#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
AUTORES
/ AUTHORS: - Lowe HC; Schwartz RS; Mac Neill BD; Jang
IK; Hayase M; Rogers C; Oesterle SN
INSTITUCIÓN
/ INSTITUTION: - Cardiology Division, Massachusetts General
Hospital, Harvard Medical School, Boston, Massachusetts, USA. h.lowe@unsw.edu.au
RESUMEN
/ SUMMARY: - Drug-eluting stents are revolutionizing
interventional cardiology. Sirolimus-eluting stents are in widespread clinical
use, associated with well-documented remarkably low restenosis rates, and a
number of other agents appear promising in clinical trials. These human studies
have been preceded by numerous animal studies, foremost among them the pig
coronary model of in-stent restenosis (ISR). The histologic response to porcine
coronary stenting was described over a decade ago. Porcine stenting studies now
provide examinations not only of histology, but also mechanisms of action, toxicity,
and biocompatibility. This review therefore examines the current status of this
porcine coronary model of ISR. Contemporary methods of pig coronary stenting
are discussed. The morphometric, cellular, and molecular analyses of the
responses to stent injury are then described. Finally, recent pig coronary
drug-eluting stent studies are examined, with a discussion of their advantages,
limitations, and possible future modifications. N. Ref:: 51
----------------------------------------------------
[28]
TÍTULO / TITLE: - Drug-eluting stents in
peripheral vascular disease: eliminating restenosis.
REVISTA
/ JOURNAL: - Mt Sinai J Med. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.mssm.edu/msjournal/
●●
Cita: Mount Sinai J. of Medicine, New York: <> 2003 Nov;70(6):417-9.
AUTORES
/ AUTHORS: - Ellozy SH; Carroccio A
INSTITUCIÓN
/ INSTITUTION: - Department of Surgery, Mount Sinai School
of Medicine, One East 100th Street, New York, NY 10029, USA. sharif.ellozy@msnyuhealth.org
RESUMEN
/ SUMMARY: - Transcatheter endovascular therapy for
peripheral atherosclerotic disease has become more popular. In general, good
results have been reported in focal aortoiliac disease. However, the long-term
patency of angioplasty in longer, more distal lesions has been less
satisfactory. Stenting has not been shown to improve long-term patency compared
to angioplasty alone. Drug-eluting stents have shown promise in preventing
coronary restenosis, and preliminary results in peripheral arterial disease are
encouraging. This review article will discuss the current status of
endovascular therapy of aortoiliac and femoropopliteal atherosclerotic disease,
the theoretic and experimental basis for the use of drug-eluting stents, and
the preliminary results in human studies.
N. Ref:: 48
----------------------------------------------------
[29]
TÍTULO / TITLE: - Rejection rate in
living donor kidney transplantation with and without basiliximab in
tacrolimus/mycophenolate mofetil-based protocol.
REVISTA
/ JOURNAL: - Transplant Proc 2003 Mar;35(2):653-4.
AUTORES
/ AUTHORS: - Rahamimov R; Yussim A; After T; Lustig S;
Bar-Nathan N; Shaharabani E; Shapira Z; Shabthai E; Mor E
INSTITUCIÓN
/ INSTITUTION: - Department of Transplantation, Rabin
Medical Center, Beilinson Campus, Petah-Tiqwa, Israel. rutir@clalit.org.il
----------------------------------------------------
[30]
- Castellano -
TÍTULO / TITLE:Presentacion de canceres en
receptores trasplantados con organo solido. Presentation of cancers in
recipients of a solid-organ transplant.
REVISTA
/ JOURNAL: - Nefrologia. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.aulamedica.es/nefrologia/
●●
Cita: Nefrologia: <> 2001;21(6):528-37.
AUTORES
/ AUTHORS: - Lampreabe I; Gomez-Ullate P; Amenabar JJ;
Zarraga S; Gainza FJ; Urbizu JM
INSTITUCIÓN
/ INSTITUTION: - Servicio de Nefrologia, Hospital de
Cruces, Facultad de Medicina, Universidad del Pais Vasco. ilampreave@hcru.osakidetza.net N. Ref:: 35
----------------------------------------------------
[31]
TÍTULO / TITLE: - Limited dose monoclonal
IL-2R antibody induction protocol after primary kidney transplantation.
REVISTA
/ JOURNAL: - Am J Transplant 2002 Jul;2(6):568-73.
AUTORES
/ AUTHORS: - Ahsan N; Holman MJ; Jarowenko MV; Razzaque
MS; Yang HC
INSTITUCIÓN
/ INSTITUTION: - Nephrology and Transplant Division,
University of Medicine and Dentistry of New Jersey, New Brunswick 08904, USA. ahsanna@umdnj.edu
RESUMEN
/ SUMMARY: - This study prospectively compared
immunoprophylaxis with a single intraoperative dose (2 mg/kg) of monoclonal
interleukin-2 receptor (IL-2R) antibody vs. noninduction in kidney transplant
recipients treated with tacrolimus (FK 506), mycophenolate mofetil (MMF) and a
prednisone-based immunosuppression regimen. One hundred recipients of
first-kidney transplant were enrolled into the study to receive either
anti-IL-2R monoclonal antibody, daclizumab (2 mg/kg intraoperatively, limited
anti-IL-2R) or no induction (control). Each patient also received oral
tacrolimus (dosed to target trough level 10-15 ng/mL), MMF (500 mg bid) and
prednisone. The primary efficacy end-point was the incidence of biopsy proven
acute rejection during the first 6 months post-transplant. The patients were
also followed for 12-month graft function, and graft and patient survival
rates. Other than the donor’s age being significantly lower in the control
group, both groups were comparable with respect to age, weight, gender, race, human
leukocyte antigen (HLA)-DR mismatch, panel reactive antibody (%PRA), cold
ischemic time, cytomegalovirus (CMV) status, causes of renal failure, and
duration and modes of renal replacement therapy (RRT). During the first 6
months, episodes of first biopsy confirmed acute rejection was 3/50 (6%) in the
limited anti-IL-2R group and 8/50 (16%) in the controls (p < 0.05).
Twelve-month patient 100/98 (%) and graft survival 100/96 (%) were not
statistically different. The group receiving limited anti-IL-2R did not have
any adverse reactions. Our study demonstrates that a limited (single) 2 mg/kg
immunoprophylaxis dose with monoclonal IL-2R antibody (daclizumab) when
combined with tacrolimus/MMF/steroid allows significant reduction in early
renal allograft rejection to the single digit level. The therapy with
anti-IL-2R antibody is simple and is well tolerated.
----------------------------------------------------
[32]
TÍTULO / TITLE: - Antioxidant nutrients
protect against cyclosporine A nephrotoxicity.
REVISTA
/ JOURNAL: - Toxicology 2003 Jul 15;189(1-2):99-111.
AUTORES
/ AUTHORS: - Parra Cid T; Conejo Garcia JR; Carballo
Alvarez F; de Arriba G
INSTITUCIÓN
/ INSTITUTION: - Unidad de Investigacion, Hospital
Universitario de Guadalajara, C/Donante de Sangre s/n, 19.002 Guadalajara,
España. tparracid@hotmail.com
RESUMEN
/ SUMMARY: - The immunosuppressive drug cyclosporine A
(CsA) has been successfully used in several diseases with immunological basis
and in transplant patients. Nephrotoxicity is the main secondary effect of CsA
treatment. Although the mechanisms of nephrotoxitity are not completely
defined, there is evidence that suggests the role of reactive oxygen species
(ROS) in its pathogenesis. It has been demonstrated in numerous in vivo and in
vitro experiments that CsA induced renal failure and increased the synthesis of
ROS, thromboxane (TX) and lipid peroxidation products in the kidney.
Furthermore, CsA modified the expression and activity of several renal enzymes
(ciclooxygenase, superoxide-dismutase, catalase and glutathione-peroxidase).
Antioxidant nutrients (e.g. Vitamins E and C) can neutralize some of the
effects that CsA produced in the kidney. Thus, Vit E inhibited the synthesis of
ROS and TX and the lipid peroxidation process induced by CsA in kidney
structures. Antioxidants can also improve renal function and histological
damage produced by CsA administration. Although there are few data in humans
treated with CsA, the possibility exists that antioxidants can also neutralize
CsA nephrotoxicity and LDL oxidation. Thus, antioxidant nutrients could have a
therapeutic role in transplant patients treated with CsA. N. Ref:: 79
----------------------------------------------------
[33]
TÍTULO / TITLE: - Role of prostanoids and
endothelins in the prevention of cyclosporine-induced nephrotoxicity.
REVISTA
/ JOURNAL: - Prostaglandins Leukot Essent Fatty Acids
2001 Apr-May;64(4-5):231-9.
●●
Enlace al texto completo (gratuito o de pago) 1054/plef.2001.0265
AUTORES
/ AUTHORS: - Darlametsos IE; Varonos DD
INSTITUCIÓN
/ INSTITUTION: - Centre Franco-Hellenique de Recherches
Biomedicales, Nikolaos Papanikolaou, Corporation of the Municipality Agrinion,
Agrinion, 30100, Greece. darlamet@otenet.gr
RESUMEN
/ SUMMARY: - Cyclosporine A nephrotoxicity includes
both functional toxicity and histological changes, whose seriousness is
dependent upon the dose and the duration of the drug administration. Several
vasoactive agents have been found to be implicated in cyclosporine induced
nephrotoxicity, among which prostanoids and endothelins are the most important.
In previous studies we were able to prevent the early stage (7 days) of
cyclosporine (37.4 micromol [45 mg]/kg/day) induced nephrotoxicity in rats
either by the administration, i) of OKY-046, a thromboxane A(2)synthase
inhibitor, ii) of ketanserine, an antagonist of S(2)serotonergic,
a(1)adrenergic, and H(1)histaminergic receptors and iii) of nifedipine, a
calcium channel blocker, or by diet supplementation either with evening
primrose oil or fish oil. All these protective agents elevated ratios of
excreted renal prostanoid vasodilators (prostaglandins E(2), 6ketoF(1 alpha))
to vasoconstrictor (thromboxane B(2)), a ratio which was decreased by the
administration of cyclosporine alone. Nifedipine averted the cyclosporine
induced increase of urinary endothelin-1 release. All protections were
associated with the reinstatement of glomerular filtration rate forwards normal
levels whereas renal damage defence, consisting of a decrease of the
cyclosporine induced vacuolizations, was variable. Ketanserine and evening
primrose oil were the only agents which prevented the animal body weight loss.
These data suggest that prostanoids and endothelin-1 may mediate functional
toxicity while thromboxane A(2)is involved the morphological changes too,
provoked in the early stage of cyclosporine treatment. However, other
nephrotoxic factors and additional mechanisms could also be implicated in the
cyclosporine induced nephrotoxicity. N.
Ref:: 91
----------------------------------------------------
[34]
TÍTULO / TITLE: - New strategies to
reduce nephrotoxicity.
REVISTA
/ JOURNAL: - Transplantation 2001 Dec 27;72(12
Suppl):S99-104.
AUTORES
/ AUTHORS: - Kreis H
RESUMEN
/ SUMMARY: - Since the introduction of cyclosporine,
CNIs have formed the basis of immunosuppressive therapy in renal
transplantation. The propensity of these agents to ultimately damage the very
organs they were intended to protect was always recognized, but largely ignored
due to their impressive ability to improve short-term outcomes. With the
availability of equally powerful new immunosuppressive agents devoid of major nephrotoxicity,
the irony of this situation has become all too apparent, and investigators are
beginning to reevaluate the role of CNIs in renal transplantation. In this
paper, we looked at strategies using MMF or sirolimus to reduce, withdraw, or
replace CNIs in renal transplantation. Although MMF has proved effective in
combination with CNIs, particularly in reducing acute rejection rates, its use
as base therapy to allow CNI therapy to be withdrawn or eliminated is
questionable. On the basis of initial trials, sirolimus holds promise for use
as base therapy. To date, it is probably the only agent used in renal
transplantation that provides immunosuppression comparable to cyclosporine or
tacrolimus, which may someday allow sirolimus to replace. CNIs or allow early
withdrawal of CNI therapy. Further study is needed to better clarify the role
of sirolimus in improving long-term renal transplantation outcomes. N. Ref:: 61
----------------------------------------------------
[35]
TÍTULO / TITLE: - Molecular actions of
sirolimus: sirolimus and mTor.
REVISTA
/ JOURNAL: - Transplant Proc 2003 May;35(3
Suppl):227S-230S.
AUTORES
/ AUTHORS: - Kirken RA; Wang YL
INSTITUCIÓN
/ INSTITUTION: - Department of Integrative Biology and
Pharmacology, The University of Texas Health Science Center at Houston,
Houston, Texas 77030, USA. robert.a.kirken@uth.tmc.edu
RESUMEN
/ SUMMARY: - Recent therapeutic strategies to combat
organ allograft rejection have focused on T-cell signaling pathways and the
molecules that comprise them. The macrolide antibiotic produced by the
bacterium Streptomyces hygroscopicus, known as sirolimus or rapamycin, has
shown great therapeutic potential in the transplant setting. Sirolimus alone or
in combination with other immunosuppressive agents can block acute rejection,
chronic graft destruction, and promote permanent allograft acceptance.
Sirolimus targets a unique serine-threonine kinase, mammalian target of
rapamycin (mTor), which plays a key role in mitogenic and nutritional cells
signals. Within T cells, mTor regulates a number of proteins likely dependent
on T cell growth factors such as interleukin 2. This review is focused on the
molecular mechanisms by which mTor may regulate T-cell signaling cascades and
affect T-cell responsiveness, and how sirolimus likely uncouples this
activity. N. Ref:: 32
----------------------------------------------------
[36]
TÍTULO / TITLE: - Long-term kidney
transplant survival.
REVISTA
/ JOURNAL: - Am J Kidney Dis 2001 Dec;38(6 Suppl
6):S44-50.
