are extremely promising in suppressing
neointimal hyperplasia. Various animal studies and randomized trials in humans
have shown excellent results in terms of safety and efficacy during
intermediate-term follow-up. This article will give an overview of experimental
and clinical data of the different agents in published and ongoing trials. N. Ref:: 87
----------------------------------------------------
[24]
TÍTULO / TITLE: - Engineered CD3
antibodies for immunosuppression.
REVISTA
/ JOURNAL: - Clin Exp Immunol 2003 Sep;133(3):307-9.
AUTORES
/ AUTHORS: - Renders L; Valerius T N. Ref:: 30
----------------------------------------------------
[25]
TÍTULO / TITLE: - Risk factors for
bronchiolitis obliterans: a systematic review of recent publications.
REVISTA
/ JOURNAL: - J Heart Lung Transplant 2002
Feb;21(2):271-81.
AUTORES
/ AUTHORS: - Sharples LD; McNeil K; Stewart S; Wallwork
J
INSTITUCIÓN
/ INSTITUTION: - Medical Research Council (MRC)
Biostatistics Unit, University Forvie Site, Papworth Everard, Cambridge, United
Kingdom. linda.sharples@mrc-bsu.cam.ac.uk
RESUMEN
/ SUMMARY: - BACKGROUND: Obliterative bronchiolitis
remains the major limitation to long-term survival after lung transplantation.
A thorough understanding of the factors that confer high risk of developing
obliterative bronchiolitis or its physiologic surrogate bronchiolitis obliterans
syndrome is important to help define therapeutic strategies. METHODS: We
performed a systematic review of studies published since the beginning of 1990.
The review excluded non-human studies, publications before 1990, small (less
than 25 patients) studies that were predominantly concerned with investigating
the pathogenesis of obliterative bronchiolitis, studies solely concerned with
diagnosis or treatment of obliterative bronchiolitis, and overlapping studies
from the same center. Onset of bronchiolitis obliterans syndrome or
obliterative bronchiolitis was the outcome of interest. RESULTS: Acute
rejection plays an important role in obliterative bronchiolitis and
bronchiolitis obliterans syndrome onset, and late rejection is a significant
risk factor. Lymphocytic bronchitis/bronchiolitis is also a risk factor, with
some evidence that late onset is associated with greater risk. The effects of
cytomegalovirus, other infectious organisms, and human leukocyte antigen
matching are less clear and require further confirmation. There is little
evidence that recipient and donor characteristics play a major role.
CONCLUSIONS: This systematic review supports the view that obliterative
bronchiolitis arises from alloimmunologic injury marked by clinically apparent acute
rejection episodes and that inflammatory conditions, including viral infections
or ischemic injury, may also play a role. Implications for therapy are
discussed. N. Ref:: 28
----------------------------------------------------
[26]
TÍTULO / TITLE: - Use of nonsteroidal
topical immunomodulators for the treatment of atopic dermatitis in the
pediatric population.
REVISTA
/ JOURNAL: - J Pediatr 2001 Feb;138(2):163-8.
AUTORES
/ AUTHORS: - Paller AS
INSTITUCIÓN
/ INSTITUTION: - Department of Pediatrics, Children’s
Memorial Hospital, Northwestern University Medical School, Chicago, Illinois,
USA. N. Ref:: 39
----------------------------------------------------
[27]
TÍTULO / TITLE: - The porcine coronary
model of in-stent restenosis: current status in the era of drug-eluting stents.
REVISTA
/ JOURNAL: - Catheter Cardiovasc Interv 2003
Dec;60(4):515-23.
●●
Enlace al texto completo (gratuito o de pago) 1002/ccd.10705