#08#
Revisiones-Clínica-Terapéutica
& Ensayos Clínicos *** Reviews-Clinical-Therapeutics & Clinical Trials
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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documento sólo contiene artículos escritos en Castellano y/o Inglés.
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Only articles written in Spanish and/or English are included.
[1]
TÍTULO / TITLE: - Dendritic cells:
emerging pharmacological targets of immunosuppressive drugs.
REVISTA
/ JOURNAL: - Nat Rev Immunol 2004 Jan;4(1):24-34.
●●
Enlace al texto completo (gratuito o de pago) 1038/nri1256
AUTORES
/ AUTHORS: - Hackstein H; Thomson AW
INSTITUCIÓN
/ INSTITUTION: - Institute for Clinical Immunology and
Transfusion Medicine, Justus-Liebig University Giessen, Langhansstr. 7, D-35392
Giessen, Germany. holger.hackstein@immunologie.med.uni-giessen.de
RESUMEN
/ SUMMARY: - Immunosuppressive drugs have
revolutionized organ transplantation and improved the therapeutic management of
autoimmune diseases. The development of immunosuppressive drugs and
understanding of their action traditionally has been focused on lymphocytes,
but recent evidence indicates that these agents interfere with immune responses
at the earliest stage, targeting key functions of dendritic cells (DCs). Here,
we review our present understanding of how classical and new immunosuppressive
agents interfere with DC development and function. This knowledge might provide
a rational basis for the selection of immunosuppressive drugs in different
clinical settings and for the generation of tolerogenic DCs in the
laboratory. N. Ref:: 116
----------------------------------------------------
[2]
- Castellano -
TÍTULO / TITLE:La ruta de senalizacion
CA++/calcineurina/NFAT en activacion endotelial y angiogenesis: efectos de la
ciclosporina A. CA++/ calcineurin/NFAT signaling in endothelial activation and
angiogenesis: effects od cyclosporin A .
REVISTA
/ JOURNAL: - Nefrologia. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.aulamedica.es/nefrologia/
●●
Cita: Nefrologia: <> 2003;23 Suppl 3:44-8.
AUTORES
/ AUTHORS: - Quesada AJ; Redondo JM
INSTITUCIÓN
/ INSTITUTION: - Centro de Biologia Molecular Severo Ochoa,
Consejo Superior de Investigaciones Cientificas, Universidad Autonoma de Madrid
y Centro Nacional de Investigaciones Cardiovasculares (CNIC), Sinesio Delgado,
4 28049 Cantoblanco, Madrid. jmredondo@cbm.uam.es N. Ref:: 31
----------------------------------------------------
[3]
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.
----------------------------------------------------
[4]
TÍTULO / TITLE: - Progress in the
treatment of rheumatoid arthritis.
REVISTA
/ JOURNAL: - JAMA. Acceso gratuito al texto completo.
●●
Enlace a la Editora de la Revista http://jama.ama-assn.org/search.dtl
●●
Cita: JAMA: <> 2001 Dec 12;286(22):2787-90.
AUTORES
/ AUTHORS: - Pisetsky DS; St Clair EW
INSTITUCIÓN
/ INSTITUTION: - Division of Rheumatology, Allergy, and
Clinical Immunology, Duke University Medical Center, 1516 Durham Veterans
Affairs Medical Center, Box 151G, Durham, NC 27710, USA. dpiset@acpub.duke.edu N. Ref:: 27
----------------------------------------------------
[5]
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
----------------------------------------------------
[6]
TÍTULO / TITLE: - A randomized long-term
trial of tacrolimus/sirolimus versus tacrolimus/mycophenolate mofetil versus
cyclosporine (NEORAL)/sirolimus in renal transplantation. II. Survival,
function, and protocol compliance at 1 year.
REVISTA
/ JOURNAL: - Transplantation 2004 Jan 27;77(2):252-8.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000101495.22734.07
AUTORES
/ AUTHORS: - Ciancio G; Burke GW; Gaynor JJ; Mattiazzi
A; Roth D; Kupin W; Nicolas M; Ruiz P; Rosen A; Miller J
INSTITUCIÓN
/ INSTITUTION: - Department of Surgery, Division of
Transplantation, University of Miami School of Medicine, Miami, FL 33101, USA. gciancio@med.miami.edu
RESUMEN
/ SUMMARY: - BACKGROUND: In an attempt to reduce
chronic calcineurin inhibitor induced allograft nephropathy in first cadaver
and human leukocyte antigen non-identical living-donor renal transplantation,
sirolimus (Siro) or mycophenolate mofetil (MMF) was tested as adjunctive
therapy, with planned dose reductions of tacrolimus (Tacro) over the first year
postoperatively. Adjunctive Siro therapy with a similar dose reduction
algorithm for Neoral (Neo) was included for comparison. METHODS: The detailed
dose reduction plan (Tacro and Siro, group A; Tacro and MMF, group B; Neo and
Siro, group C) is described in our companion report in this issue of
Transplantation. The present report documents function, patient and graft
survival, protocol compliance, and adverse events. RESULTS: As mentioned (in
companion report), group demographics were similar. The present study shows no
significant differences in 1-year patient and graft survival but does show a
trend that points to more difficulties in group C by way of a rising slope of
serum creatinine concentration (P=0.02) and decreasing creatinine clearance
(P=0.04). There were more patients who discontinued the protocol plan in group
C. Thus far, no posttransplant lymphomas have appeared, and infectious
complications have not differed among the groups. However, a greater percentage
of patients in group C were placed on antihyperlipidemia therapy, with an
(unexpected) trend toward a higher incidence of posttransplant diabetes
mellitus in this group. Group A required fewer, and group B the fewest,
antihyperlipidemia therapeutic interventions (P<0.00001). CONCLUSIONS: This
1-year interim analysis of a long-term, prospective, randomized
renal-transplant study indicates that decreasing maintenance dosage of Tacro
with adjunctive Siro or MMF appears to point to improved long-term function,
with reasonably few adverse events.
----------------------------------------------------
[7]
TÍTULO / TITLE: - Early outcome after
sirolimus-eluting stent implantation in patients with acute coronary syndromes:
insights from the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology
Hospital (RESEARCH) registry.
REVISTA
/ JOURNAL: - J Am Coll Cardiol 2003 Jun
4;41(11):2093-9.
AUTORES
/ AUTHORS: - Lemos PA; Lee CH; Degertekin M; Saia F;
Tanabe K; Arampatzis CA; Hoye A; van Duuren M; Sianos G; Smits PC; de Feyter P;
van der Giessen WJ; van Domburg RT; Serruys PW
INSTITUCIÓN
/ INSTITUTION: - Department of Cardiology, Thoraxcenter,
Erasmus Medical Center, Dr Molewaterplein 40, NL-3015 GD Rotterdam, the Netherlands.
RESUMEN
/ SUMMARY: - OBJECTIVES: This study evaluated the early
outcomes of patients with acute coronary syndromes (ACS) treated with
sirolimus-eluting stents (SES). BACKGROUND: The safety of SES implantation in
patients with a high risk for early thrombotic complications is currently
unknown. METHODS: Sirolimus-eluting stents have been utilized as the device of
choice for all percutaneous procedures in our institution, as part of the
Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH)
registry. After four months of enrollment, 198 patients with ACS had been
treated exclusively with SES (64% of those treated in the period) and were
compared with a control group composed of 301 consecutive patients treated with
bare stents in the same time period immediately before this study. The
incidence of major adverse cardiac events (MACE) during the first month was
evaluated (death, nonfatal myocardial infarction [MI], or re-intervention).