AUTORES
/ AUTHORS: - Hariharan S
INSTITUCIÓN
/ INSTITUTION: - Froedert Memorial Hospital, Medical
College of Wisconsin, Milwaukee, WI 53226, USA. hari@mcw.edu
RESUMEN
/ SUMMARY: - With improvements in short-term kidney
graft survival, focus has shifted towards long-term survival. There has also
been a substantial improvement in long-term survival as measured by kidney
half-life. Long-term graft failure is secondary to chronic allograft
nephropathy (CAN), recurrent disease, and death with a functioning graft. CAN
is secondary to a combination of chronic rejection, chronic cyclosporine
toxicity, and/or donor kidney disease. Risk factors for chronic rejection have
been attributed to both immunological and nonimmunological causes. With a
marked reduction in acute rejection rates-an important risk factor for
CAN-there is a substantial improvement in kidney half-life. There are still
nonimmunological factors, such as donor age, that adversely affect long-term
graft survival. In addition, African-American recipients continue to have a
shorter graft half-life. Recurrent disease is becoming an important cause of
late graft failure. Despite the introduction of various potent
immunosuppressive agents, there has been little or no impact on the prevalence
as well as progression of recurrent diasease. With the reduction of acute
rejection rates and improved short- and long-term graft survival, further
improvements of long-term graft survival will be an important focus in the 21st
century. N. Ref:: 45
----------------------------------------------------
[37]
TÍTULO / TITLE: - Prevention strategies
for type 1 diabetes mellitus: current status and future directions.
REVISTA
/ JOURNAL: - BioDrugs 2003;17(1):39-64.
AUTORES
/ AUTHORS: - Winter WE; Schatz D
INSTITUCIÓN
/ INSTITUTION: - Department of Pathology, University of
Florida, Gainesville, Florida 32610, USA. winter@pathology.ufl.edu
RESUMEN
/ SUMMARY: - Type 1 diabetes mellitus affects about 1
in 300 people in North America and Europe. Epidemiological studies indicate
that the incidence and thus prevalence of type 1 diabetes is rising worldwide.
Intervention in autoimmune type 1a diabetes could occur at the time of
diagnosis or, preferably, prior to clinical presentation during the
‘prediabetic’ period (e.g. prevention). Prediabetes is best recognised by the
detection of islet autoantibodies in the serum. Promising intervention
strategies include monoclonal antibody therapies (e.g. anti-CD3, anti-CD25,
anti-CD52 or anti-CD20 monoclonal antibodies), immunosuppression (e.g.
calcineurin inhibitors, B7 blockade, glucocorticoids, sirolimus (rapamycin),
azathioprine or mycophenolate mofetil), immunomodulatory therapies (e.g.
plasmapheresis, intravenous immunoglobulin, cytokine administration, adoptive
cellular gene therapy) and tolerisation interventions (e.g. autoantigen
administration or avoidance, altered peptide ligand or peptide-based
therapies). To date, islet and pancreas transplantation have essentially been
reserved for patients with long-standing diabetes who have complications and
are also in need of a concurrent kidney transplant. None of the therapies
attempted to date has produced long-term remissions in new-onset type 1
diabetes patients and no therapies have been shown to prevent the disease.
Nevertheless, with advances in our understanding of basic immunology and the
cellular and molecular mechanisms of tolerance induction and maintenance, successful
intervention therapies will be developed. The balance between safety and
efficacy is critical. Higher rates of adverse events might be more tolerable in
new-onset type 1 diabetes patients if the therapy is extremely effective at
inducing a permanent remission. However, therapies must not harm the beta-cells
themselves or any organ system that is a potential target of diabetes
complications, such as the nervous system, retina, cardiovascular system or
kidney. In the treatment of prediabetes, successful therapies should provide a
level of safety similar to that of currently used vaccines and a high level of
efficacy. N. Ref:: 244
----------------------------------------------------
[38]
TÍTULO / TITLE: - Tailoring
immunosuppressive therapy based on donor and recipient risk factors.
REVISTA
/ JOURNAL: - Transplant Proc 2001 May;33(3):2207-11.
AUTORES
/ AUTHORS: - First MR
INSTITUCIÓN
/ INSTITUTION: - University of Cincinnati Medical Center,
Cincinnati, Ohio 45267-0585, USA. N.
Ref:: 35
----------------------------------------------------
[39]
TÍTULO / TITLE: - Novel
pharmacotherapeutic approaches to prevention and treatment of GVHD.
REVISTA
/ JOURNAL: - Drugs 2002;62(6):879-89.
AUTORES
/ AUTHORS: - Jacobsohn DA; Vogelsang GB
INSTITUCIÓN
/ INSTITUTION: - Oncology and Pediatrics, The Johns Hopkins
University School of Medicine, Baltimore, Maryland, USA. jacobda@jhmi.edu
RESUMEN
/ SUMMARY: - Acute and chronic graft versus host
disease (GVHD) remain the major barriers to successful hematopoietic cell
transplantation. The induction of GVHD may be divided into three phases:
recipient conditioning;donor T-cell activation; andeffector cells mediating
GVHD. This review examines GVHD prevention and treatment using this conceptual
model as framework. The various pharmacological agents discussed impact on
different phases of the GVHD cascade. For example, keratinocyte growth factor
and interleukin (IL)-11 are cytokines that may be useful in disrupting phase I
of the GVHD cascade by blocking gastrointestinal tract damage, and lowering
serum levels of lipopolysaccharide and tumour necrosis factor (TNF)-alpha.
Cyclosporin, tacrolimus (FK-506) and sirolimus (rapamycin) are some of the main
agents that disrupt phase II (donor T-cell activation). Mycophenolate mofetil
and tresperimus probably act on this phase as well. Other novel drugs that
affect phase II are tolerance-induction agents such as CTLA-4 and
anti-CD40-ligand monoclonal antibodies, and preliminary results using CTLA-4
monoclonal antibody in GVHD prevention are encouraging. Examples of agents that
disrupt phase III are the IL-2 receptor antagonist daclizumab and the
anti-TNFalpha monoclonal antibody infliximab. These anti-cytokine antibodies
have shown promising results in early studies. The most effective approach to
GVHD prevention will probably be a combination regimen where the three phases
of the GVHD cascade are disrupted. Once GVHD has occurred, all three phases of
the cascade are activated. Developments of combination therapy for treatment of
both acute and chronic GVHD are likely to yield better results than
monotherapy. The numerous new treatment modalities presented should improve the
outlook for patients with acute and chronic GVHD. N. Ref:: 74
----------------------------------------------------
[40]
TÍTULO / TITLE: - Incidence and spectrum
of infections in lung transplanted patients: comparison of four different
immunosuppressive protocols.
REVISTA
/ JOURNAL: - Transplant Proc 2001 Feb-Mar;33(1-2):1620-1.
AUTORES
/ AUTHORS: - Treede H; Reichenspurner H; Meiser BM; Kur
F; Furst H; Vogelmeier C; Briegel J; Reichart B
INSTITUCIÓN
/ INSTITUTION: - University Hospital Grosshadern, Munich,
Germany.
----------------------------------------------------
[41]
TÍTULO / TITLE: - Early clinical
experience with a novel rapamycin derivative.
REVISTA
/ JOURNAL: - Ther Drug Monit 2002 Feb;24(1):53-8.
AUTORES
/ AUTHORS: - Nashan B
INSTITUCIÓN
/ INSTITUTION: - Klinik fur Viszeral-und
Transplantationschirurgie, Medizinische Hochschule Hannover, Hannover, Germany.
nashan@tx-amb.mh-hannover.de
RESUMEN
/ SUMMARY: - SDZ RAD (everolimus, Certican is a novel
macrolide immunosuppressant that blocks growth factor-driven transduction
signals in the T-cell response to alloantigen. After stimulation of the IL-2
receptor on the activated T-cell, SDZ RAD inhibits p70S6 kinase, acting at a
later stage in the T-cell mediated response than do cyclosporine and other
calcineurin inhibitors (CNIs). Unlike the CNIs, SDZ RAD is a proliferation
signal inhibitor, blocking growth factor-driven proliferation of both
hematopoietic and nonhematopoietic cells. These activities are complementary to
those of cyclosporine and provide a rationale for the addition of SDZ RAD to
cyclosporine-based immunosuppression, with the potential for minimizing CNI
nephrotoxicity, reducing the incidence of acute rejection, and favoring
long-term graft survival. Potential also exists for beneficial effects on other
factors that may influence the development of chronic rejection. These factors
include comorbid diseases such as hypertension, which may affect transplant
vasculopathy, and opportunistic infection with cytomegalovirus (CMV) and other
viruses, which may increase the risk of chronic rejection. The synergistic
effect of SDZ RAD and cyclosporine has been confirmed in preclinical models,
with graft survival being significantly prolonged in rat models of kidney and
heart allotransplantation. Clinical experience with SDZ RAD in
cyclosporine-based immunosuppression, including low-dose cyclosporine regimens,
has also resulted in predictable and favorable clinical outcomes. Low rates of
acute rejection, excellent rates of patient and graft survival, lower incidence
of CMV infections, better cholesterol, triglyceride and creatinine profiles,
and better renal function have been demonstrated with SDZ RAD and lower doses
of cyclosporine (Neoral; Novartis) in recipients of renal transplants. These
findings, combined with good tolerability rates and an acceptable side-effect
profile, indicate that the synergistic profile of SDZ RAD in combination with
nontoxic dosages of CNI’s and IL2 inhibitors will further improve longterm
results in renal transplantation. N.
Ref:: 48
----------------------------------------------------
[42]
TÍTULO / TITLE: - The role of newer
monoclonal antibodies in renal transplantation.
REVISTA
/ JOURNAL: - Transplant Proc 2001
Feb-Mar;33(1-2):1000-1.
AUTORES
/ AUTHORS: - Vincenti F
INSTITUCIÓN
/ INSTITUTION: - University of California, San Francisco,
California, USA. N.
Ref:: 5
----------------------------------------------------
[43]
TÍTULO / TITLE: - Daclizumab: a review of
its use in the management of organ transplantation.
REVISTA
/ JOURNAL: - BioDrugs 2001;15(11):745-73.
AUTORES
/ AUTHORS: - Carswell CI; Plosker GL; Wagstaff AJ
INSTITUCIÓN
/ INSTITUTION: - Adis International Limited, Auckland, New
Zealand. demail@adis.co.nz
RESUMEN
/ SUMMARY: - The humanised monoclonal antibody
daclizumab is an immunosuppressive agent that reduces acute rejection in solid
organ transplantation. It is specific for the alpha subunit (Tac/CD25) of the
interleukin (IL)-2 receptor on activated T cells and achieves immunosuppression
by competitive antagonism of IL-2-induced T cell proliferation. When added to
standard triple immunosuppression regimens, daclizumab significantly reduces
the rate of acute rejection at 1 year in renal transplantation by 36% and there
are indications that it may be effective in other solid organ transplantations.
Three-year outcomes of two phase III clinical trials in renal transplantation
indicate similar values for graft and patient survival between daclizumab and
placebo when given in addition to triple immunosuppression; however, these
pivotal trials were not designed with sufficient power to demonstrate any
statistical significance. The addition of daclizumab induction shows potential
in allowing calcineurin inhibitor- and corticosteroid-sparing regimens without
increasing the rate of acute graft rejection or adverse effects in renal and
liver transplantation. Preliminary reports indicate that daclizumab may also be
a useful agent in delayed graft function and graft versus host disease (GVHD).
Further investigation of its efficacy in these groups and in children is
needed. Data from clinical trials show daclizumab to be well tolerated in solid
organ transplantation. It does not increase the incidence of infection,
including cytomegalovirus infection, when compared with placebo or no induction
groups. Preliminary comparative data with muromonab CD3 indicate that
daclizumab may be associated with a lower rate of infectious complications and
similar or better efficacy. CONCLUSIONS: In conclusion, daclizumab has been
proven to reduce acute rejection in renal transplant recipients when given in
addition to traditional baseline immunosuppression. It has shown potential to
reduce acute rejection in other solid organ transplants; however, well designed,
randomised studies are required to confirm this. Clinical experience from
trials to date indicate that daclizumab has a tolerability profile similar to
placebo with no significant effect on the incidence of infection. The relative
efficacy and tolerability of daclizumab compared with other induction agents
has yet to be defined. Available data suggest that daclizumab may allow the use
of calcineurin inhibitor-sparing and corticosteroid-sparing regimens and may
have potential in the treatment of GVHD.
N. Ref:: 80
----------------------------------------------------
[44]
TÍTULO / TITLE: - In-stent stenosis:
pathology and implications for the development of drug eluting stents.
REVISTA
/ JOURNAL: - Heart 2003 Feb;89(2):218-24.
AUTORES
/ AUTHORS: - Bennett MR
INSTITUCIÓN
/ INSTITUTION: - Addenbrooke’s Centre for Clinical
Investigation, Box 110, Addenbrooke’s Hospital, Cambridge CB2 2QQ, UK. mrb@mole.bio.cam.ac.uk N. Ref:: 20
----------------------------------------------------
[45]
TÍTULO / TITLE: - Strategies to reduce
toxicities and improve outcomes in renal transplant recipients.
REVISTA
/ JOURNAL: - Pharmacotherapy 2002 Mar;22(3):316-28.
AUTORES
/ AUTHORS: - Lo A; Alloway RR
INSTITUCIÓN
/ INSTITUTION: - Department of Surgery, University of
Cincinnati Medical Center, Ohio 45267-0585, USA.
RESUMEN
/ SUMMARY: - Ongoing improvements in immunosuppression
and posttransplantation care have dramatically improved patient and graft
outcomes after transplantation. The frequency of graft loss due to acute
rejection has declined considerably as a result of the availability of a
variety of more potent immunosuppressive agents and probably also because of
refined clinical care and follow-up. Complications of long-term administration
of corticosteroids (steroids) and calcineurin inhibitors, however, have become
increasingly apparent as patients live longer with their transplant, and
attention is shifting to long-term issues. Use of both steroids and calcineurin
inhibitors is associated with metabolic toxicities such as hypertension,
hyperlipidemia, diabetes, bone loss, and cataracts. These contribute to
posttransplantation morbidity and may negatively affect patient and allograft
survival. A variety of troublesome cosmetic side effects, such as hirsutism,
gingival hyperplasia, alopecia, obesity, and cushingoid appearance, also are
associated with these drugs. These effects can detract from patient self-esteem
and compliance with the immunosuppressive regimen. In the past 2 decades, the
introduction of second-generation immunosuppressive drugs, such as tacrolimus,
mycophenolate mofetil, sirolimus, and anti-interleukin-2 receptor monoclonal
antibodies, has provided some alternatives to classic immunosuppressant choices.