RESULTS: Compared with control patients, patients treated with SES had more
primary angioplasty (95% vs. 77%; p < 0.01), more bifurcation stenting (13%
vs. 5%; p < 0.01), less previous MI (28% vs. 45%; p < 0.01), and less
glycoprotein IIb/IIIa inhibitor utilization (27% vs. 42%; p < 0.01). The
30-day MACE rate was similar between both groups (SES 6.1% vs. control patients
6.6%; p = 0.8), with most complications occurring during the first week. Stent
thrombosis occurred in 0.5% of SES patients and in 1.7% of control patients (p
= 0.4). In multivariate analysis, SES utilization did not influence the
incidence of MACE (odds ratio 1.0 [95% confidence interval: 0.4 to 2.2]; p =
0.97). CONCLUSIONS: Sirolimus-eluting stent implantation for patients with ACS
is safe, with early outcomes comparable with bare metal stents. N. Ref:: 25
----------------------------------------------------
[8]
TÍTULO / TITLE: - The target of rapamycin
(TOR) proteins.
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 Jun 19;98(13):7037-44.
●●
Enlace al texto completo (gratuito o de pago) 1073/pnas.121145898
AUTORES
/ AUTHORS: - Raught B; Gingras AC; Sonenberg N
INSTITUCIÓN
/ INSTITUTION: - Department of Biochemistry and McGill
Cancer Centre, McGill University, 3655 Promenade Sir-William-Osler, Montreal,
QC H3G 1Y6 Canada.
RESUMEN
/ SUMMARY: - Rapamycin potently inhibits downstream
signaling from the target of rapamycin (TOR) proteins. These evolutionarily
conserved protein kinases coordinate the balance between protein synthesis and
protein degradation in response to nutrient quality and quantity. The TOR
proteins regulate (i) the initiation and elongation phases of translation, (ii)
ribosome biosynthesis, (iii) amino acid import, (iv) the transcription of
numerous enzymes involved in multiple metabolic pathways, and (v) autophagy.
Intriguingly, recent studies have also suggested that TOR signaling plays a
critical role in brain development, learning, and memory formation. N. Ref:: 132
----------------------------------------------------
[9]
TÍTULO / TITLE: - Rapamycin plays a new
role as differentiator of vascular smooth muscle phenotype. focus on “The
mTOR/p70 S6K1 pathway regulates vascular smooth muscle differentiation”.
REVISTA
/ JOURNAL: - Am J Physiol Cell Physiol. Acceso gratuito
al texto completo.
●●
Enlace a la Editora de la Revista http://ajpcell.physiology.org/contents-by-date.0.shtml
●●
Cita: Am J Physiol Cell Physiol: <> 2004 Mar;286(3):C480-1.
●●
Enlace al texto completo (gratuito o de pago) 1152/ajpcell.00526.2003
AUTORES
/ AUTHORS: - Lucchesi PA N. Ref:: 12
----------------------------------------------------
[10]
TÍTULO / TITLE: - CD3-specific
antibody-induced active tolerance: from bench to bedside.
REVISTA
/ JOURNAL: - Nat Rev Immunol 2003 Feb;3(2):123-32.
●●
Enlace al texto completo (gratuito o de pago) 1038/nri1000
AUTORES
/ AUTHORS: - Chatenoud L
INSTITUCIÓN
/ INSTITUTION: - Centre de l’Association Claude Bernard sur
les Maladies Autoimmunes and Hopital Necker Enfants Malades IRNEM, 161 Rue de
Sevres, 75015 Paris, France. chatenoud@necker.fr
RESUMEN
/ SUMMARY: - Although they were used initially as
non-specific immunosuppressants in transplantation, CD3-specific monoclonal
antibodies have elicited renewed interest owing to their capacity to induce
immune tolerance. In mouse models of autoimmune diabetes, CD3-specific
antibodies induce stable disease remission by restoring tolerance to pancreatic
beta-cells. This phenomenon was extended recently to the clinic—preservation of
beta-cell function in recently diagnosed patients with diabetes was achieved by
short-term administration of a CD3-specific antibody. CD3-specific antibodies
arrest ongoing disease by rapidly clearing pathogenic T cells from the target.
Subsequently, they promote long-term T-cell-mediated active tolerance. Recent
data indicate that transforming growth factor-beta-dependent CD4+CD25+
regulatory T cells might have a central role in this effect. N. Ref:: 117
----------------------------------------------------
[11]
TÍTULO / TITLE: - Neuroimmunophilins:
novel neuroprotective and neuroregenerative targets.
REVISTA
/ JOURNAL: - Ann Neurol 2001 Jul;50(1):6-16.
AUTORES
/ AUTHORS: - Guo X; Dillman JF 3rd; Dawson
VL; Dawson TM
INSTITUCIÓN
/ INSTITUTION: - Department of Neurology, The Johns Hopkins
University School of Medicine, Baltimore, MD 21287, USA.
RESUMEN
/ SUMMARY: - Cyclosporin A (CsA) and FK506 (tacrolimus)
are immunosuppresants that are widely used in organ transplantation. CsA is an
11-member cyclic peptide, whereas FK506 is a macrolide antibiotic. Recently,
these powerful and useful compounds have become of great interest to
neuroscientists for their unique neuroprotective and neuroregenerative effects.
These drugs and nonimmunosuppressive analogs protect neurons from the effects
of glutamate excitotoxicity, focal ischemia, and
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic cell
death. They also stimulate functional recovery of neurons in a variety of
neurologic injury paradigms. These drugs exert their effects via immunophilins,
the protein receptors for these agents. The immunophilin ligands show
particular promise as a novel class of neuroprotective and neuroregenerative
agents that have the potential to treat a variety of neurologic disorders. N. Ref:: 102
----------------------------------------------------
[12]
TÍTULO / TITLE: - Preliminary guidelines
for diagnosing and treating tuberculosis in patients with rheumatoid arthritis
in immunosuppressive trials or being treated with biological agents.
REVISTA
/ JOURNAL: - Ann Rheum Dis 2002 Nov;61 Suppl 2:ii62-3.
AUTORES
/ AUTHORS: - Furst DE; Cush J; Kaufmann S; Siegel J;
Kurth R
INSTITUCIÓN
/ INSTITUTION: - UCLA Medical School, Los Angeles, USA
Presbyterian Hospital, Dallas, USA.
----------------------------------------------------
[13]
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
----------------------------------------------------
[14]
TÍTULO / TITLE: - Overcoming restenosis
with sirolimus: from alphabet soup to clinical reality.
REVISTA
/ JOURNAL: - Lancet 2002 Feb 16;359(9306):619-22.
AUTORES
/ AUTHORS: - Poon M; Badimon JJ; Fuster V
INSTITUCIÓN
/ INSTITUTION: - Mount Sinai School of Medicine, 1 Gustav L
Levy Place, Box 1030, New York, NY 10029, USA.
N. Ref:: 34
----------------------------------------------------
[15]
TÍTULO / TITLE: - New agents in acute
myeloid leukemia and other myeloid disorders.
REVISTA
/ JOURNAL: - Cancer 2004 Feb 1;100(3):441-54.
●●
Enlace al texto completo (gratuito o de pago) 1002/cncr.11935
AUTORES
/ AUTHORS: - Ravandi F; Kantarjian H; Giles F; Cortes J
INSTITUCIÓN
/ INSTITUTION: - Department of Leukemia, The University of
Texas M D Anderson Cancer Center, Houston, Texas 77030, USA. fravandi@mdanderson.org
RESUMEN
/ SUMMARY: - Over the past several decades,
improvements in chemotherapeutic agents and supportive care have resulted in
significant progress in treating patients with acute myeloid leukemia (AML).