Patients experiencing undesirable adverse events now can be converted to
another immunosuppressive regimen that ultimately will improve graft and
patient survival rates and improve quality of life after transplantation. N. Ref:: 99
----------------------------------------------------
[46]
TÍTULO / TITLE: - Tacrolimus: a further
update of its use in the management of organ transplantation.
REVISTA
/ JOURNAL: - Drugs 2003;63(12):1247-97.
AUTORES
/ AUTHORS: - Scott LJ; McKeage K; Keam SJ; Plosker GL
INSTITUCIÓN
/ INSTITUTION: - Adis International Limited, Auckland, New
Zealand. demail@adis.co.nz
RESUMEN
/ SUMMARY: - Extensive clinical use has confirmed that
tacrolimus (Prograf) is a key option for immunosuppression after
transplantation. In large, prospective, randomised, multicentre trials in
adults and children receiving solid organ transplants, tacrolimus was at least
as effective or provided better efficacy than cyclosporin microemulsion in
terms of patient and graft survival, treatment failure rates and the incidence
of biopsy-proven acute and corticosteroid-resistant rejection episodes.
Notably, the lower incidence of rejection episodes after renal transplantation
in tacrolimus recipients was reflected in improved cost effectiveness. In bone
marrow transplant (BMT) recipients, the incidence of tacrolimus grade II-IV
graft-versus-host disease was significantly lower with tacrolimus than
cyclosporin treatment. Efficacy was maintained in renal and liver transplant
recipients after total withdrawal of corticosteroid therapy from
tacrolimus-based immunosuppression, with the incidence of acute rejection
episodes at up to 2 years’ follow-up being similar with or without
corticosteroids. Tacrolimus provided effective rescue therapy in transplant
recipients with persistent acute or chronic allograft rejection or drug-related
toxicity associated with cyclosporin treatment. Typically, conversion to
tacrolimus reversed rejection episodes and/or improved the tolerability
profile, particularly in terms of reduced hyperlipidaemia. In lung transplant
recipients with obliterative bronchiolitis, conversion to tacrolimus reduced
the decline in and/or improved lung function in terms of forced expiratory
volume in 1 second. Tolerability issues may be a factor when choosing a
calcineurin inhibitor. Cyclosporin tends to be associated with a higher
incidence of significant hypertension, hyperlipidaemia, hirsutism, gingivitis
and gum hyperplasia, whereas the incidence of some types of neurotoxicity,
disturbances in glucose metabolism, diarrhoea, pruritus and alopecia may be
higher with tacrolimus treatment. Renal function, as assessed by serum
creatinine levels and glomerular filtration rates, was better in tacrolimus
than cyclosporin recipients at up to 5 years’ follow-up. CONCLUSION: Recent
well designed trials have consolidated the place of tacrolimus as an important
choice for primary immunosuppression in solid organ transplantation and in BMT.
Notably, in adults and children receiving transplants, tacrolimus-based primary
immunosuppression was at least as effective or provided better efficacy than
cyclosporin microemulsion treatment in terms of patient and graft survival,
treatment failure and the incidence of acute and corticosteroid-resistant
rejection episodes. The reduced incidence of rejection episodes in renal
transplant recipients receiving tacrolimus translated into a better cost
effectiveness relative to cyclosporin microemulsion treatment. The optimal
immunosuppression regimen is ultimately dependent on balancing such factors as
the efficacy of the individual drugs, their tolerability, potential for drug
interactions and pharmacoeconomic issues.
N. Ref:: 261
----------------------------------------------------
[47]
TÍTULO / TITLE: - Post-liver transplant
obesity and diabetes.
REVISTA
/ JOURNAL: - Curr Opin Clin Nutr Metab Care 2003
Jul;6(4):457-60.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.mco.0000078994.96795.d8
AUTORES
/ AUTHORS: - T D
Correia MI; Rego LO; Lima AS
INSTITUCIÓN
/ INSTITUTION: - Alfa Institute of Gastroenterology,
University Hospital, Federal University of Minas Gerais, Brazil. Isabel_correia@uol.com.br
RESUMEN
/ SUMMARY: - PURPOSE OF REVIEW: Post-liver transplant
patients present a vast array of metabolic changes in the early and late phase
which impact on their morbidity and mortality. The development of obesity and
diabetes in these patients has been widely described in the literature with
several hypotheses suggested: liver donor, nutritional and metabolic state, and
immunosuppressive drugs. RECENT FINDINGS: Most that is known about the
development of these metabolic derangements has been attributed to the drugs
used, especially the corticosteroids. When these have been used in higher doses
for longer periods to treat rejection, the incidence of diabetes and obesity
seems to be higher. However cyclosporine and to a lesser extent tacrolimus are
also related to these alterations. SUMMARY: As long-term survival improves in
liver transplant patients, cardiovascular complications associated with
dyslipidemia, obesity, and diabetes are emerging as risk factors for late
morbidity and mortality. Therefore, it is important to assess the potential
risk factors related to these complications, in order to prevent or decrease
their incidence. From what has been seen, immunossupressive drugs seem to be
the greatest risk factor for the development of metabolic derangements in
post-transplantation patients. However other risk factors might also be
involved, such as non-healthy eating habits and lack of exercise. The latter
can be preventable if counseling policies are targeted at these patients in the
pre-transplantation phase and continued after the operation. N. Ref:: 27
----------------------------------------------------
[48]
TÍTULO / TITLE: - Sirolimus-based
immunosuppressive [correction of immunosuppresive] protocol for calcineurin
sparing in liver transplantation.
REVISTA
/ JOURNAL: - Transplant Proc 2002 Aug;34(5):1522-3.
AUTORES
/ AUTHORS: - Heffron TG; Smallwood GA; Davis L;
Martinez E; Stieber AC
INSTITUCIÓN
/ INSTITUTION: - Department of Surgery, Emory University
School of Medicine, Atlanta, GA 30322, USA.
----------------------------------------------------
[49]
TÍTULO / TITLE: - Immunosuppressive drug
use in pregnancy.
REVISTA
/ JOURNAL: - Autoimmunity 2003 Feb;36(1):51-6.
AUTORES
/ AUTHORS: - Petri M
INSTITUCIÓN
/ INSTITUTION: - Johns Hopkins University School of
Medicine, 1830 E. Monument Street, Suite 7500, Baltimore, MD 21205, USA.
RESUMEN
/ SUMMARY: - Ideally, immunosuppressive drugs would not
be necessary in pregnancy. However, in connective tissue disease (especially
systemic lupus erythematosus, SLE) vasculitis, and sometimes antiphospholipid
antibody syndrome, their use is necessary both to protect the health of the
mother and to insure the success of the pregnancy. The more commonly used drugs
will be reviewed, with an emphasis on human data, when available. Methotrexate
and leflunamide will not be considered, for they should never be used in
pregnancy. N. Ref:: 105
----------------------------------------------------
[50]
TÍTULO / TITLE: - Immunosuppression
protocols for HLA identical renal transplant recipients.
REVISTA
/ JOURNAL: - Transplant Proc 2003 May;35(3):1074-5.
AUTORES
/ AUTHORS: - Keitel E; Santos AF; Alves MA; Neto JP;
Schaefer PG; Bittar AE; Goldani JC; Pozza R; Bruno RM; See D; Garcia CD; Garcia
VD
INSTITUCIÓN
/ INSTITUTION: - Renal Transplant Unit, Santa Casa
Hospital, Porto Alegre, RS, Brazil. keitel@terra.com.br
----------------------------------------------------
[51]
TÍTULO / TITLE: - Squamous cell carcinoma
of the head and neck in solid organ transplant recipients.
REVISTA
/ JOURNAL: - Head Neck 2002 Apr;24(4):319-25.
●●
Enlace al texto completo (gratuito o de pago) 1002/hed.10055 [pii]
AUTORES
/ AUTHORS: - Preciado DA; Matas A; Adams GL
INSTITUCIÓN
/ INSTITUTION: - Department of Otolaryngology-Head and Neck
Surgery, University of Minnesota, Fairview University Medical Center, MMC 396,
420 Delaware Street SE, Minneapolis, MN 55455, USA. preci001@tc.umn.edu
RESUMEN
/ SUMMARY: - BACKGROUND: The increased incidence of
cancer after solid organ transplantation is well established in the literature,
yet outcome studies in this population are rare. Excluding skin cancers,
squamous cell carcinomas make up most head and neck cancers in transplant
recipients. METHODS: At our institution, of 5300 solid organ transplant
recipients, 34 have had head and neck cancer develop. We reviewed the records
of the 23 recipients whose cancer was treated here. RESULTS: Only 6 of the 23
recipients were alive at the time of our chart review. Of these, three had
already survived 5 years. The 10 recipients diagnosed early (stage I or II) had
significantly longer survival after cancer diagnosis than the 13 diagnosed at
an advanced stage (stage III or IV) (96.0 mo vs 9.0 mo, p <.001). In all, 14
(60.8%) of the 23 recipients died of cancer within 2 years after diagnosis, 12
(50.2%) within 12 months. The sum of the daily doses of immunosuppressive drugs
at cancer diagnosis was significantly greater for recipients who died within 2
years (p =.02). Furthermore, the difference in average doses of both prednisone
(p =.001) and azathioprine (p =.028) was also significantly greater for those
who died within 2 years. The average dose of cyclosporine was also greater, but
this difference did not reach statistical significance (p =.18). The average
dose of prednisone was significantly lower for recipients diagnosed early (p
=.001). This correlation between high immunosuppressive drug doses and worse
outcome has not been shown previously. CONCLUSIONS: Solid organ transplant
recipients who are diagnosed with advanced head and neck cancer while receiving
high doses of immunosuppressive drugs fare extremely poorly. High doses of
immunosuppressive drugs, most notably prednisone, correlate significantly with
advanced diagnosis of head and neck cancer and earlier death. N. Ref:: 30
----------------------------------------------------
[52]
TÍTULO / TITLE: - Stent-based
antirestenotic coatings (sirolimus/paclitaxel).
REVISTA
/ JOURNAL: - Catheter Cardiovasc Interv 2002 Mar;55(3):404-8.
●●
Enlace al texto completo (gratuito o de pago) 1002/ccd.10034 [pii]
AUTORES
/ AUTHORS: - Oberhoff M; Herdeg C; Baumbach A; Karsch
KR
INSTITUCIÓN
/ INSTITUTION: - Bristol Heart Institute, University of
Bristol, Bristol, U.K. martin.oberhoff@bristol.ac.uk N. Ref:: 49
----------------------------------------------------
[53]
TÍTULO / TITLE: - Single-agent
immunosuppression after liver transplantation: what is possible?
REVISTA
/ JOURNAL: - Drugs 2002;62(11):1587-97.
AUTORES
/ AUTHORS: - Raimondo ML; Burroughs AK
INSTITUCIÓN
/ INSTITUTION: - Liver Transplantation and Hepato-Biliary
Medicine, Royal Free Hospital, Hampstead, London, UK.
RESUMEN
/ SUMMARY: - Orthotopic liver transplantation is a life
saving and life enhancing procedure. The development of immunosuppressive drugs
has contributed to the high rate of success in terms of both patient and graft
survival. However, the considerable adverse effects of these therapies are
affecting long-term outcomes of transplant recipients. Complications related to
immunosuppression are responsible for the majority of deaths in patients
surviving more than 1 year. Therefore, the search for an optimal immunosuppressive
regimen has become of paramount importance. The liver has proved to be an
‘immunologically privileged’ organ, capable in several animal models to be
accepted as an allograft without any intervention on the immune system of the
recipient. In some human liver allografts acceptance of the new organ is
recognised after withdrawal of immunosuppressants, but prior identification of
such individuals is not yet possible, thus negating this management option.
Graft-recipient interaction is peculiar in liver transplantation: acute
cellular rejection does not always need to be treated, and if it is not severe,
appears to be associated with a better survival of both patient and graft. In
the last decade there has been an evolution of immunosuppressive protocols,
driven by empirical observation and a deeper understanding of immunological
events after transplant. However, most modifications have been made because of
the necessity to reduce long-term drug related morbidity and mortality.
Withdrawal of corticosteroids has proven to be safely achievable in most
patients, with no deleterious effects on patient or graft survival but with a
great benefit in terms of reduction of incidence of metabolic and
cardiovascular complications. Long-term ‘steroid-free’ regimens are therefore
now widely used. Patients with stable graft function can be easily maintained
using a single drug usually after 6 or 12 months and usually with a calcineurin
inhibitor. The more evolved step of using monotherapy ab initio has also proven
to be effective in a few studies and needs to be explored further. In the
future new strategies will be designed to help the development of tolerance of
the allograft, selectively stimulating instead of suppressing the immune
reaction of the recipient. N.
Ref:: 51
----------------------------------------------------
[54]
TÍTULO / TITLE: - Induction of
donor-specific tolerance in rat hind-limb allografts under antilymphocyte serum
and cyclosporine A protocol.
REVISTA
/ JOURNAL: - J Hand Surg [Am] 2002 Nov;27(6):1095-103.
●●
Enlace al texto completo (gratuito o de pago) 1053/jhsu.2002.36524
AUTORES
/ AUTHORS: - Siemionow M; Oke R; Ozer K; Izycki D;
Prajapati R
INSTITUCIÓN
/ INSTITUTION: - Department of Plastic Surgery,
Microsurgery Research, The Cleveland Clinic Foundation, Cleveland, OH 44195,
USA.
RESUMEN
/ SUMMARY: - Composite tissue allograft (CTA)
transplantation became a clinical reality despite major side effects associated
with the administration of chronic immunosuppression. Development of new
treatment modalities eliminating life-long immunosuppression is essential for
the future of CTA transplantation. In this study, combined use of cyclosporine
A (CsA) and antilymphocyte serum (ALS) was tested for the potential to induce
tolerance in the rat hind-limb allograft recipients across a major
histocompatibility (MHC) barrier (Lewis-Brown-Norway [LBN, RT1(l+n)] to Lewis
[LEW, RT1(l)] rats). Thirty transplantations were performed in 5 experimental
groups. Animals received CsA and ALS 12 hours before surgery for 21 days
thereafter. Although the allograft controls rejected their limbs at day 7
combined treatment of CsA and ALS resulted in indefinite survival (over 420 d)
in all allograft recipients. Long-term survivors showed 35% to 42% of
donor-specific chimerism in the peripheral blood. Clinical tolerance was
confirmed by acceptance of the donor-specific skin grafts and immunocompetence
was confirmed by rejection of the third-party grafts. Mixed lymphocyte reaction
revealed suppressed response against donor-type antigens and increased response
to third-party antigens. Donor-specific tolerance across MHC barrier was
induced in CTA allografts under 21 days protocol of ALS/CsA.