More recently, advances in understanding the biology of AML have resulted in
the identification of new therapeutic targets. The success of
all-trans-retinoic acid in acute promyelocytic leukemia and of imatinib
mesylate in chronic myeloid leukemia have demonstrated that targeted therapy
may be more effective and less toxic when well defined targets are available.
At the same time, understanding mechanisms of drug resistance and means to
overcome them has led to modification of some of the existing cytotoxic agents.
Rational design and conduct of clinical trials is necessary to ensure that the
full potential of these new agents is realized. N. Ref:: 140
----------------------------------------------------
[16]
TÍTULO / TITLE: - High-dose immune
suppression and autologous hematopoietic stem cell transplantation in
refractory Crohn disease.
REVISTA
/ JOURNAL: - Blood. Acceso gratuito al texto completo a
partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.bloodjournal.org/
●●
Cita: Blood: <> 2003 Mar 1;101(5):2064-6. Epub 2002 Oct 10.
●●
Enlace al texto completo (gratuito o de pago) 1182/blood-2002-07-2122
AUTORES
/ AUTHORS: - Burt RK; Traynor A; Oyama Y; Craig R
INSTITUCIÓN
/ INSTITUTION: - Division of Immunotherapy, Northwestern
University Medical School, Chicago, IL 60611, USA. rburt@nwu.edu
RESUMEN
/ SUMMARY: - Two patients with severe Crohn disease,
defined by a Crohn Disease Activity Index (CDAI) higher than 250 despite
anti-tumor necrosis factor alpha (TNF-alpha), were treated by intense immune
suppression and autologous hematopoietic stem cell transplantation (HSCT). Stem
cells were mobilized from the peripheral blood using cyclophosphamide (2.0
g/m2) and granulocyte colony-stimulating factor (G-CSF; 5 micro g/kg/d),
enriched ex vivo by CD34+ selection, and reinfused after immune conditioning
with cyclophosphamide (200 mg/kg) and equine anti-thymocyte globulin (ATG; 90
mg/kg). Patients have remained in remission (CDAI < 100) for 1 year since
HSCT. We conclude that further HSCT studies for severe Crohn disease appear
warranted. N. Ref:: 13
----------------------------------------------------
[17]
TÍTULO / TITLE: - Immunosuppressive and
cytotoxic therapy for pulmonary sarcoidosis.
REVISTA
/ JOURNAL: - Cochrane Database Syst Rev
2003;(3):CD003536.
●●
Enlace al texto completo (gratuito o de pago) 1002/14651858.CD003536
AUTORES
/ AUTHORS: - Paramothayan S; Lasserson T; Walters EH
INSTITUCIÓN
/ INSTITUTION: - Respiratory Medicine, Kingston Hospital
NHS Trust, Galsworthy Rd, Kingston Upon Thames, Surrey, UK, KT2 7QB.
RESUMEN
/ SUMMARY: - BACKGROUND: Immunosuppressive and
cytotoxic agents have been used as both an alternative to oral corticosteroids,
and as a means of maintaining a low dose of steroids in the treatment of
pulmonary sarcoidosis. OBJECTIVES: To determine the efficacy of
immunosuppressive and cytotoxic agents in the treatment of pulmonary
sarcoidosis. SEARCH STRATEGY: The Cochrane Airways Group trials register was
searched for possible randomised trials. Bibliographies were searched for other
potentially relevant trials. Searches were current as of February 2001.
SELECTION CRITERIA: Randomised controlled trials comparing an immunosuppressive
or cytotoxic therapy with a control in patients with pulmonary sarcoidosis were
included in the review. DATA COLLECTION AND ANALYSIS: Two reviewers
independently extracted data for entry in to the Review Manager statistical
package (MetaView 4.1). Pharmaceutical companies and study investigators were
contacted for unpublished trials. MAIN RESULTS: Four studies were included in
the review. Trials comparing methotrexate, chloroquine and cyclosporin A were
identified. No data could be combined for a meta-analysis. Data on lung
function, chest x-ray scores and dyspnoea were largely inconclusive. Adverse
effects were associated with methotrexate, cyclosporin A and chloroquine. In
one small study, methotrexate was associated with a steroid sparing effect
after 12 months of therapy, but no difference was observed at 6 months.
REVIEWER’S CONCLUSIONS: The current body of evidence supporting the use of
immunosuppressive agents and cytotoxic therapies is limited. Side-effects
associated with some of the therapies were severe. N. Ref:: 46
----------------------------------------------------
[18]
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
----------------------------------------------------
[19]
TÍTULO / TITLE: - The transplantation of
hematopoietic stem cells after non-myeloablative conditioning: a cellular
therapeutic approach to hematologic and genetic diseases.
REVISTA
/ JOURNAL: - Immunol Res 2003;28(1):13-24.
AUTORES
/ AUTHORS: - Maris M; Storb R
INSTITUCIÓN
/ INSTITUTION: - Fred Hutchinson Cancer Research Center,
and University of Washington, Seattle, WA, USA. mmaris@fhcrc.org
RESUMEN
/ SUMMARY: - Originally, allogeneic hematopoietic stem
cell transplantation (HSCT) was viewed as a form of rescue from the marrow
lethal effects of high doses of chemo-radiotherapy used to both eradicate malignancy
and to provide sufficient immunosuppression to ensure allogeneic engraftment.
Clear evidence of a therapeutic graft-versus-tumor (GVT) effect mediated by
allogeneic effector cells (T cells) has prompted the exploration of HSCT
regimens that rely solely upon host immunosuppression (non-myeloablative) to
facilitate allogeneic donor engraftment. The engrafted donor effector cells are
then used to accomplish the task of eradicating host malignant cells. The
non-myeloblative regimen developed in Seattle uses 2 Gy total body irradiation
(TBI) before transplant followed by postgrafting cyclosporine (CSP) and
mycophenolate mofetil (MMF). This regimen resulted in initial mixed donor-host
chimerism in all patients with hematologic malignancies and genetic disorders
who received HLA-matched sibling allografts. The 17% incidence of graft
rejection was reduced to 3% with the addition of fludarabine, 30 mg/m2/day on d
-4, -3, and -2. The non-myeloablative combination of fludarabine/TBI has also
been successful at achieving high engraftment rates in recipients of 10 of 10
HLA antigen matched unrelated donor HSCTs in patients with hematologic
malignancies. By reducing acute toxicities relative to conventional HSCT, most
patients have received their pre- and post-HSCT therapy almost exclusively as
outpatients. Acute and chronic GVHD occur after non-myeloablative HSCT, but the
incidence and severity appear less compared to conventional HSCT. As in
conventional transplants, immune dysregulation from GVHD and its treatment and
delayed reconstitution of immune function continue to present risks to patients
who have otherwise undergone successful non-myeloablative HSCT. Cellular
therapeutic effects have been observed after non-myeloablative HSCT such as
correction of inherited genetic disorders, and eradication of hematologic
malignant diseases and renal cell carcinoma via GVT responses. N. Ref:: 52
----------------------------------------------------
[20]
TÍTULO / TITLE: - Immunosuppressive
agents in childhood nephrotic syndrome: a meta-analysis of randomized
controlled trials.
REVISTA
/ JOURNAL: - Kidney Int 2001 May;59(5):1919-27.
AUTORES
/ AUTHORS: - Durkan AM; Hodson EM; Willis NS; Craig JC
INSTITUCIÓN
/ INSTITUTION: - Centre for Kidney Research, The Children’s
Hospital at Westmead, New South Wales, Australia.
RESUMEN
/ SUMMARY: - BACKGROUND: Many children with
steroid-sensitive nephrotic syndrome (SSNS) relapse frequently and receive
immunosuppressive agents. In this systematic review of randomized controlled
trials (RCTs), the benefits and harms of these immunosuppressive agents are
evaluated. METHODS: RCTs with outcome data at six months or more that evaluated
noncorticosteroid agents in relapsing SSNS were included. A summary relative
risk for relapse at 6 to 12 months was calculated using a random effects model.
RESULTS: Seventeen trials involving 631 children were identified.
Cyclophosphamide [3 trials; relative risk (RR) 0.44, 95% confidence interval
(CI), 0.26 to 0.73] and chlorambucil (2 trials; RR 0.13, 95% CI, 0.03 to 0.57)
significantly reduced the relapse risk at 6 to 12 months compared with
prednisone alone. In the single chlorambucil versus cyclophosphamide trial,
there was no observed difference in relapse risk at two years (RR 1.31, 95% CI,
0.80 to 2.13). Cyclosporine was as effective as cyclophosphamide (1 trial; RR
1.07, 95% CI, 0.48 to 2.35) and chlorambucil (1 trial; RR 0.82, 95% CI, 0.44 to
1.53), but the effect was not sustained when cyclosporine was ceased. During
treatment, levamisole (3 trials; RR 0.60, 95% CI, 0.45 to 0.79) was more
effective than steroids alone, but the effect was not sustained. CONCLUSIONS:
Cyclophosphamide, chorambucil, cyclosporine, and levamisole reduce the risk of
relapse in children with relapsing SSNS compared with prednisone alone.
Clinically important differences in efficacy among these agents are possible,
and further comparative trials are still needed. Meanwhile, the choice between
these agents depends on physician and patient preferences related to therapy
duration and complication type and frequency.
----------------------------------------------------
[21]
TÍTULO / TITLE: - “Stepping-up” from
methotrexate: a systematic review of randomised placebo controlled trials in
patients with rheumatoid arthritis with an incomplete response to methotrexate.
REVISTA
/ JOURNAL: - Ann Rheum Dis 2001 Nov;60 Suppl 3:iii51-4.
AUTORES
/ AUTHORS: - Hochberg MC; Tracy JK; Flores RH
INSTITUCIÓN
/ INSTITUTION: - Department of Medicine, University of
Maryland School of Medicine, Baltimore 21201, USA. N. Ref:: 20
----------------------------------------------------
[22]
TÍTULO / TITLE: - Drug immunosuppression
therapy for adult heart transplantation. Part 2: clinical applications and
results.
REVISTA
/ JOURNAL: - Ann Thorac Surg 2004 Jan;77(1):363-71.
AUTORES
/ AUTHORS: - Mueller XM
INSTITUCIÓN
/ INSTITUTION: - Department of Cardiovascular Surgery,
Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada. xavier.mueller@usherbrooke.ca
RESUMEN
/ SUMMARY: - This review describes the clinical
application of classical immunosuppressive drugs as well as that of more recent
drugs. All current immunosuppressive drugs target T-cell activation, and
cytokine production and clonal expansion, or both. Immunosuppressive protocols
can be broadly divided into induction therapy, maintenance immunosuppression,
and treatment of acute rejection episodes.
N. Ref:: 82
----------------------------------------------------
[23]
TÍTULO / TITLE: - Treatment of idiopathic
nephrosis by immunophillin modulation.
REVISTA
/ JOURNAL: - Nephrol Dial Transplant. Acceso gratuito
al texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://ndt.oupjournals.org/
●●
Cita: Nephrology Dialysis Transplantation: <> 2003 Aug;18 Suppl
6:vi79-86.
AUTORES
/ AUTHORS: - Meyrier A
INSTITUCIÓN
/ INSTITUTION: - Service de Nephrologie, Hopital Europeen
Georges Pompidou, 20 rue Leblanc, F-75015 Paris, France. alain.meyrier@brs.ap-hop-paris.fr
RESUMEN
/ SUMMARY: - Until 1985, glucocorticoids and cytotoxic
drugs were the only treatments available for idiopathic nephrotic syndrome
(nephrosis), that is, minimal change disease (MCD) and focal segmental
glomerulosclerosis (FSGS). Trials of cyclosporine (CsA) treatment of nephrosis,
the rationale of which was based on pathophysiologic considerations, have shown
that this immunophillin modulator is effective in inducing and maintaining
remission in patients suffering from idiopathic nephrotic syndrome. It appears
that the best results, in the order of 80% remission rate, are obtained in
steroid-sensitive cases, essentially MCD, and that in steroid-resistant FSGS
the drug obtains remission in no more than 20% of the cases. Addition of
glucocorticoids increases the success rate to approximately 30% of cases. Renal
toxicity is proportional to previous impairment of renal function, primary
renal disease (FSGS vs MCD) dosage >5.5 mg/kg/day and duration of treatment.
The better bioavailability of the new formulation of CsA (Neoral), implies that
the former dosage recommendations be reconsidered for distinctly lower figures.
Repeat renal biopsy after 1 year of continuous CsA treatment is advisable, as
stable serum creatinine levels may be falsely reassuring. CsA dependency is the
rule during the first year of treatment. However, in some 25% of cases stable
remission may be maintained after slow tapering off following 3-4 years of
treatment. Other immunophillin modulators have been tried in the treatment of
idiopathic nephrotic syndrome. Despite few preliminary reports indicating some
success of tacrolimus the effects of this drug do not seem convincingly
superior to CsA in terms of remission rate, toxicity and dependency. Rapamycin
has not been tried in the treatment of nephrosis. Anecdotal cases of de novo
FSGS induced by rapamycin in transplanted patients might indicate that this
drug is in fact contraindicated in the treatment of nephrosis. N. Ref:: 36
----------------------------------------------------
[24]
TÍTULO / TITLE: - In vitro generation of
IL-10-producing regulatory CD4+ T cells is induced by immunosuppressive drugs
and inhibited by Th1- and Th2-inducing cytokines.
REVISTA
/ JOURNAL: - Immunol Lett 2003 Jan 22;85(2):135-9.
AUTORES
/ AUTHORS: - O’Garra A; Barrat FJ
INSTITUCIÓN
/ INSTITUTION: - Division of Immunoregulation, The National
Institute for Medical Research (NIMR), The Ridgeway, Mill Hill, NW7 1AA,
London, UK. N. Ref:: 40
----------------------------------------------------
[25]
TÍTULO / TITLE: - Risk for myopathy with
statin therapy in high-risk patients.
REVISTA
/ JOURNAL: - Arch Intern Med 2003 Mar 10;163(5):553-64.
AUTORES
/ AUTHORS: - Ballantyne CM; Corsini A; Davidson MH;
Holdaas H; Jacobson TA; Leitersdorf E; Marz W; Reckless JP; Stein EA
INSTITUCIÓN
/ INSTITUTION: - Center for Cardiovascular Disease
Prevention, Baylor College of Medicine, 6565 Fannin, Mail Station A601, Suite
A656, Houston, TX 77030, USA. cmb@bcm.tmc.edu
RESUMEN
/ SUMMARY: - Emerging data suggest that the
3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins)
offer important benefits for the large population of individuals at high risk
for coronary heart disease. This population encompasses a sizable portion of
individuals who are also at high risk for drug-drug interactions due to their
need for multiple medications. In general, statins are associated with a very
small risk for myopathy (which may progress to fatal or nonfatal
rhabdomyolysis); however, the potential for drug-drug interactions is known to
increase this risk in specific high-risk groups. The incidence of myopathy
associated with statin therapy is dose related and is increased when statins
are used in combination with agents that share common metabolic pathways. Of
particular concern is the potential for interactions with other lipid-lowering
agents such as fibrates and niacin (nicotinic acid), which may be used in
patients with mixed lipidemia, and with immunosuppressive agents, such as
cyclosporine, which are commonly used in patients after transplantation.