----------------------------------------------------
[55]
TÍTULO / TITLE: - Drug-eluting stent: the
“magic bullet” for prevention of restenosis?
REVISTA
/ JOURNAL: - Basic Res Cardiol 2002 Nov;97(6):417-23.
●●
Enlace al texto completo (gratuito o de pago) 1007/s00395-002-0379-2
AUTORES
/ AUTHORS: - Hehrlein C; Arab A; Bode C
INSTITUCIÓN
/ INSTITUTION: - Medizinische Universitatsklinik III, Abt
fur Kardiologie und Angiologie, Hugstetterstr 55, 79106 Freiburg i Br, Germany.
hehrlein@med1.ukl.uni-freiburg.de
RESUMEN
/ SUMMARY: - The need for repeat interventions after
initially successful PTCA due to restenosis has been called the “Archilles
heel” of a percutaneous revascularization procedure. The incidence of
restenosis varies between 20-50 % depending on the stent material, the presence
of risk factors, and the location of vascular disease. Some risk factors such
as diabetes have been clearly identified, others are currently debated. After
years of failures trying to reduces restenosis rates, locally administered
antiproliferative means have been shown to successfully inhibit excessive cell
growth in response to PTCA. Local radiotherapy of in-stent restenosis results
in a reduction of recurrent stenosis versus a conventional PTCA procedure.
However, long-term evaluation indicated that restenosis may only be delayed
with radiation therapy. Moreover, the restenosis rates were reduced, but the
restenotic process was not eliminated. Coronary stents eluting the
anti-proliferative agent rapamycin have demonstrated for the first time, that
restenosis rates of zero percent are achievable after percutaneous
revascularization procedures. Thus, it is intriguing to believe that the
elimination of restenosis may have become reality. The purpose of this review
is to discuss, whether a stent eluting drugs should be considered as the “magic
bullet” for prevention of restenosis after PTCA. N. Ref:: 88
----------------------------------------------------
[56]
TÍTULO / TITLE: - Sirolimus (Rapamune) in
renal transplantation.
REVISTA
/ JOURNAL: - Curr Opin Nephrol Hypertens 2002
Nov;11(6):603-7.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.mnh.0000040045.55337.97
AUTORES
/ AUTHORS: - Johnson RW
INSTITUCIÓN
/ INSTITUTION: - Manchester Postgraduate Health Sciences Centre,
Manchester Royal Infirmary, Manchester.
RESUMEN
/ SUMMARY: - There has been a necessary change in
attitude to transplantation; there is much less concern with short-term outcome
and more concern with long-term kidney function, overall health and quality of
life. Nephrotoxicity is an invariable consequence of long-term treatment with
calcineurin antagonists and it is one of the most underestimated causes of late
graft loss; it has been reported as a serious threat to both patient and graft
survival following heart, liver and bone marrow transplantation. Sirolimus has
been shown in many recent studies to be of great value in allowing patients to
be weaned from cyclosporine with excellent patient and graft survival at 24
months a significant improvement in renal function with resolution of hirsutism
and gum hyperplasia. Patients maintained on the combined regime of cyclosporine
and sirolimus had significantly higher blood pressure, much more cyclosporine
nephrotoxicity and hyperuricaemia at 12 months. The experimental studies have
found cyclosporine and sirolimus potentiate with each other’s good and adverse
effects. Cyclosporine therefore augments hyperlipidaemia caused by sirolimus,
and sirolimus augments nephrotoxicity caused by cyclosporine. The results of
these studies indicate that sirolimus is a suitable replacement for
cyclosporine or tacrolimus for long-term maintenance therapy. By contrast the
use of sirolimus in combination with cyclosporine results in potentiation of
side effects. The principal disadvantages being increased cyclosporine
associated nephrotoxicity and sirolimus associated hyperlipidaemia N. Ref:: 32
----------------------------------------------------
[57]
TÍTULO / TITLE: - Polyomavirus BK
nephropathy: a (re-)emerging complication in renal transplantation.
REVISTA
/ JOURNAL: - Am J Transplant 2002 Jan;2(1):25-30.
AUTORES
/ AUTHORS: - Hirsch HH
INSTITUCIÓN
/ INSTITUTION: - Department of Internal Medicine,
University of Basel, Switzerland. hans.hirsch@unibas.ch
RESUMEN
/ SUMMARY: - Persisting polyomavirus replication is now
widely recognized as a (re-)emerging cause of renal allograft dysfunction. Up
to 5% of renal allograft recipients can be affected about 40weeks (range 6-150)
post-transplantation. Progression to irreversible failure of the allograft has
been observed in up to 45% of all cases. The BK virus strain is involved in the
majority of the cases. Risk factors may include treatment of rejection episodes
and increasing viral replication under potent immunosuppressive drugs such as
tacrolimus, sirolimus or mycophenolate. The diagnosis requires the histological
demonstration of nuclear polyomavirus inclusions in affected tubular epithelial
cells. Interstitial inflammatory infiltrates and fibrosis become more prominent
in the persisting disease and may be difficult to distinguish from (coexisting)
rejection. Detection of polyomavirus-inclusion bearing cells (‘decoy cells’) in
the urine and quantification of BK virus DNA in the plasma have been proposed
as surrogate markers for polyomavirus replication and allograft disease,
respectively. Antiviral treatment is not yet established; however, reports of
treatment with cidofovir are encouraging. Current management aims at the judicious
modification and/or reduction of immunosuppression which, in view of preceding
or concurrent rejection, is not without risk.
N. Ref:: 51
----------------------------------------------------
[58]
TÍTULO / TITLE: - Drug-induced thrombotic
microangiopathy: incidence, prevention and management.
REVISTA
/ JOURNAL: - Drug Saf. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.csmwm.org/
●●
Cita: Drug Safety: <> 2001;24(7):491-501.
AUTORES
/ AUTHORS: - Pisoni R; Ruggenenti P; Remuzzi G
INSTITUCIÓN
/ INSTITUTION: - Department of Kidney Research, Mario Negri
Institute for Pharmacological Research, Bergamo, Italy.
RESUMEN
/ SUMMARY: - The term thrombotic microangiopathy (TMA)
describes syndromes characterised by microangiopathic haemolytic anaemia,
thrombocytopenia and variable signs of organ damage due to platelet thrombi in
the microcirculation. In children, infections with Shigella dysenteriae type 1
or particular strains of Escherichia coli are the most common cause of TMA; in
adults, a variety of underlying causes have been identified, such as bacterial
and viral infections, bone marrow and organ transplantation, pregnancy, immune
disorders and certain drugs. Although drug-induced TMA is a rare condition, it
causes significant morbidity and mortality. Antineoplastic therapy may induce
TMA. Most of the cases reported are associated with mitomycin. TMA has also
been associated with cyclosporin, tacrolimus, muromonab-CD3 (OKT3) and other
drugs such as interferon, anti-aggregating agents (ticlopidine, clopidogrel)
and quinine. The early diagnosis of drug-induced TMA may be vital. Strict
monitoring of renal function, urine and blood abnormalities, and arterial
pressure has to be performed in patients undergoing therapy with potentially
toxic drugs. The drug must be discontinued immediately in the case of suspected
TMA. Treatment modalities sometimes effective in other forms of TMA have been
used empirically. Although plasma exchange therapy seems to be of value, the
effectiveness of this approach has yet to be proved in multicentre, randomised
clinical studies. N.
Ref:: 113
----------------------------------------------------
[59]
TÍTULO / TITLE: - Induction versus
non-induction protocols in anti-calcineurin-based immunosuppression.
REVISTA
/ JOURNAL: - Transplant Proc 2001
Nov-Dec;33(7-8):3334-6.
AUTORES
/ AUTHORS: - Charpentier B
INSTITUCIÓN
/ INSTITUTION: - Service de Nephrologie, University
Hospital of Bicetre, Bicetre, France.
----------------------------------------------------
[60]
TÍTULO / TITLE: - Nephrotoxicity of
immunosuppressive drugs: new insight and preventive strategies.
REVISTA
/ JOURNAL: - Curr Opin Crit Care 2001 Dec;7(6):384-9.
AUTORES
/ AUTHORS: - Olyaei AJ; de Mattos AM; Bennett WM
INSTITUCIÓN
/ INSTITUTION: - Division of Nephrology, Hypertension and
Clinical Pharmacology, Oregon Health Sciences University and Solid Organ and
Cellular Transplantation, Legacy Good Samaritan Hospital, Portland, Oregon
97201, USA. olyaeia@ohsu.edu
RESUMEN
/ SUMMARY: - Cyclosporine and tacrolimus reduce
allograft rejection, improve allograft half-life and patient survival.
Ironically, the nephrotoxicity of these agents may adversely affect allograft
survival in renal transplant recipients or cause end-stage renal diseases in
other solid organ and bone marrow transplant recipients. Acute dose-dependent
and chronic non-dose-dependent nephrotoxicity has been reported in both
transplant recipients and patients with autoimmune disorders. Preliminary
evidence suggests that drug therapeutic monitoring has little value in the
diagnosis or management of nephrotoxicity associated with calcineurin
inhibitors. Although the exact mechanism of nephrotoxicity is not fully
understood, several factors have been implicated in the pathogenesis of
immunosuppressive-induced nephrotoxicity. Renal and systemic vasoconstriction,
increased release of endothelin-1, decreased production of nitric acid and
increased expression of TGF-beta are the major adverse pathophysiologic
abnormalities of these agents. Reducing the dose of a calcineurin inhibitor, or
using protocols without calcineurin inhibition may ultimately minimize the risk
of drug toxicity and improve allograft and patient survival. New experiences
with non-nephrotoxic agents and protocols including mycophenolate and sirolimus
allow for early calcineurin inhibitor reduction or elimination without
increasing the risk of allograft rejection.
N. Ref:: 55
----------------------------------------------------
[61]
TÍTULO / TITLE: - Rejection-free protocol
using sirolimus-tacrolimus combination for pediatric renal transplant
recipients.
REVISTA
/ JOURNAL: - Transplant Proc 2002 Aug;34(5):1942-3.
AUTORES
/ AUTHORS: - El-Sabrout R; Weiss R; Butt F; Delaney V;
Qadir M; Hanson P; Butt K
INSTITUCIÓN
/ INSTITUTION: - Departments of Transplantation/Vascular
Surgery, New York Medical College, Valhalla, New York, USA.
----------------------------------------------------
[62]
TÍTULO / TITLE: - The limitations of
calcineurin and mTOR inhibitors: new directions for immunosuppressive
strategies.
REVISTA
/ JOURNAL: - Transplant Proc 2002 Feb;34(1):130-3.
AUTORES
/ AUTHORS: - Kahan BD
INSTITUCIÓN
/ INSTITUTION: - Division of Organ Transplantation,
Department of Surgery, The University of Texas Medical School, Houston, Texas
77030, USA. N. Ref:: 76
----------------------------------------------------
[63]
TÍTULO / TITLE: - Can we prevent in-stent
restenosis?
REVISTA
/ JOURNAL: - Curr Opin Cardiol 2002 Sep;17(5):518-25.
AUTORES
/ AUTHORS: - Garza L; Aude YW; Saucedo JF
INSTITUCIÓN
/ INSTITUTION: - Division of Cardiovascular Medicine,
University of Arkansas for Medical Sciences, Little Rock, 72205, USA. garzaluis@uams.edu
RESUMEN
/ SUMMARY: - Nowadays stent placement has replaced
balloon angioplasty as the most commonly performed percutaneous coronary
interventional procedure, mainly because of its better acute and chronic
outcome. As a result, in-stent restenosis (ISR) has become a widespread
problem. The incidence of ISR varies from 10% to 50% and depends on the absence
or presence of several risk factors, such as small vessel size, longer lesions,
and diabetes. Intravascular ultrasound studies have demonstrated that ISR is
mainly caused by neointimal proliferation; consequently, this pathologic
process has become the target of many preventive and therapeutic approaches.
This article provides an overview of such management strategies, highlighting
the rather disappointing experiences with mechanical and systemic drug
therapies; the relative merits and disadvantages of intracoronary radiation;
and the exciting yet realistic promise, embodied by the recent advancements in
drug-eluting stent technology, of potentially eradicating ISR in the near
future. N. Ref:: 90
----------------------------------------------------
[64]
TÍTULO / TITLE: - Treatment of transplant
rejection: are the traditional immunosuppressants good enough?
REVISTA
/ JOURNAL: - Curr Opin Investig Drugs 2001
Mar;2(3):357-63.
AUTORES
/ AUTHORS: - Dumont FJ
INSTITUCIÓN
/ INSTITUTION: - Department Immunology & Rheumatology, Merck Research Laboratories,
Rahway, NJ 07065, USA. francis_dumont@merck.com
RESUMEN
/ SUMMARY: - Due to the improvement in the
understanding of the anti-allogenic immune response, the success of
transplantation medicine has increased rapidly over the last two decades. The
knowledge that the T-lymphocyte played an integral role in transplant
rejection, brought cyclosporine A and FK-506 to the fore as therapeutic
immunosuppressants. However, the current mainstays in transplant rejection are
not without their problems and many drug companies are exploring the
possibilities of improving the available therapies by developing drugs with
reduced toxicity, improved long-term survival and efficacy against chronic
rejection and improved immunosuppressive selectivity. The advances in the
understanding of T-cell activation and lymphocyte trafficking has highlighted
ways to improve the existing therapies and more selective immunosuppressant
targets. N. Ref:: 60
----------------------------------------------------
[65]
TÍTULO / TITLE: - Place of mycophenolate
mofetil in renal transplantation.
REVISTA
/ JOURNAL: - Transplant Proc 2001
Feb-Mar;33(1-2):997-9.
AUTORES
/ AUTHORS: - Grinyo JM
INSTITUCIÓN
/ INSTITUTION: - Hospital de Bellvitge, Barcelona,
España. N. Ref:: 23
----------------------------------------------------
[66]
TÍTULO / TITLE: - Hepatitis C and the
incidence of diabetes mellitus after renal transplant: influence of new
immunosuppression protocols.