Clinicians should be alert to the potential for drug-drug interactions to
minimize the risk of myopathy during long-term statin therapy in patients at
high risk for coronary heart disease. N.
Ref:: 128
----------------------------------------------------
[26]
TÍTULO / TITLE: - Renal transplantation:
can we reduce calcineurin inhibitor/stop steroids? Evidence based on protocol
biopsy findings.
REVISTA
/ JOURNAL: - J Am Soc Nephrol. Acceso gratuito al texto
completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.jasn.org/
●●
Cita: Journal of the American Society of Nephrology: <> 2003
Mar;14(3):755-66.
AUTORES
/ AUTHORS: - Gotti E; Perico N; Perna A; Gaspari F;
Cattaneo D; Caruso R; Ferrari S; Stucchi N; Marchetti G; Abbate M; Remuzzi G
INSTITUCIÓN
/ INSTITUTION: - Department of Medicine and
Transplantation, Ospedali Riuniti di Bergamo, Mario Negri Institute for
Pharmacological Research, Italy.
RESUMEN
/ SUMMARY: - How to combine antirejection drugs and which
is the optimal dose of steroids and calcineurin inhibitors beyond the first
year after kidney transplantation to maintain adequate immunosuppression
without major side effects are far from clear. Kidney transplant patients on
steroid, cyclosporine (CsA), and azathioprine were randomized to per-protocol
biopsy (n = 30) or no-biopsy (n = 29) 1 to 2 yr posttransplant. Steroid or CsA
were discontinued or reduced on the basis of biopsy to establish effects on
drug-related complications, acute rejection, and graft function over 3 yr of
follow-up. Serum creatinine, GFR (plasma clearance of iohexol), RPF (renal
clearance of p-aminohippurate), CsA pharmacokinetics, and adverse events were
monitored yearly. At the end, patients underwent a second biopsy. Per-protocol
biopsy histology revealed no lesions (n = 5, steroid withdrawal), CsA
nephropathy (n = 13, CsA discontinuation/reduction), or chronic rejection (n =
12, standard therapy). Reducing the drug regimen led to overall fewer side
effects related to immunosuppression as compared with standard therapy or
no-biopsy. Steroids were safely stopped with no acute rejection or graft loss.
Complete CsA discontinuation was associated with acute rejection in the first
four patients. Lowering CsA to low target CsA trough (30 to 70 ng/ml) never led
to acute rejection or major renal function deterioration. Biopsy patients on
conventional regimen had no acute rejection, one graft loss, no significant
change in GFR, and significant RPF decline. No-biopsy controls: no acute rejection,
one graft loss, significant decline of GFR and RPF. By serial biopsy analysis,
severe lesions did not develop in patients with steroid discontinuation in
contrast to patients on standard therapy over follow-up. CsA reduction did not
adversely affect histology. Per-protocol biopsy more than 1 yr after kidney
transplantation is a safe procedure to guide change of drug regimen and to
lower the risk of major side effects.
----------------------------------------------------
[27]
TÍTULO / TITLE: - Drug immunosuppression
therapy for adult heart transplantation. Part 1: immune response to allograft
and mechanism of action of immunosuppressants.
REVISTA
/ JOURNAL: - Ann Thorac Surg 2004 Jan;77(1):354-62.
AUTORES
/ AUTHORS: - Mueller XM
INSTITUCIÓN
/ INSTITUTION: - Department of Cardiovascular Surgery,
Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada. xavier.mueller@usherbrooke.ca
RESUMEN
/ SUMMARY: - In the early days of transplantation,
immunosuppression therapy was rather broad and nonspecific, mainly using
high-dose corticosteroids and azathioprine. Thereafter we progressively
narrowed the target of immunosuppressive strategy starting with polyclonal
antibodies. The introduction of cyclosporine, OKT3, and tacrolimus further
narrowed the target on the T-cell pathways. More recently mycophenolate mofetil
progressively took the place of azathioprine with its higher lymphocyte
specificity and sirolimus and interleukin-2 receptor antibodies were
introduced. In this field in constant movement the aim is to find a drug or a
regimen that provides optimal immunosuppression therapy with minimal side
effects, in other words to find the right balance between overimmunosuppression
and underimmunosuppression therapy. This review is divided into two parts. The
first part will provide a basic understanding of the immunologic response to
allograft and explain how conventional and recently introduced
immunosuppressive agents work. The second part will describe the clinical
application of immunosuppressive drugs to provide practical information for
those in charge of heart transplant recipients. N. Ref:: 68
----------------------------------------------------
[28]
TÍTULO / TITLE: - Longstanding
obliterative panarteritis in Kawasaki disease: lack of cyclosporin A effect.
REVISTA
/ JOURNAL: - Pediatrics 2003 Oct;112(4):986-92.
AUTORES
/ AUTHORS: - Kuijpers TW; Biezeveld M; Achterhuis A;
Kuipers I; Lam J; Hack CE; Becker AE; van der Wal AC
INSTITUCIÓN
/ INSTITUTION: - Emma Children’s Hospital, Academic Medical
Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. t.w.kuijpers@amc.uva.nl
RESUMEN
/ SUMMARY: - Kawasaki disease is a childhood vasculitis
of medium-sized vessels, affecting the coronary arteries in particular. We have
treated a therapy-resistant child who met all diagnostic criteria for Kawasaki
disease. After the boy was given intravenous immunoglobulins and salicylates,
as well as several courses of pulsed methylprednisolone, disease recurred and
coronary artery lesions became progressively detectable. Cyclosporin A was
started and seemed clinically effective. In contrast to the positive effect on
inflammatory parameters, ie, C-reactive protein and white blood cell counts, a
novel plasma marker for cytotoxicity (granzyme B) remained elevated. Coronary
disease progressed to fatal obstruction and myocardial infarction.
Echocardiography, electrocardiograms, and myocardial creatine phosphokinase did
not predict impending death. At autopsy an obliterative panarteritis was
observed resulting from massive fibrointimal proliferation, affecting the aorta
and several large and medium-sized arteries. Immunophenotypic analysis of the
inflammatory infiltrates in arteries revealed mainly granzyme-positive
cytotoxic T cells and macrophages in the intima and media, as well as nodular
aggregates of T cells, B cells, and plasma cells in the adventitia of affected
arteries. These findings further endorse the role of specific cellular and
humoral immunity in Kawasaki disease. Unremitting coronary arteritis and
excessive smooth muscle hyperplasia resulted in coronary occlusion despite the
use of cyclosporin A. N.
Ref:: 37
----------------------------------------------------
[29]
TÍTULO / TITLE: - Mammalian target of
rapamycin inhibition as therapy for hematologic malignancies.
REVISTA
/ JOURNAL: - Cancer 2004 Feb 15;100(4):657-66.
●●
Enlace al texto completo (gratuito o de pago) 1002/cncr.20026
AUTORES
/ AUTHORS: - Panwalkar A; Verstovsek S; Giles FJ
INSTITUCIÓN
/ INSTITUTION: - Section of Developmental Therapeutics,
Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston,
Texas, USA.
RESUMEN
/ SUMMARY: - The mammalian target of rapamycin (mTOR)
is a downstream effector of the phosphatidylinositol 3-kinase (PI3K)/Akt
(protein kinase B) signaling pathway, which mediates cell survival and
proliferation. mTOR regulates essential signal-transduction pathways, is
involved in the coupling of growth stimuli with cell cycle progression, and
initiates mRNA translation in response to favorable nutrient environments. mTOR
is involved in regulating many aspects of cell growth, including membrane
traffic, protein degradation, protein kinase C signaling, ribosome biogenesis,
and transcription. Because mTOR activates both the 40S ribosomal protein S6
kinase (p70s6k) and the eukaryotic initiation factor 4E-binding protein 1, its
inhibitors cause G1-phase cell cycle arrest. Inhibitors of mTOR also prevent
cyclin dependent kinase (CDK) activation, inhibit retinoblastoma protein
phosphorylation, and accelerate the turnover of cyclin D1, leading to a
deficiency of active CDK4/cyclin D1 complexes, all of which may help cause
G1-phase arrest. It is known that the phosphatase and tensin homologue tumor
suppressor gene (PTEN) plays a major role in embryonic development, cell
migration, and apoptosis. Malignancies with PTEN mutations, which are associated
with constitutive activation of the PI3K/Akt pathway, are relatively resistant
to apoptosis and may be particularly sensitive to mTOR inhibitors. Rapamycin
analogs with relatively favorable pharmaceutical properties, including CCI-779,
RAD001, and AP23573, are under investigation in patients with hematologic
malignancies. N.
Ref:: 116
----------------------------------------------------
[30]
TÍTULO / TITLE: - Cholesteryl ester
transfer protein facilitates the movement of water-insoluble drugs between
lipoproteins: a novel biological function for a well-characterized lipid
transfer protein.
REVISTA
/ JOURNAL: - Biochem Pharmacol 2002 Dec
15;64(12):1669-75.
AUTORES
/ AUTHORS: - Kwong M; Wasan KM
INSTITUCIÓN
/ INSTITUTION: - Division of Pharmaceutics and
Biopharmaceutics, Faculty of Pharmaceutical Sciences, The University of British
Columbia, 2146 East Mall Avenue, Vancouver, BC, Canada V6T 1Z3.
RESUMEN
/ SUMMARY: - This review article addresses the recently
discovered finding that cholesteryl ester transfer protein (CETP) can
facilitate the transfer of water-insoluble drugs between different lipoprotein
subclasses. This protein, which is often referred to as lipid transfer protein
I (LTP I), is involved in the lipid regulation of lipoproteins. It is
responsible for the facilitated transfer of core lipoprotein lipids,
cholesteryl ester and triglycerides, and approximately one-third of the coat
lipoprotein lipid, phosphatidylcholine, between different plasma lipoproteins.
The human body appears to recognize exogenous water-insoluble drugs as
lipid-like particles, which suggests that these compounds may interact with
lipoproteins just like endogenous plasma lipids, and thus their transfer
between lipoproteins may be facilitated by plasma CETP. Patients with a variety
of diseases (i.e. diabetes, cancer, AIDS) often exhibit hypo- and/or
hypercholesterolemia and triglyceridemia, commonly referred to as
dyslipidemias, which result in changes in their plasma lipoprotein-lipid
composition and concentration. The interaction of water-insoluble drugs with
these dyslipidemic lipoproteins may be responsible for the differences seen in
the pharmacokinetics and pharmacodynamics of the drug within different diseased
patient populations. It is possible that these differences may be linked to the
ability of CETP to transfer these compounds from one lipoprotein to another.
This review examines the current understanding of the relationship between CETP
activity and the lipoprotein distribution of a number of compounds (e.g.
amphotericin B and cyclosporine A). It further suggests that additional
research will expand our understanding of the role of CETP to explain other
functions in lipophilic drug distribution and metabolism. N. Ref:: 45
----------------------------------------------------
[31]
TÍTULO / TITLE: - Advances in
transplantation tolerance.
REVISTA
/ JOURNAL: - Lancet 2001 Jun 16;357(9272):1959-63.
AUTORES
/ AUTHORS: - Yu X; Carpenter P; Anasetti C
INSTITUCIÓN
/ INSTITUTION: - Human Immunogenetics Program, Fred
Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
RESUMEN
/ SUMMARY: - Immunosuppressive drugs developed in the
past two decades have improved the short-term survival of organ allografts, but
tolerance has not been achieved and almost all transplant recipients continue
to require drugs throughout life. Graft rejection arises from the cognate
interaction of T cells with antigen-presenting cells, the recognition of
alloantigen through the T-cell receptor, and the delivery of accessory stimulation
signals. Once activated by the specific antigen, replicating T cells die if
they are re-exposed to the same antigen. Since depletion of antigen-activated T
cells is one critical mechanism of transplantation tolerance, drugs such as
ciclosporin that interfere with activation-induced T-cell death could inhibit
tolerance, whereas drugs such as mycophenolate mofetil, that induce the death
of activated T cells, could facilitate tolerance. Other tolerance mechanisms
depend on inactivation rather than elimination of allograft reactive T cells.
When antigen recognition occurs without costimulation through the CD28 and
CD154 accessory receptors, or in absence of cell division, T cells become
unresponsive. Thus, inhibitors of CD28 and CD154, and inhibition of T-cell
division by rapamycin promotes transplantation tolerance. N. Ref:: 54
----------------------------------------------------
[32]
TÍTULO / TITLE: - Rational use of new and
existing disease-modifying agents in rheumatoid arthritis.
REVISTA
/ JOURNAL: - Ann Intern Med. Acceso gratuito al texto
completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.annals.org/
●●
Cita: Annals of Internal Medicine: <> 2001 Apr 17;134(8):695-706.
AUTORES
/ AUTHORS: - Kremer JM
INSTITUCIÓN
/ INSTITUTION: - The Center for Rheumatology, Albany, New
York, USA. jkremer@rheum-docs.com
RESUMEN
/ SUMMARY: - Because of radiographic evidence of progressive
bone loss and the inability to eliminate synovial proliferation with
methotrexate, it became apparent that therapy for rheumatoid arthritis needed
further advancement. Methotrexate is not a remission-inducing drug and may have
dose-limiting toxicity. In the past 2 years, three new disease-modifying
antirheumatic drugs (DMARDs) have been approved: leflunomide, etanercept, and
infliximab. Each of these agents has demonstrated efficacy compared with
placebo in randomized, controlled studies. Because methotrexate had a dominant
therapeutic role, the new drugs were also studied in combination with it. Other
established DMARDs, such as sulfasalazine and hydroxychloroquine, have also
demonstrated efficacy when used together with methotrexate. The results of
these combination studies clearly demonstrate that clinical responses can be
meaningfully improved when new and existing DMARDs are added to methotrexate.
Although toxicity remains a serious concern when powerful immune modulators and
antimetabolites are used in combination, relatively few serious adverse events
have been reported during 2-year treatment periods. It has also become apparent
that combinations of new DMARDs and methotrexate virtually halt radiographic
progression over 2 years. The new agents are expensive, but annual costs must
be weighed against the personal and societal expense of joint arthroplasty,
hospitalizations, disability, and diminished quality of life that accompanies
poorly controlled rheumatoid arthritis. The ultimate value of combination DMARD
therapy with methotrexate will be determined by long-term data on safety,
efficacy, and effects on radiographic deterioration of bone. Additional
long-term observational data on the incidence of joint arthroplasty and
disability will help to place the issue of societal costs in a better
perspective. This will allow the value of aggressive treatment to be
established with certainty. N.