REVISTA
/ JOURNAL: - Transplant Proc 2003 Aug;35(5):1748-50.
AUTORES
/ AUTHORS: - Gentil MA; Lopez M; Gonzalez-Roncero F;
Rodriguez-Algarra G; Pereira P; Lopez R; Martinez M; Toro J; Mateos J
INSTITUCIÓN
/ INSTITUTION: - Servicio de Nefrologia, Hospital
Universitario Virgen del Rocio, Sevilla, España.
RESUMEN
/ SUMMARY: - BACKGROUND: Hepatitis C has been
associated with an increased incidence of diabetes mellitus (DM) following
renal transplantation (RT). METHODS: Patients who underwent RT between 1985 and
2001 were excluded if they showed DM prior to RT, graft survival of less than
90 days, and unknown anti-HCV status (n=15). Two groups (G1 and G2) were
distinguished according to the immunosuppressive regimen: G1 (transplanted
1985-1996) received steroids, azathioprine, and cyclosporine (n=330), whereas
G2 (1997-2000) received new drugs in several combinations (MMF in 87% and/or
tacrolimus in 35% [n=240]). Patients with HCV antibodies pre- and/or post-RT
were considered HCV-positive. Post-RT DM requiring prolonged treatment with
oral antidiabetics or insulin (>1 month) was assessed using Kaplan-Meier curves
and Cox analysis. RESULTS: G2 patients were significantly older, had a greater
body mass index (BMI), and suffered significantly less from acute rejection
episodes during the first year than G1 patients. Furthermore, fewer required
maintenance steroids. HCV-positivity was more common in G1 than in G2 (n=96,
29.1% vs n=27, 11.3%). Six G2 patients were successfully treated with
interferon pre-RT, achieving negative PCR-HCV status (maintained post-RT). DM
incidence at 4 years was similar in G1 and G2 (8.8% and 8.2%). G1 HCV-positive
patients showed a greater risk of developing DM than HCV-negative patients
(28.0% vs 6.2% at 10 years; P=001). In G1, multivariate analysis showed that
age, BMI, and HCV-positivity were significant risk factors predicting DM (relative
risk, 5.7; 95% confidence interval 2.7-12). In G2 patients, HCV was not
associated with an increased risk of DM; in the multivariate analysis only age
appeared to be a risk factor. CONCLUSIONS: The reported relationship between
hepatitis C and post-RT DM was not observed among patients receiving new
immunosuppressive treatments. Confirmation of this finding requires extended
follow up. The reduced use of steroids and effective pre-RT use of interferon
may also be responsible for the benefit.
----------------------------------------------------
[67]
TÍTULO / TITLE: - Pediatric heart
transplantation.
REVISTA
/ JOURNAL: - Curr Opin Pediatr 2002 Oct;14(5):611-9.
AUTORES
/ AUTHORS: - Boucek Jr RJ; Boucek MM
INSTITUCIÓN
/ INSTITUTION: - All Children’s Hospital, University of
South Florida, St. Petersburg, Florida, 33701, USA. boucekr@allkids.org
RESUMEN
/ SUMMARY: - Heart transplantation is now a treatment
option with good outcome for infants and children with end-stage heart failure
or complex, inoperable congenital cardiac defects. One-year and 5-year
actuarial survival rates are high, approximately 75% and 65%, respectively,
with overall patient survival half-life greater than 10 years. To date, survival
has been improving as a result of reducing early mortality. Further reductions
in late mortality, in part because of graft coronary artery disease and
rejection, will allow achievement of the goal of decades-long survival. Quality
of life in surviving children, as judged by activity, is usually “normal.”
Somatic growth is usually at the low normal range but linear growth can be
reduced. Of infant recipients, 85% evaluated at 6 years of age or older were in
an age-appropriate grade level. Long-term management of childhood heart
recipients requires the collaboration of transplant physicians, given the
increasing number of immunosuppressive agents and the balance between rejection
and infection. Currently, recipients are maintained on immunosuppressive medications
that target calcineurin (eg, cyclosporine, tacrolimus), lymphocyte
proliferation (eg, azathioprine, mycophenolate mofetil [MMF], sirolimus) and,
in some instances antiinflammatory corticosteroids. Emerging evidence now
suggests a favorable immunologic opportunity for transplantation in childhood
and, conversely, a higher mortality rate in children who have had prior cardiac
surgery. Further studies are needed to define age-dependent factors that are
likely to play a role in graft survival and possible graft-specific tolerance
(eg, optimal conditions for tolerance induction and how immunosuppressive
regimens should be changed with maturation of the immune system). As late
outcomes continue to improve, the need for donor organs likely will increase,
as transplantation affords a better quality and duration of life for children
with complex congenital heart disease, otherwise facing a future of multiple
palliative operations and chronic heart failure. N. Ref:: 63
----------------------------------------------------
[68]
TÍTULO / TITLE: - Everolimus. Novartis.
REVISTA
/ JOURNAL: - Curr Opin Investig Drugs 2001
Sep;2(9):1220-34.
AUTORES
/ AUTHORS: - Dumont FJ
INSTITUCIÓN
/ INSTITUTION: - Merck Research Laboratories, Department of
Immunology & Rheumatology, 126 East Lincoln Avenue, PO Box 2000, Rahway, NJ
07065, USA. francis_dumont@merck.com
RESUMEN
/ SUMMARY: - Everolimus (RAD-001, SDZ RAD, Certican),
an analog of sirolimus, is an oral immunosuppressant that inhibits growth
factor-induced cell proliferation, under development by Novartis as a potential
treatment for transplant rejection. Phase III trials were initiated by the end
of 1998 [319337] and were ongoing in February 2001 [400448]. At the end of 2000,
Novartis was hoping to file for approval of the compound in 2001 [392881], with
a possible launch in mild-2002 [392881], [401979]. Completion of phase III
trials in heart transplant patients is expected this year and lung and liver
transplants by 2003. In 1999, American Home Products (AHP) initiated an action
for infringement of the patent EP-00401747, which covers the use of sirolimus
in transplantation in the UK, the Netherlands and Germany, seeking to restrain
the clinical trial program for everolimus. Novartis subsequently filed a
counterclaim for invalidity. In December 1999, the UK High Court of Justice
ruled that everolimus infringes the British counterpart of EP-00401747
[349637]. In contrast, in April 2000, the District Court of The Hague ruled that
everolimus does not infringe patent rights licensed to AHP [362823] and in July
2000, The Court of Appeal in the UK came to the same conclusion [376559]. In
February 2001, the Opposition Board at the European Patent Office upheld
Novartis’ European patent for everolimus, which the Board held to be
‘inventive’ [400448]. In July 2000, Vontobel estimated sales of SFr 80 million
in 2002, rising to SFr 800 million in 2004 [378871]. In February 2001, Merrill
Lynch predicted sales of SFr 125 million rising to SFr 661 million in 2005
[411704]. N. Ref:: 100
----------------------------------------------------
[69]
TÍTULO / TITLE: - Central pontine
myelinolysis.
REVISTA
/ JOURNAL: - Eur Neurol 2002;47(1):3-10.
AUTORES
/ AUTHORS: - Lampl C; Yazdi K
INSTITUCIÓN
/ INSTITUTION: - Department of Neurology, Psychiatry and
Pain Clinic, General Hospital Linz, Austria. christian.lampl@akh.linz.at
RESUMEN
/ SUMMARY: - Central pontine myelinolysis (CPM) is a
demyelinating disease of the pons often associated with demyelination of other
areas of the central nervous system (CNS). The term ‘osmotic demyelinization
syndrome’ is used for pontine and extrapontine myelinolysis. In this paper, we
are concerned with CPM although the extrapontine one is based on the same
pathogenesis. Both share the diagnostic methods, and their prevention and
therapy are the same. The etiology and pathogenesis of this disorder are
unclear and will be discussed. However, almost all cases of CPM are related to
severe diseases. Chronic alcoholism is still the most common underlying
condition of CPM patients. In the literature, 174 cases of CPM have been
reported in alcoholics since 1986, which is equivalent to an incidence of
39.4%. Likewise, 95 cases of CPM following the correction of hyponatremia have
been documented since 1986 (21.5%). The role of hyponatremia and its correction
will be outlined in the discussion of the pathogenesis of CPM. The third
largest group of CPM cases are liver transplant patients (17.4%), with the
development of CPM being attributed to the immunosuppressive agent cyclosporine
in particular. Depending on the involvement of other CNS structures, the
clinical picture can vary considerably. The large-scale introduction of magnetic
resonance imaging has increasingly facilitated the antemortem diagnosis of CPM,
although the radiological findings lag behind and do not necessarily correlate
with the clinical picture. As yet, there is no specific therapy of choice. A
number of therapeutic approaches have been tested and although they have not
been compared with regard to their rate of success, they have all led to a
substantial improvement in the prognosis of CPM. N. Ref:: 74
----------------------------------------------------
[70]
TÍTULO / TITLE: - Adverse
gastrointestinal effects of mycophenolate mofetil: aetiology, incidence and
management.
REVISTA
/ JOURNAL: - Drug Saf. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.csmwm.org/
●●
Cita: Drug Safety: <> 2001;24(9):645-63.
AUTORES
/ AUTHORS: - Behrend M
INSTITUCIÓN
/ INSTITUTION: - Abteilung fur Viszeral- und
Transplantationschirurgie, Medizinische Hochschule Hannover, Hannover, Germany.
Behrend.Matthias@MH-Hannover.de
RESUMEN
/ SUMMARY: - Mycophenolate mofetil (MMF) is a
relatively new immunosuppressive drug. It inhibits inosine monophosphate
dehydrogenase, a key enzyme in the de novo pathway of purine synthesis, and
thus causes lymphocyte-selective immunosuppression. Large clinical trials have
revealed the efficacy of MMF in the prevention of allograft rejection when administered
together with cyclosporin or tacrolimus and corticosteroids. Although the
adverse effect profile of MMF is comparatively benign, gastrointestinal adverse
effects are a major concern. These effects are partially explained by the
increased immune suppression, by the mode of action and by interactions,
particularly with other immunosuppressants. The aetiology of the rarest
gastrointestinal adverse effects is still not completely clear. Therapy depends
upon the clinical gravity of the adverse effects and is therefore a case of
waiting and ob- serving. An adjustment of dosage of immunosuppressants
according to the clinical situation and, particularly in the case of MMF,
spreading the total dosage over more than 2 daily doses are often sufficient.
Should adverse effects persist for a longer period of time and be of a more
serious nature, a comprehensive invasive diagnostic process is necessary,
including endoscopy and biopsy and the search for opportunistic infections. In
this case, dosage reduction or the complete withdrawal of MMF seems to be
unavoidable. Severe gastrointestinal complications with MMF are rare, but when
they do occur they may require extensive diagnosis and treatment. In the
future, therapeutic drug monitoring and, where necessary, pharmacological
modifications of MMF could lead to a further reduction of adverse effects with
an equal or even increased efficacy. N.
Ref:: 115
----------------------------------------------------
[71]
TÍTULO / TITLE: - Antiproliferative
coatings for the treatment of coronary heart disease:. what are the targets and
which are the tools?
REVISTA
/ JOURNAL: - J Interv Cardiol 2003 Dec;16(6):475-83.
AUTORES
/ AUTHORS: - Smith EJ; Rothman MT
INSTITUCIÓN
/ INSTITUTION: - London Chest Hospital, Barts and the London
NHS Trust, London, UK.
RESUMEN
/ SUMMARY: - Since the advent of percutaneous coronary
intervention (PCI) for stenosing coronary disease, restenosis has remained a
clinical problem. Despite the emergence and evolution of coronary stents, the
rate of restenosis following PCI is still 10-20%, and above 50% in high risk
subgroups. With increased understanding of the pathophysiology of this process,
a number of potential therapeutic targets have been identified, allowing the
development of novel therapies against restenosis, which can now be delivered
locally using stent platforms. Some of the reported clinical trial data
utilizing drug-eluting stents (DES) have produced such profound reductions in
clinical and angiographic restenosis that we have been tempted to believe we
are on the brink of eradicating this process completely. As the initial
excitement subsides, however, there is a need to decide whether these tools
will remain effective in real-world interventional practice. In this article we
review the pathophysiology of the restenotic process, and the biological
targets of the DES therapies currently available in clinical practice. We
attempt to define clinical target populations for DES therapy, and assess the
impact on outcomes thus far. We consider the advantages that newly emergent
stent coatings might offer, and whether targeting specific patient subgroups
with unique antiproliferative agents may provide the best chance of limiting
restenosis in high risk subgroups. Finally, we consider future strategies to
prevent restenosis, with a movement away from the antiproliferative approach,
and toward accelerating endothelialization.
N. Ref:: 41
----------------------------------------------------
[72]
TÍTULO / TITLE: - Pregnancy associated
aplastic anemia—a series of 10 cases with review of literature.
REVISTA
/ JOURNAL: - Hematology 2002 Aug;7(4):233-8.
●●
Enlace al texto completo (gratuito o de pago) 1080/1024533021000024067
AUTORES
/ AUTHORS: - Choudhry VP; Gupta S; Gupta M; Kashyap R;
Saxena R
INSTITUCIÓN
/ INSTITUTION: - Department of Hematology, All India
Institute of Medical Sciences, New Delhi 110029, India. vedpchoudhry@yahoo.co.in
RESUMEN
/ SUMMARY: - Introduction: Pregnancy induced aplastic
anemia is a rare entity and the association is not well explained. There are
approximately 80 cases in the literature and we are presenting the largest
series, so far, of 10 cases.Results: Total of 10 cases had 11 pregnancies. Mean
age at presentation was 25.45 years and mean gestation when symptoms first
developed was 17.09 weeks. Pallor and bleeding manifestations were the most
common presenting complaints. Mean Hb, TLC, ANC and platelets were 4.97 g/dl,
2.74 x 10(9)/l, 1.11 x 10(9)/l and 41 x 10(9)/l, respectively. Bone biopsy
cellularity ranged from <5 to 25%. Nine out of 11 (81%) pregnancies were
successful of which 7 was full term and 2 were premature. Two babies were small
for dates. One spontaneous abortion and one intra uterine death (IUD) were
observed. Two out of 11 mothers died due to disease after delivery. Two of the
8 surviving mothers, had spontaneous partial response (22%); 4 mothers were
asymptomatic after therapy with immunosuppressives given for 6 months and 3
were lost to follow up without response. Specific therapy (cyclosporin) was
tried in two mothers antenatally with partial response in one. One child whose
mother was given cyclosporin antenatally had jejunal atresia at birth.Conclusion:
Pregnancy associated aplastic anemia is a rare association. Spontaneous
remission can occur in 25-30% of patients. In the first trimester patients,
pregnancy can be terminated while in advanced pregnancy patients can be
followed up with stringent supportive care. Cyclosporin may be a safe drug
antenatally in such patients. Patients with established aplastic anemia should
avoid pregnancy. N.