Ref:: 87
----------------------------------------------------
[33]
TÍTULO / TITLE: - Clinical development of
mammalian target of rapamycin inhibitors.
REVISTA
/ JOURNAL: - Hematol Oncol Clin North Am 2002
Oct;16(5):1101-14.
AUTORES
/ AUTHORS: - Dancey JE
INSTITUCIÓN
/ INSTITUTION: - Cancer Treatment Evaluation Program,
Division of Cancer Treatment and Diagnosis, Investigational Drug
Branch/CTEP/DCTD/NCI, 6130 Executive Boulevard, EPN 7131, Rockville, MD 20854,
USA. danceyj@ctep.nci.nih.gov
RESUMEN
/ SUMMARY: - Rapamycin and CCI-779 have significant in
vitro and in vivo anti-proliferative activity against a broad range of human
tumor cell lines, justifying the clinical evaluation of this class of agent in
cancer patients. Preliminary results from phase I studies of CCI-779 suggest
that the agent is well tolerated and has anti-tumor activity. The challenge to
investigators is to efficiently determine what role this class of agent will
play in the treatment of cancer patients.
N. Ref:: 69
----------------------------------------------------
[34]
TÍTULO / TITLE: - Review article: medical
treatment of mild to moderately active Crohn’s disease.
REVISTA
/ JOURNAL: - Aliment Pharmacol Ther 2003 Jun;17 Suppl
2:18-22.
AUTORES
/ AUTHORS: - Lofberg R
INSTITUCIÓN
/ INSTITUTION: - Karolinska Institutet, IBD-unit at HMQ
Sophia Hospital, Stockholm, Sweden. ibd@sophiahemmet.se
RESUMEN
/ SUMMARY: - Crohn’s disease is a chronic, debilitating
subset of inflammatory bowel diseases, which may affect any part of the
gastrointestinal tract. The most common sites of inflammation are the terminal
ileum and/or the colon. Fistulous disease is present in up to 20% of patients,
particularly in those having rectal involvement. The aetiology of Crohn’s
disease still remains obscure, therefore medical therapy is directed towards
symptomatic relief in active disease and relapse prevention in the long-term
setting. Contemporary Crohn’s disease management comprises individual treatment
depending mainly on Crohn’s disease localization in the gastrointestinal tract
and the disease severity. The mainstay of current medical treatment for mild to
moderately active stages of Crohn’s disease includes aminosalicylates,
antibiotics, glucococorticosteroids and immunomodulators. Biologics such as
anti TNF-compounds and anti-integrins are being introduced. N. Ref:: 21
----------------------------------------------------
[35]
TÍTULO / TITLE: - Treatment of nephrotic
syndrome in children and controlled trials.
REVISTA
/ JOURNAL: - Nephrol Dial Transplant. Acceso gratuito
al texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://ndt.oupjournals.org/
●●
Cita: Nephrology Dialysis Transplantation: <> 2003 Aug;18 Suppl 6:vi75-8.
AUTORES
/ AUTHORS: - Filler G
INSTITUCIÓN
/ INSTITUTION: - Department of Paediatrics, Division of
Nephrology, Children’s Hospital of Eastern Ontario, University of Ottawa,
Canada. filler@cheo.on.ca
RESUMEN
/ SUMMARY: - AIM: To determine the sequential therapy
of childhood nephrotic syndrome (NS) with presumed minimal change nephropathy
using the evidence from clinical trials. METHODS: Meta-analysis of 22
randomized controlled trials was performed, using frequency of relapse and side
effects of therapeutic regimes. RESULTS: A meta-analysis of seven trials
comparing duration of therapy for initial onset showed that duration of at
least 3 months significantly reduced the risk of relapse at 12-24 months
(relative risk 0.73; 95% confidence interval 0.60-0.89) without an increase in adverse
events. Five trials were performed for steroid treatment of relapse.
Deflazacort reduced relapses during therapy, but is not generally available. No
difference was observed when comparing single and divided dosing of prednisone.
Frequency of relapses could not be influenced by duration of relapse therapy.
Alternate day therapy was more effective than intermittent use of prednisone.
Two studies out of five on cyclophosphamide or chlorambucil showed consistently
that alkylating agents should be used before cyclosporine as alternative
therapy to steroids. CONCLUSIONS: Children with initial onset of NS should be
treated with prednisone at a dose of 60 mg/m(2)/day for 6 weeks, followed by a
dose of 40 mg/m(2)/48 h for at least another 6 weeks. If steroid toxicity for
treatment of relapsing NS requires alternative treatment, cyclophosphamide (2
mg/kg/day for at least 8 weeks) remains the drug of choice with a curative
potential. If children still relapse after alkylating agents, levamisole may
serve as an alternative only for frequent relapsing NS, whereas
steroid-dependent NS should be treated with cyclosporine.
----------------------------------------------------
[36]
TÍTULO / TITLE: - Non-corticosteroid
treatment for nephrotic syndrome in children.
REVISTA
/ JOURNAL: - Cochrane Database Syst Rev
2001;(4):CD002290.
AUTORES
/ AUTHORS: - Durkan A; Hodson E; Willis N; Craig J
INSTITUCIÓN
/ INSTITUTION: - Centre for Kidney Research, The Children’s
Hospital at Westmead, Locked Bag 4001, Westmead, NSW, Australia, 2145. ElisaH@chw.edu.au
RESUMEN
/ SUMMARY: - BACKGROUND: Eighty to ninety per cent
children with steroid sensitive nephrotic syndrome (SSNS) have one or more
relapses. About half of these children relapse frequently and are at risk of
the adverse effects of corticosteroids. Non-corticosteroid immunosuppressive
agents are used to prolong periods of remission in children, who relapse
frequently. However these non-corticosteroid agents also have significant potential
adverse effects. Currently there is no consensus as to the most appropriate
second line agent in children who are steroid sensitive, but who continue to
relapse. In this systematic review of randomised controlled trials (RCTs), the
benefits and harms of these immunosuppressive agents are evaluated. OBJECTIVES:
To evaluate the benefits and harms of non-corticosteroid immunosuppressive
agents in relapsing SSNS in children. SEARCH STRATEGY: Published and
unpublished randomised controlled trials were identified from the Cochrane
Controlled Trials Register, MEDLINE, EMBASE, reference lists of articles,
abstracts from proceedings and contact with known investigators in the area.
SELECTION CRITERIA: Randomised or quasi-randomised trials were included if they
were carried out in children (aged three months to 18 years) with relapsing
SSNS, if they compared non-corticosteroid agents with placebo, prednisone or no
treatment, different doses and/ or durations of the same non-corticosteroid
agent, different non-corticosteroid agents and if they had outcome data at six
months or more. DATA COLLECTION AND ANALYSIS: Two reviewers independently
reviewed all eligible studies for inclusion, assessed study quality and
extracted data. The principle outcome measure was the number of children with
and without relapse after six and 12 to 24 months. Secondary outcomes sought
were the mean time to next relapse, the mean number of relapses per year and
adverse events. A random effects model was used to estimate summary effect measures
after testing for heterogeneity. Examination of possible between-study
differences due to study quality, different interventions and different
populations was attempted by subgroup analysis. MAIN RESULTS: Eighteen trials
involving 828 children were identified. Cyclophosphamide (three trials;
relative risk (RR) 0.44; 95% confidence intervals (95% CI) 0.26 to 0.73) and
chlorambucil (two trials; RR 0.13; 95% CI 0.03 to 0.57) significantly reduced
the relapse risk at six to twelve months compared with prednisone alone. In the
single chlorambucil versus cyclophosphamide trial, there was no observed
difference in relapse risk at two years (RR 1.31; 95% CI 0.80 to 2.13).