Ref:: 23
----------------------------------------------------
[73]
TÍTULO / TITLE: - Prevention and treatment
of severe hemodynamic compromise in pediatric heart transplant patients.
REVISTA
/ JOURNAL: - Paediatr Drugs 2002;4(11):705-15.
AUTORES
/ AUTHORS: - Costello JM; Pahl E
INSTITUCIÓN
/ INSTITUTION: - Division of Pulmonary and Critical Care
Medicine, Department of Pediatrics, The Children’s Memorial Hospital, Feinberg
School of Medicine at Northwestern University, Chicago, Illinois 60614, USA.
RESUMEN
/ SUMMARY: - Allograft rejection is a leading cause of
severe hemodynamic compromise in pediatric heart transplant patients. A
triple-drug immunosuppression regimen, which includes a calcineurin inhibitor,
antiproliferative agent, and corticosteroid, suppresses the immune system at
multiple different levels for optimal graft protection while minimizing the
adverse effects of any one particular agent. Some pediatric centers also use
induction therapy with anti-T cell antibodies immediately following
transplantation as additional rejection prophylaxis. These antibodies augment
immunosuppression by either depleting the T cell pool or blocking interleukin-2
receptors on activated T cells. Despite the aggressive preventive measures
outlined above, some pediatric heart transplant patients will develop severe
hemodynamic compromise, most commonly due to fulminant rejection. Such patients
require attention to, and optimization of, the four determinants of cardiac
output (heart rate, preload, contractility and afterload) to stabilize the
circulation until the rejection can be reversed. Careful administration of volume,
diuretics, inotropes, and afterload-reducing agents will meet this goal.
Patients with allograft rejection require augmentation of immune suppression to
facilitate myocardial recovery. Corticosteroids form the cornerstone of
treatment for both cellular and vascular rejection. In patients with refractory
cellular rejection, conversion to mycophenolate mofetil or tacrolimus may be
appropriate if these agents are not already being used for maintenance
immunosuppression. Critically ill patients may additionally benefit from
muromonab-CD3 (OKT3) to augment lympholysis. Treatment employed specifically
for humoral rejection is prescribed with the intention of suppressing new
antibody formation, removing circulating antibody, and improving coronary blood
flow. In addition to corticosteroids, cyclophosphamide and antithymocyte
globulin or muromonab-CD3, along with plasmapheresis, may improve survival.
Systemic heparinization should be considered to minimize coronary thrombosis in
patients with humoral rejection. In the future, novel immunosuppressive agents
may further assist in the prevention as well as treatment of severe hemodynamic
compromise due to rejection in pediatric heart transplant recipients. N. Ref:: 99
----------------------------------------------------
[74]
TÍTULO / TITLE: - Treatment of
bifurcation coronary lesions: a review of current techniques and outcome.
REVISTA
/ JOURNAL: - J Interv Cardiol 2003 Dec;16(6):507-13.
AUTORES
/ AUTHORS: - Melikian N; Di Mario C
RESUMEN
/ SUMMARY: - Percutaneous treatment of coronary
bifurcation lesions, pose a number of technical challenges to the
interventional cardiologist. Each lesion has to be approached with its own,
targeted solution in the context of the clinical picture, anatomy, and
pathology. To achieve acceptable clinical outcomes a number of established
techniques are available. The exact anatomy of the lesion determines the
technique used. The most common approach is to stent the main vessel across the
ostium of the side branch. The side branch can be additionally treated with a
second stent or balloon angioplasty depending on the severity of the ostial
lesion and/or evidence of active ischemia. Other techniques involve stenting
the main branch up to the carina but sparing the side branches, multiple
‘kissing stent’ approaches (‘Y’,’T’, and ‘V’) or the ‘culottes’ technique.
Follow-up data demonstrates a high (over 90%) technical success rate. Clinical
outcome is variable but with conventional stents restenosis rates higher than
30% have been reported in most studies and there is no added advantage in
routine stenting of both main vessel and side branch. Recent introduction of
drug-eluting stents has resulted in a lower event rate and reduction of main
vessel restenosis in comparison with historical controls. Side branch ostial
restenosis remains a problem, which may require the development of novel
‘bifurcate’ stent designs to allow complete coverage with a single stent. N. Ref:: 36
----------------------------------------------------
[75]
TÍTULO / TITLE: - New developments in the
prophylaxis and treatment of graft versus host disease.
REVISTA
/ JOURNAL: - Expert Opin Pharmacother 2001
Jul;2(7):1109-17.
AUTORES
/ AUTHORS: - Simpson D
INSTITUCIÓN
/ INSTITUTION: - North Shore Hospital, Auckland, New
Zealand. david.simpson@whl.co.nz
RESUMEN
/ SUMMARY: - Graft versus host disease (GVHD) remains
the major obstacle to successful allogeneic bone marrow transplantation.
Cyclosporin with methotrexate is the most common prophylactic regimen.
Tacrolimus is associated with less GVHD and is gaining ground especially in
unrelated donor transplants where current regimens are unsatisfactory.
Mycophenolate mofetil (MMF) and rapamycin have not yet shown benefit in acute
GVHD prophylaxis. In vivo T-cell depletion with Campath 1H or thymoglobulin
used during transplant conditioning are increasingly used in place of ex vivo
T-cell depletion, where results remain disappointing. Steroids remain first
choice for therapy of GVHD but anti-CD25 antibodies, daclizumab or basiliximab
are gaining popularity as second-line therapy ahead of ATG. Chronic GVHD is
increasing with greater use of peripheral blood stem cell grafts and older
patients. The combination of tacrolimus and MMF is promising for patients with
extensive disease. Tolerance induction using CTLA-4-Ig, anti-CD40L, tresperimus
and/or rapamycin may revolutionise GVHD therapy. However, due to the
desirability of tumour intolerance, tolerance is likely to be developed in organ
transplantation before bone marrow transplantation for traditional indications.
Bone marrow transplants performed to induce organ tolerance may see increasing
use of these agents. TNF blockade using infliximab or etanercept (Enbrel) is
promising but the role of these agents is not yet defined. N. Ref:: 68
----------------------------------------------------
[76]
TÍTULO / TITLE: - Heat shock proteins:
novel therapeutic tools for HIV-infection?
REVISTA
/ JOURNAL: - Expert Opin Biol Ther 2001 Jan;1(1):67-77.
AUTORES
/ AUTHORS: - Brenner BG; Wainberg Z
INSTITUCIÓN
/ INSTITUTION: - McGill University, Montreal, Quebec,
Canada. bbrenn1@po-box.mcgill.ca
RESUMEN
/ SUMMARY: - Heat shock proteins (Hsps), cyclophilins
(Cyps) and FK binding proteins (FKBPs) form a family of intracellular chaperone
molecules that facilitate protein folding and assembly. These stress proteins
are selectively expressed in cells in response to a range of stimuli, including
heat, lymphokine and microbial/viral infections. This review discusses the role
of stress proteins in the HIV-1 viral life cycle, with regard to the
development of specific Hsp-based therapeutic strategies against HIV-1
infection. Cumulative findings are cited implicating CypA, Hsp27, Hsp70 and
FKBPs in host cell and viral activation, viral entry, assembly or formation of
infectious virions. Biological response modifiers that show specific
high-affinity interactions with Cyp, FKBPs and Hsps, including cyclosporins, FK-506
and cyclopentenone prostaglandins respectively, may block HIV-1 replication and
infection, providing novel HIV-1 therapeutic strategies. Moreover, Hsp binding
to viral complexes can enhance antiviral immunity, including natural killer
(NK), antibody-dependent (ADCC), gamma delta T-cell and cytotoxic T-lymphocyte
(CTL) activities against HIV-1 infected cells. The ability of Hsps to interact
with HIV-1 viral proteins, combined with their inherent adjuvant and
immunogenic properties indicates that Hsps may also serve as vehicles for
antigen delivery and the design of AIDS vaccines. N. Ref:: 94
----------------------------------------------------
[77]
TÍTULO / TITLE: - Strategies for
minimizing hyperlipidemia after cardiac transplantation.
REVISTA
/ JOURNAL: - Am J Cardiovasc Drugs 2002;2(6):377-87.
AUTORES
/ AUTHORS: - Kirklin JK; Benza RL; Rayburn BK; McGiffin
DC
INSTITUCIÓN
/ INSTITUTION: - Department of Surgery, Division of
Cardiothoracic Surgery, University of Alabama at Birmingham, Birmingham, Alabama
35294, USA. jkirklin@uab.edu
RESUMEN
/ SUMMARY: - Allograft coronary artery disease
represents a major limitation to long-term survival after cardiac
transplantation. Hyperlipidemias have been linked to the development of native
coronary atherosclerosis, and hyperlipidemic states have correlated with the
severity of allograft coronary artery disease. Heart transplant recipients
typically manifest increases in plasma levels of total cholesterol, low-density
lipoprotein-cholesterol (LDL-C), and triglycerides within the first 3-12 months
following transplantation. Factors known to promote post-transplant
hyperlipidemia include the use of corticosteroids, cyclosporine (interference
with clearance and increased oxidizability of LDL), sirolimus
(hypertriglyceridemia), and patient-specific causes of hyperlipidemia which
contributed to their underlying heart disease. Hydroxymethylglutaryl coenzyme-A
(HMG-CoA) reductase inhibitors are the foundation of antilipid therapy
following cardiac transplantation. Pravastatin is effective in lowering plasma
cholesterol levels and is associated with a decreased incidence and progression
of allograft coronary artery disease. All HMG-CoA reductase inhibitors except
pravastatin are metabolized by the hepatic cytochrome P450 system which
metabolizes cyclosporine, increasing the risk of myostitis when they are used
in large dosages with cyclosporine. Simvastatin, atorvastatin and fluvastatin
have been studied in heart transplant recipients. Gemfibrozil has proved
effective in transplant recipients when there is isolated marked elevation of
plasma triglyceride levels. When hyperlipidemia persists despite therapy, some
benefit may result with conversion from cyclosporine to tacrolimus. Although a
definitive link between hyperlipidemia and allograft coronary disease has yet
to be proven, available evidence points to abnormal lipid metabolism as part of
the complex etiologic machinery driving the process of ‘chronic rejection’.
Consensus exists within the transplant community that a HMG-CoA reductase
inhibitor such as pravastatin, should be part of the routine post-transplant
drug regimen, and persistent hyperlipidemia should be aggressively
treated. N. Ref:: 83
----------------------------------------------------
[78]
TÍTULO / TITLE: - Tresperimus: a new
agent for transplant tolerance induction.
REVISTA
/ JOURNAL: - Expert Opin Investig Drugs 2001
Jul;10(7):1381-6.
AUTORES
/ AUTHORS: - Simpson D
INSTITUCIÓN
/ INSTITUTION: - North Shore Hospital, Private Bag 93-503,
Takapuna, Auckland, New Zealand. david.simpson@whl.co.nz
RESUMEN
/ SUMMARY: - Tresperimus is a novel agent that induces
allogeneic transplant tolerance. It is structurally related to deoxyspergualin
(DSG) but has been modified to resist rapid hydrolysis in aqueous solution,
which simplifies administration. Despite this modification, tresperimus’s
actions in experimental models seem almost identical to DSG. Initially, DSG was
developed as an antitumour agent. Its antitumour efficacy appears limited but
DSG and tresperimus have favourable effects on transplant rejection. A short
course of tresperimus has been shown to have similar or greater quantitative
effects to cyclosporin in bone marrow, cardiac and skin transplant models.
However, qualitatively the effects are different. Prevention of rejection is
due to induction of donor-specific tolerance without affecting immunity to
third party antigens. In addition, CD4+ T-cells from tresperimus-treated
animals can transfer donor specific tolerance to naive animals, an effect not
seen with cyclosporin or other traditional immunosuppressive drugs. The
mechanism by which tolerance is induced is not clear. Tresperimus (like DSG)
binds to Hsc70, which among other effects inhibits nuclear localisation of
NF-kappa B. NF-kappa B nuclear localisation is induced by CD40 ligation in
antigen-presenting cells, an important early step in T-cell co-stimulation.
NF-kappa B is also required for CD28 ligation signalling, important in late
co-stimulation. It also is involved in B-cell activation, via CD40 ligation and
kappa light chain production. Hsc70 is also required for efficient cytosolic
peptide chaperoning to MHC class I molecules. Presumably, it is disruption of
T-cell/dendritic cell interaction that leads to induction of T-cell anergy.
Tresperimus is well-tolerated. The main dose limiting side effects are
orthostatic hypotension and peri-oral numbness. These effects are dependant on
blood drug levels and, due to its short half-life, correspond to the rate of
infusion. Phase II/III clinical studies are accruing patients and results have
not yet been reported. Tresperimus shows promise in the move from
immunosuppression to tolerance induction as the way to prevent transplant
rejection and graft versus host disease (G v HD). However, its role in
tolerance induction and effect in combination with other tolerance inducing
agents e.g., CTLA-4-Ig and anti-CD40L antibodies remains unclear. N. Ref:: 36
----------------------------------------------------
[79]
TÍTULO / TITLE: - Post-transplant
diabetes: incidence, relationship to choice of immunosuppressive drugs, and
treatment protocol.
REVISTA
/ JOURNAL: - Adv Ren Replace Ther 2001 Jan;8(1):64-9.
AUTORES
/ AUTHORS: - Markell MS
INSTITUCIÓN
/ INSTITUTION: - Division of Transplant Nephrology, State
University of New York, Downstate Medical Center, Brooklyn, NY 11203, USA. mmarkell@hscbklyn.edu
RESUMEN
/ SUMMARY: - Post-transplant diabetes mellitus (PTDM)
is one of the feared complications of immunosuppressive therapy. Despite
advances, including the introduction of the steroid-sparing calcineurin
inhibitors, cyclosporine and tacrolimus, the incidence rate remains greater
than 10% to 30%, especially in minority populations. PTDM increases the
subsequent risk of both graft loss and patient death, and predisposes patients
to all complications of diabetes, including retinopathy and neuropathy.
Patients should be monitored closely, especially during the first 3 months
post-transplant, and treated aggressively, should glucose intolerance be
detected. Minimization of immunosuppression dose, diet, oral hypoglycemic
agents, and insulin have all been used in the treatment of PTDM, however, the
insulin-sensitizing agents have not been studied. It is hoped that newer
immunosuppressive regimens and, ultimately, the ability to achieve tolerance
will eventually solve the problem of PTDM.
N. Ref:: 53
----------------------------------------------------
[80]
TÍTULO / TITLE: - Sirolimus: a
comprehensive review.
REVISTA
/ JOURNAL: - Expert Opin Pharmacother 2001
Nov;2(11):1903-17.
AUTORES
/ AUTHORS: - Kahan BD
INSTITUCIÓN
/ INSTITUTION: - Division of Immunology and Organ
Transplantation, University of Texas-Houston, 6431 Fannin, Suite 6.240,
Houston, TX 77030, USA. barry.d.kahan@uth.tmc.edu
RESUMEN
/ SUMMARY: - Sirolimus (Rapamune), Wyeth-Ayerst,
Madison, NJ) is a new, potent, immunosuppressant that is emerging as a
foundation for long-term immunosuppressive therapy in renal transplantation.
The drug acts during both co-stimulatory activation and cytokine-driven
pathways via a unique mechanism: inhibition of a multifunctional serine-threonine
kinase, mammalian target of rapamycin (mTOR). Although there is no a priori
reason to assume it, sirolimus displays a synergistic interaction to enhance
the efficacy of cyclosporin A (CsA). In trials wherein the concentrations of
CsA and sirolimus were tightly controlled, rates of acute rejection episodes
were < 10%, despite markedly reduced exposures to each agent. In pivotal
multi-centre blinded dose-controlled trials, the rates of acute rejection
episodes within 12 months following administration of 2 or 5 mg/day sirolimus
in combination with CsA and steroids were reduced to 19 and 14%, respectively.
Since the inhibitory effect of sirolimus disables virtually all responses to
cytokine mediators due to the widespread involvement of mTOR in multiple
signalling pathways, the agent is likely also to retard proliferation of
endothelial and vascular smooth muscle cells, an important component of the
immuno-obliterative processes associated with chronic rejection. The advantages
of this unique therapeutic action combined with an intrinsic lack of
nephrotoxicity are counterbalanced by myelosuppressive and hyperlipidaemic side
effects. Ongoing studies are assessing whether the long-term benefits of
sirolimus to permit reduction in exposure to or elimination of calcineurin
inhibitors ameliorate the progression of chronic nephropathy, the condition
that erodes long-term renal transplant survival. N. Ref:: 108
----------------------------------------------------
[81]
TÍTULO / TITLE: - New developments in immunosuppressive
therapy in renal transplantation.
REVISTA
/ JOURNAL: - Expert Opin Biol Ther 2002
Jun;2(5):483-501.
AUTORES
/ AUTHORS: - Gourishankar S; Turner P; Halloran P
INSTITUCIÓN
/ INSTITUTION: - Division of Nephrology and Immunology,
University of Alberta, Edmonton, Canada. gsita@hotmail.com
RESUMEN
/ SUMMARY: - The introduction of new immunosuppressive
agents and protocols has improved outcomes for renal transplant recipients by
decreasing the risk of rejection and by increasing the function and lifespan of
the allograft. This article reviews the major changes in the combinations of
therapies used: calcineurin inhibitors, target of rapamycin inhibitors,
mycophenolate mofetil, non-depleting monoclonal versus depleting monoclonal and
polyclonal antibodies for induction and increasing emphasis on protocols for
reduction or avoidance of steroids and calcineurin inhibitors. The new agents
with novel immunological targets such as anti-CD40 ligand, LEA29Y, FTY720,
anti-CD20 (rituximab, Rituxan, Mabthera) and anti-CH52 (alemtuzumab, Campath),
which are under development but have yet to survive the rigors of clinical
trials are also discussed. In the presence of low early rejection rates,
immunosuppressive therapy is setting new goals such as better graft function
(glomerular filtration rates), reduction in adverse effects such as
hypertension, hyperlipidaemia and drug toxicity and, above all, the prevention
of late graft deterioration. N.
Ref:: 156
----------------------------------------------------
[82]
TÍTULO / TITLE: - Synergy of passive
coating and targeted drug delivery: the tacrolimus-eluting Janus CarboStent.
REVISTA
/ JOURNAL: - J Interv Cardiol 2003 Dec;16(6):499-505.
AUTORES
/ AUTHORS: - Bartorelli AL; Trabattoni D; Fabbiocchi F;
Montorsi P; de Martini S; Calligaris G; Teruzzi G; Galli S; Ravagnani P
INSTITUCIÓN
/ INSTITUTION: - Centro Cardiologico Monzino IRCCS,
Institute of Cardiology, University of Milan, Milan, Italy. albartorelli@cardiologicomonzino.it
RESUMEN
/ SUMMARY: - Stents represent a major step forward in
the treatment of coronary artery disease since the introduction of balloon
angioplasty. They have demonstrated the reduction of angiographic indexes of
restenosis and rates of repeat revascularization. However, in-stent neointimal
proliferation represents the persisting limitation and challenge. Local
delivery using a stent platform for deposition of therapeutic drug concentration
in the arterial wall has emerged as an effective strategy to reduce in-stent
neointimal hyperplasia and restenosis. The purpose of this article is to
describe the design characteristics of a new drug-eluting stent. Its unique
features consist of integral Carbofilm thromboresistant coating combined with
the capability to load the drug into and to release it from deep sculptures
made on the external surface of the stent. The advantages of this design are
the possibility to load higher amounts of drug, to selectively deliver it to
the vessel wall without loss in the blood stream, and to improve the
biocompatibility and thromboresistance of the stent. Preclinical studies, using
tacrolimus as the biological agent, showed excellent vessel tissue response and
mild inflammation scores. A significant reduction of intimal proliferation was
observed in comparison with a control stent. The enrollment in a safety
first-in-man evaluation has been successfully completed. A randomized,
double-blind, multicenter study is expected to start at the completion of the
“safety” evaluation. N.
Ref:: 31
----------------------------------------------------
[83]
TÍTULO / TITLE: - Use of sirolimus in
kidney transplantation.
REVISTA
/ JOURNAL: - Prog Transplant 2001 Mar;11(1):29-32.
AUTORES
/ AUTHORS: - Podbielski J; Schoenberg L
INSTITUCIÓN
/ INSTITUTION: - University of Texas Medical School at
Houston, Houston, Tex., USA.
RESUMEN
/ SUMMARY: - Sirolimus, which has a distinctive
mechanism of action that inhibits cytokine-driven cell proliferation and
maturation, provides an exciting addition to the immunosuppressive regimen for
organ transplantation. A significant decrease in the number and severity of
rejection episodes has been noted when sirolimus is used; it also offers the potential
for patients to be withdrawn from steroids, making kidney transplantation an
option for many more potential recipients. Toxic conditions such as
hyperlipidemia, thrombocytopenia, and leukopenia become transient and
manageable with reduction of the sirolimus dose and/or countermeasure
therapy. N. Ref:: 9
----------------------------------------------------
[84]
TÍTULO / TITLE: - Sirolimus-eluting
stents: a review of experimental and clinical findings.
REVISTA
/ JOURNAL: - Z Kardiol 2002;91 Suppl 3:49-57.
AUTORES
/ AUTHORS: - Toutouzas K; Di Mario C; Falotico R;
Takagi T; Stankovic G; Albiero R; Corvaja N; Colombo A
INSTITUCIÓN
/ INSTITUTION: - Department of Interventional Cardiology,
Centro Cuore Columbus Via M. Buonarroti, 48 20145 Milan, Italy.
RESUMEN
/ SUMMARY: - Sirolimus (rapamycin), a macrolide
antibiotic with known potent immunosuppressive properties, acts in the first
phase (G1) of the cell cycle, blocking its further progression to the phase of
DNA synthesis (S). In experimental models, rapamycin is effective in inhibiting
smooth muscle cell proliferation and migration after vessel wall injury with
balloon angioplasty. These results lead to the clinical application of
sirolimus-eluting stents in 45 patients in Sao Paulo and Rotterdam (FIM
Registry) and 238 patients in a randomized, European multicenter trial (RAVEL).
These trials showed, by angiography and intravascular ultrasound, almost
complete abolition of in-stent late hyperplasia up to one year after the
procedure. In this review, we describe the experimental and clinical results of
sirolimus-eluting stents including our experience of 26 stents implanted in 17
patients. In elective de novo lesions has shown remarkably clear lumens at
follow-up angiography and intravascular ultrasound within the stented segments
were observed with no lesion progression at the stent margins or thrombosis
after a 2 month regimen of aspirin, and ticlopodine or clopidogrel. New
large-scale ongoing clinical trials will investigate the efficacy of sirolimus-eluting
stents in lesions that are traditionally associated with high restenosis rates
after stent implantation, such as long lesions, bifurcations and instent
restenosis. N. Ref:: 34
----------------------------------------------------
[85]
TÍTULO / TITLE: - Immunosuppressive
effects of beta-herpesviruses.
REVISTA
/ JOURNAL: - Herpes 2003 May;10(1):12-6.
AUTORES
/ AUTHORS: - Boeckh M; Nichols WG
INSTITUCIÓN
/ INSTITUTION: - Fred Hutchinson Cancer Research Center,
University of Washington, Seattle, WA, USA. mboeckh@fhcrc.org
RESUMEN
/ SUMMARY: - Immunomodulatory effects of human
beta-herpesviruses have been reported in vitro and in vivo. Clinical studies
suggest that beta-herpesvirus infection may increase the risk for other
infections, the severity of infection, or the tempo of disease progression. An
increased incidence of bacterial and fungal infections, and graft rejection,
have been reported in association with cytomegalovirus (CMV), and human
herpesviruses type 6 and type 7 infections have been implicated as risk factors
for CMV infection and graft rejection. Beta-herpesviruses may also interact
with HIV-1 and hepatitis C. To prove a causal relationship between
beta-herpesviruses and specific clinical outcomes, randomized trials, with
selective suppression of the virus, are required. Such trials have been
performed for CMV and showed a reduction in bacterial and fungal infections as
well as rejection in selected solid organ transplant recipients. More trials
are needed to evaluate whether the effects seen in observational studies are
truly related. N.
Ref:: 61
----------------------------------------------------
[86]
TÍTULO / TITLE: - Clinical experience
with drug-eluting stents.
REVISTA
/ JOURNAL: - Rev Cardiovasc Med 2002;3 Suppl 5:S31-7.
AUTORES
/ AUTHORS: - Drachman DE
INSTITUCIÓN
/ INSTITUTION: - Department of Medicine, (Knight Cardiac
Catheterization Laboratory, Cardiovascular Division, Massachusetts General
Hospital) Harvard Medical School, Boston, Massachusetts, USA.
RESUMEN
/ SUMMARY: - Despite dramatic improvements in catheter
and stent technology, in-stent restenosis continues to hamper initial
procedural success in 10% to 50% of patients undergoing coronary intervention.
Recent breakthroughs in polymer science and local drug delivery have shown
tremendous promise in the long-sought-after goal of delivering antirestenotic
therapy directly from a stent. Clinical trials examining several novel
antirestenotic agents, particularly sirolimus and paclitaxel, have shown
astonishing reduction in restenosis following stenting. Through examination of
the clinical experience to date, we may gain insight into the current and
future utility of drug-eluting stents in our clinical practice. N. Ref:: 21
----------------------------------------------------
[87]
TÍTULO / TITLE: - Initial experience with
paclitaxel-coated stents.
REVISTA
/ JOURNAL: - J Interv Cardiol 2002 Dec;15(6):471-5.
AUTORES
/ AUTHORS: - Grube E; Bullesfeld L
INSTITUCIÓN
/ INSTITUTION: - Heart-Center Siegburg, Ringstrasse 49,
53721 Siegburg, Germany. GrubeE@aol.com
RESUMEN
/ SUMMARY: - Local delivery of immunosuppressive or
antiproliferative agents using a drug-eluting stent is a new technology that is
supposed to inhibit in-stent restenosis, thus providing a biological and
mechanical solution. This technique is a very promising. To date, several
agents have been used, including paclitaxel, QP-2, rapamycin, actinomycin D,
dexamethason, tacrolimus, and everolimus. Several studies, published recently
or still ongoing, have evaluated these drugs as to their release kinetics,
effective dosage, safety in clinical practice, and benefit. These studies
include: SCORE (paclitaxel derivative), TAXUS I-VI, ELUTES, ASPECT, DELIVER
(paclitaxel), RAVEL, SIRIUS (sirolimus), ACTION (actinomycin), EVIDENT, PRESENT
(tacrolimus), EMPEROR (dexamethason), and FUTURE (everolimus). Paclitaxel was
one of the first stent-based antiproliferative agents under clinical investigation
that provided profound inhibition of neointimal thickening depending on
delivery duration and drug dosage. The randomized, multicenter SCORE trail
(Quanam stent, paclitaxel-coated) enrolled 266 patients at 17 sites. At
6-month’s follow-up, a drop of 83% in stent restenosis using the drug-eluting
stent could be achieved (6.4% drug-eluting stent vs 36.9% control group), which
was attributable to a remarkable decrease in intimal proliferation.
Unfortunately, due to frequent stent thrombosis and side-branch occlusions, the
reported 30-day MACE rate was 10.2%. The randomized TAXUS-I safety trial (BSC,
NIRx, paclitaxel-coated) also demonstrated beneficial reduction of restenotic
lesions at 6-month’s follow-up (0% vs 10%) but was associated with the absence
of thrombotic events presumably due to less drug dosage. The ongoing TAXUS
II-VI trials are addressing additional insight regarding the efficacy of the
TAXUS paclitaxel-eluting stent. ASPECT and ELUTES evaluated paclitaxel-coated
stents (i.e., Cook and Supra G), including subgroups with different drug
dosages. With respect to stent restenosis and neointimal proliferation, both
studies demonstrated a clear dose response. The RAVEL and the SIRIUS trials
evaluated sirolimus-coated stents (i.e., Cordis, Johnson & Johnson, and Bx
VELOCITY stents). Results confirmed the beneficial findings regarding reduction
of renarrowing using a drug-eluting stent without any major adverse effects.
Although parameters such as drug toxicity, optimal drug dosage, or delayed endothelial
healing still need to be evaluated, today’s clinical experience indicates that
drug-coated stents are extremely beneficial in the interventional treatment of
coronary lesions. N.
Ref:: 20
----------------------------------------------------
[88]
TÍTULO / TITLE: - Sirolimus eluting stent
in the treatment of atherosclerosis coronary artery disease.
REVISTA
/ JOURNAL: - Minerva Cardioangiol 2002
Oct;50(5):405-18.
AUTORES
/ AUTHORS: - Degertekin M; Regar E; Tanabe K; Lee CH;
Serruys PW
INSTITUCIÓN
/ INSTITUTION: - Department of Interventional Cardiology,
Thoraxcenter, Erasmus Medical Center, Rotterdam, The Netherlands.
RESUMEN
/ SUMMARY: - Stent implantation represents the most
commonly performed percutaneous coronary intervention nowadays. However,
instent restenosis due to exaggerated neointimal hyperplasia remains a problem
to overcome. Neointimal hyperplasia is a vascular response to stent injury; it
mainly consists of smooth muscle cells proliferation. The underlying molecular
mechanisms of restenosis were explained in this review article. Recently,
drug-eluting stent has been proposed as a potential method to prevent instent
restenosis. Animal studies have confirmed safety and efficacy of
sirolimus-eluting stent implantation in vivo. The FIM trial, which was the
first clinical study on sirolimus-eluting stent in de novo lesions, has shown
an astonishing 0% restenosis rate. The RAVEL trial was the first prospective,
double-blind, multi-center trial that randomized 238 patients at 19
institutions with de novo lesions into sirolimus-eluting versus bare Bx
velocity stent. Six-month binary restenosis rate in the sirolimus-group was
again 0% compared to 26.6% in the control group. Angiographic late loss and
major cardiac event were also significantly lower in the sirolimus-group. The
SIRIUS trial is an ongoing study conducted in 53 US centers that randomized
1100 patients with de novo lesion into sirolimus-eluting and bare stents.
Preliminary results also showed a significant reduction in binary restenosis,
late loss and repeat revascularization rates. Apart from de novo lesions, early
experience of sirolimus-eluting stent implantation for instent restenosis in
non-randomized study was also promising, achieving a single-digit repeat
restenosis rate. As compare with standard coronary stent, a sirolimus-eluting
stent shows considerable promise for the prevention of neointimal
proliferation, restenosis and associated clinical events. N. Ref:: 46
----------------------------------------------------
[89]
TÍTULO / TITLE: - Through the
drug-eluting stent labyrinth.
REVISTA
/ JOURNAL: - Ital Heart J 2003 Apr;4(4):236-45.
AUTORES
/ AUTHORS: - Guagliumi G; Musumeci G; Vassileva A;
Tespili M; Valsecchi O
INSTITUCIÓN
/ INSTITUTION: - Cardiovascular Department, Ospedali
Riuniti, Bergamo. guagliumig@interfree.it
RESUMEN
/ SUMMARY: - For interventional cardiologists
restenosis has represented the main limit for the successful long-term
treatment of coronary artery disease. The past 2 years witnessed the
extraordinary results of drug-eluting stents (DES), putting this technique at
the center stage. The safety and efficacy of sirolimus and paclitaxel-eluting
stents have been proved in large prospective, multicenter, randomized trials
(RAVEL, SIRIUS, TAXUS II). It is possible that the introduction of DES will
lead to substantial changes in the therapeutic and/or the economic strategies
of the treatment of ischemic coronary artery disease (increase in the
complexity of patients treated, reduction in surgical indications, growing
costs). Realizing the potential value of this technology will require the
successful management of more complex coronary situations (for lesions and
patients characteristics). Many extreme situations are still unexplored,
although for some of them studies are currently in progress or already being
planned. N. Ref:: 40
----------------------------------------------------
[90]
TÍTULO / TITLE: - Drug-eluting stents:
clinical experiences and perspectives.
REVISTA
/ JOURNAL: - Minerva Cardioangiol 2002
Oct;50(5):469-73.
AUTORES
/ AUTHORS: - Grube E; Gerckens U; Buellesfeld L
INSTITUCIÓN
/ INSTITUTION: - Heart Center Siegburg, Siegburg, Germany,
Italy. GrubeE@aol.com
RESUMEN
/ SUMMARY: - Drug-eluting stents (DES) have entered the
arena and are about to changed the landscape of Interventional Cardiology.
Today, the number of agents under preclinical and clinical investigation has
increased considerably, including drugs such as Paclitaxel, Sirolimus,
Tacrolimus, Everolimus, Dexamethasone, etc. Several studies have recently been
published or are still ongoing evaluating different stent designs with respect
to their safety and efficacy in treatment of coronary lesions. The SCORE trial
(Paclitaxel) revealed a significant reduction in restenosis at follow-up (FU)
in the drug-eluting stent group (6.4% vs 36.9% control group), attributable to
decreased intimal proliferation. However, stentthromboses and myocardial
infarctions, due to both stent design and high drug dosages, were observed
causing a MACE rate of 10.2% in the DES group. Confirming the beneficial
reduction of stent renarrowing using a local drug-eluting device, the rate of
restenosis in the TAXUS-I trial (Paclitaxel) was 0% at follow-up in patients
with DES vs 10% in patients with bare stents. Differences in MACE were not
observed, which underlined the potential impact of an optimal stent design.
First clinical experiences with a Sirolimus-coated stent (FIM trial)
demonstrated again a profound inhibition of neointimal ingrowth at 4-month
follow-up. The RAVEL trial, the first multicenter trial evaluating the
Sirolimus stent and the largest DES study published so far, confirmed the FIM
findings with a rate of restenosis in the DES group of 0% at 6 month FU. At 12
month FU, the beneficial impact on neointimal growth inhibition was persistent.
The pivotal study SIRIUS is addressed to evaluate this stent design more
extensively. However, given all the results being available today, local
application of anti-proliferative agents delivered by coronary stents is one of
the most promising techniques in treatment of coronary lesions. Nevertheless,
we need more trials and an agreement of definitions in order to evaluate this treatment
concept and eliminate unwanted side-effects.
N. Ref:: 8
----------------------------------------------------
[91]
TÍTULO / TITLE: - Modern strategies to
prevent coronary restenosis.
REVISTA
/ JOURNAL: - Ital Heart J 2002 Jun;3 Suppl 4:9S-15S.
AUTORES
/ AUTHORS: - Chieffo A; Stankovic G; Colombo A
INSTITUCIÓN
/ INSTITUTION: - Laboratory of Interventional Cardiology,
EMO Centro Cuore Columbus, Fondazione Centro San Raffaele del Monte Tabor,
Milan, Italy. N.
Ref:: 49
----------------------------------------------------
[92]
TÍTULO / TITLE: - Drug-eluting stent: the
emerging technique for the prevention of restenosis.
REVISTA
/ JOURNAL: - Minerva Cardioangiol 2002
Oct;50(5):443-53.
AUTORES
/ AUTHORS: - Sheiban I; Carrieri L; Catuzzo B; Destefanis
P; Oliaro E; Moretti C; Trevi GP
INSTITUCIÓN
/ INSTITUTION: - Interventional Cardiology, Division of
Cardiology, San Giovanni Battista Hospital, University of Turin, Turin, Italy. isheiban@yahoo.com
RESUMEN
/ SUMMARY: - Percutaneous coronary interventions (PCI)
have surpassed coronary artery bypass grafting as the most common means for
treating coronary artery disease, because of materials improvement, the use of
stent and pharmacotherapy. However, despite the variety of mechanical
techniques such as dilatation, debulking or conventional stent implantation,
the incidence of restenosis on short and mid-term follow-up is still
representing an important limitation to PCI. Restenosis is mainly due to
elastic recoil, negative vessel remodelling and neointimal proliferation, as a
response to vessel injury induced by angioplasty devices. The use of
conventional stents has provided an efficient method to avoid elastic recoil
and negative vessel remodelling, thus partially reducing restenosis as compared
to conventional balloon dilatation. However, neointimal proliferation
(biological vessel response to injury caused by stent implantation) is not
affected by stenting technique. Thus, the extensive use of coronary stent, even
in complex lesions, have produced again a “new” disease: the in-stent
restenosis especially in some patients’ subset (diabetics) or in some lesion
subset (bifurcations, long lesions, small vessels, total occlusions, diffuse
disease). Therefore, the main target of today’s interventional cardiologists is
to resolve this problem. The combination between mechanical control of elastic
recoil and negative remodelling (stent) and the control of neointimal
proliferation - biological response to vessel injury - (antiproliferative
drugs) is the emerging approach against restenosis. This emerging approach
consists in using the stent as drug carrier to the target site. Local delivery
of antiproliferative or immunosuppressive agents using a drug-coated stent is
supposed to inhibit in stent restenosis. The first antiproliferative agents
being used successfully in clinical trials are sirolimus and paclitaxel and, so
far, the data available of these trials demonstrated a marked reduction of
restenosis using sirolimus- and paclitaxel-coated stents as compared to
conventional stents. However, many questions are still to be answered and
several other clinical trials with drug-eluting stents are ongoing, evaluating
safety and efficacy of sirolimus and paclitaxel in a larger number of patients
and in different subset of coronary lesions type and morphology. Based on the
very impressive results available at the present time, we can expect, in the
very near future, remarkable changes in our clinical practice and the beginning
of a new “era” of interventional cardiology.
N. Ref:: 69
----------------------------------------------------
[93]
TÍTULO / TITLE: - Drug-eluting stents.
REVISTA
/ JOURNAL: - Minerva Cardioangiol 2002
Oct;50(5):419-29.
AUTORES
/ AUTHORS: - Chieffo A; Colombo A
INSTITUCIÓN
/ INSTITUTION: - Interventional Cardiology EMO, Centro
Cuore Columbus and San Raffaele Hospital, Milan, Italy.
RESUMEN
/ SUMMARY: - Drug-eluting stents represent the third
revolution in the field of Interventional Cardiology following balloon
angioplasty (PTCA) and the implantation of metal stents. The main limitation of
percutaneous coronary intervention (PCI) is restenosis. The introduction of
drug eluting stents able to release antiproliferative compounds led to the
evaluation of several antiproliferative drugs in order to reduce restenosis.
Rapamycin (Sirolimus) has been demonstrated to inhibit smooth muscle cell (SMC)
proliferation and migration in vitro and to reduce in vivo neointima formation
with blockage of the cell cycle progression at the G1-S transition. In a pilot
study, recently confirmed by a randomized trial, rapamycin drug-eluting stents
have been reported to eliminate restenosis after stent implantation. Promising
data also come from the use of paclitaxel drug-eluting stents. Paclitaxel
(Taxol) is a microtubule-stabilizing agent with potent antiproliferative
activity. Even if drug-eluting stents represent one of the most promising
fields in Interventional Cardiology today before being sure of their real
potential it is necessary to wait for results from several ongoing clinical
studies, their usage in real-world lesions and extended follow-up to 5
years. N. Ref:: 41
----------------------------------------------------
[94]
TÍTULO / TITLE: - Restenosis in
percutaneous coronary intervention—is drug-eluting stent the answer?
REVISTA
/ JOURNAL: - Singapore Med J 2003 Sep;44(9):482-7.
AUTORES
/ AUTHORS: - Lim VY; Lim YL
INSTITUCIÓN
/ INSTITUTION: - Division of Cardiology, Changi General
Hospital, 2 Simei Street 3, Singapore 529889. victor_lim@cgh.com.sg
RESUMEN
/ SUMMARY: - The long-term success of percutaneous
coronary intervention in the treatment of coronary artery disease is hampered
by the occurrence of restenosis, which often necessitates repeat
hospitalisations or coronary interventions. The advent of drug-eluting stents,
particularly those coated with sirolimus and paclitaxel, may be the
breakthrough in the battle against restenosis that interventional cardiologists
have been waiting for, and we review the currently available evidence for this.
Despite the growing enthusiasm, we should not forget that this new technology
is still in its relative infancy, and there remain many unanswered questions,
particularly about the long-term effect of using these stents. N. Ref:: 33
----------------------------------------------------
[95]
TÍTULO / TITLE: - Drug-eluting stents in
the treatment of atherosclerotic coronary heart disease.
REVISTA
/ JOURNAL: - Indian Heart J 2002 Mar-Apr;54(2):212-6.
AUTORES
/ AUTHORS: - Lemos PA; Regar E; Serruys PW
INSTITUCIÓN
/ INSTITUTION: - Department of Cardiology, Thoraxcentre,
Erasmus Medical Centre, Rotterdam. N.
Ref:: 47
----------------------------------------------------
[96]
TÍTULO / TITLE: - Drug-eluting stents to
prevent reblockage of coronary arteries.
REVISTA
/ JOURNAL: - J Cardiovasc Nurs 2003 Jan-Mar;18(1):11-6.
AUTORES
/ AUTHORS: - Schwertz DW; Vaitkus P
INSTITUCIÓN
/ INSTITUTION: - Department of Medical Surgical Nursing, University
of Illinois, Chicago, Illinois, USA.
RESUMEN
/ SUMMARY: - Restenosis limits the success of
percutaneous transluminal coronary interventions. Coronary artery stenting
decreases restenosis, improves outcomes, and is currently the most commonly used
percutaneous coronary intervention in the United States. However, in-stent
restenosis continues to occur at an unacceptable rate. In-stent restenosis is a
neointimal hyperplastic response resulting primarily from vascular smooth
muscle cell proliferation. Treatment with anti-proliferative agents presents a
logical approach to eradicating restenosis, however, these drugs are highly
toxic. Coating stents with anti-proliferative agents allows local delivery of
high doses and avoids systemic side effects. In 2001, the results of two
clinical trials, RAVEL and ELUTES, using sirolimus- and paclitaxil-coated
stents demonstrated nearly complete elimination of in-stent restenosis. These
dramatic results represent a tremendous advance in the treatment of coronary heart
disease. N. Ref:: 23
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