Cyclosporin was as effective as cyclophosphamide (one trial, RR 1.07; 95% CI
0.48 to 2.35) and chlorambucil (one trial, RR 0.82; 95% CI 0.44 to 1.53) but
the effect was not sustained when cyclosporin was ceased. During treatment
levamisole (three trials, RR 0.60; 95% CI 0.45 to 0.79) was more effective than
steroids alone but the effect was not sustained. Mizoribine (one trial) and
azathioprine (two trials) were no more effective than placebo or prednisone
alone in maintaining remission. REVIEWER’S CONCLUSIONS: Eight weeks courses of
cyclophosphamide or chorambucil and prolonged courses of cyclosporin and
levamisole reduce the risk of relapse in children with relapsing SSNS compared
with corticosteroids alone. Clinically important differences in efficacy among
these agents are possible and further comparative trials are still needed.
Meanwhile choice between these agents depends on physician and patient
preferences related to therapy duration and the type and frequency of
complications. N.
Ref:: 49
----------------------------------------------------
[37]
TÍTULO / TITLE: - Cytotoxic drugs and interferons
for chronic inflammatory demyelinating polyradiculoneuropathy.
REVISTA
/ JOURNAL: - Cochrane Database Syst Rev
2003;(1):CD003280.
AUTORES
/ AUTHORS: - Hughes RA; Swan AV; van Doorn PA
INSTITUCIÓN
/ INSTITUTION: - Department of Neuroimmunology, Guy’s,
King’s and St Thomas’ School of Medicine, 2nd Floor Hodgkin
Building, Guy’s Hospital, London, UK, SE1 1UL. richard.a.hughes@kcl.ac.uk
RESUMEN
/ SUMMARY: - BACKGROUND: Chronic inflammatory demyelinating
polyradiculoneuropathy is a disease causing progressive or relapsing and
remitting weakness and numbness. It is probably due to an autoimmune
inflammatory process. Immunosuppressive or immunomodulatory drugs would be
expected to be beneficial. OBJECTIVES: We aimed to review systematically the
evidence from randomised trials concerning cytotoxic drugs and interferons for
chronic inflammatory demyelinating polyradiculoneuropathy. SEARCH STRATEGY: We
searched the Cochrane Neuromuscular Disease Group trials register (searched
December 2001), MEDLINE (searched January 1977 to December 2001), EMBASE
(January 1980 to December 2001), CINAHL (searched January 1982 to December
2001) and LILACS (searched January 1982 to December 2001). We contacted the
authors of the trials identified and other disease experts seeking other
published and unpublished trials. SELECTION CRITERIA: We sought randomised and
quasi-randomised trials of all immunosuppressive agents such as azathioprine,
cyclophosphamide, methotrexate, cyclosporin A, mycophenolate mofetil, and
rituximab and all immunomodulatory agents such as alpha interferon and beta
interferon in participants fulfilling standard diagnostic criteria for chronic
inflammatory demyelinating polyradiculoneuropathy. DATA COLLECTION AND
ANALYSIS: Two of us independently selected the trials which met our criteria,
judged their methodological quality and extracted the data onto specially
designed forms. We wanted to measure the change in disability after one year as
our primary outcome measure. MAIN RESULTS: We found one parallel group open
trial of azathioprine for nine months involving 27 participants and another of
interferon beta involving 10 participants in a double blind crossover trial
with each treatment period lasting 12 weeks. Neither trial provided our primary
outcome measure and neither showed a significant beneficial effect on any of
the outcome measures selected by the authors or ourselves in the protocol for
this review. REVIEWER’S CONCLUSIONS: The evidence is inadequate to decide
whether azathioprine, interferon beta or any other immunosuppressive drug or
interferon is beneficial in chronic inflammatory demyelinating
polyradiculoneuropathy. N.
Ref:: 66
----------------------------------------------------
[38]
TÍTULO / TITLE: - Effects of
immunosuppressive drugs on dendritic cells and tolerance induction.
REVISTA
/ JOURNAL: - Transplantation 2003 May 15;75(9
Suppl):37S-42S.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000067950.90241.1D
AUTORES
/ AUTHORS: - Lagaraine C; Lebranchu Y
INSTITUCIÓN
/ INSTITUTION: - EA 3249, Cellules hematopoietiques,
hemostase et greffe, Laboratoire d’immunologie, Faculte de medecine, Tours,
France.
RESUMEN
/ SUMMARY: - Dendritic cells, the most effective
antigen-presenting cells for priming naive T cells and initiating immune
responses, are also able to induce tolerance. This balance between immunity and
tolerance depends on the functional stage of dendritic cells (DC). Activation
of naive T cells by immature DC can induce tolerance. It is therefore of
interest to summarize the effects of immunosuppressive agents on DC maturation
and functions. In contrast to glucocorticosteroids, mycophenolate mofetil, and
vitamin D(3) analogs, calcineurin inhibitors do not seem to inhibit DC
maturation in in vitro culture systems. However, these molecules all appear to
interfere with DC functions. N.
Ref:: 44
----------------------------------------------------
[39]
TÍTULO / TITLE: - Donor-specific
tolerance in fully major histocompatibility major histocompatibility
complex-mismatched limb allograft transplants under an anti-alphabeta T-cell
receptor monoclonal antibody and cyclosporine A protocol.
REVISTA
/ JOURNAL: - Transplantation 2003 Dec 27;76(12):1662-8.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000105343.49626.6F
AUTORES
/ AUTHORS: - Siemionow MZ; Izycki DM; Zielinski M
INSTITUCIÓN
/ INSTITUTION: - Department of Plastic Surgery, Cleveland
Clinic Foundation, A60, 9500 Euclid Avenue, Cleveland, OH 44195, USA. siemiom@ccf.org
RESUMEN
/ SUMMARY: - BACKGROUND: Recent studies have
demonstrated that treatment with alphabeta-T-cell receptor (TCR) monoclonal
antibody and cyclosporine A (CsA) can extend survival in composite tissue
allografts (CTA). The purpose of this study was to induce tolerance in fully
major histocompatibility complex (MHC)-mismatched rat limb allografts under 7
days of a combined alphabeta-TCR-CsA protocol. METHODS: The authors performed
30 hind-limb allotransplantations across the MHC barrier between Brown Norway
donors (BN; RT1n) and Lewis recipients (LEW; RT1l). Isograft and allograft
controls received no treatment. The experimental groups received monotherapy of
alphabeta-TCR and CsA or a combination of alphabeta-TCR and CsA for 7 days
only. Donor-specific tolerance and immunocompetence were determined by standard
skin grafting in vivo and mixed lymphocyte reaction (MLR) in vitro. The
efficacy of immunosuppressive therapy and the level of donor-specific chimerism
were determined by flow cytometry. RESULTS: Long-term survival (>350 days)
was achieved in allograft recipients (n=6) under the 7-day protocol of combined
alphabeta-TCR-CsA. Donor-specific tolerance and immunocompetence of long-term
chimeras were confirmed by acceptance of skin grafts from the donors and
rejection of the third-party alloantigens (AxC Irish). At day 120, MLR
demonstrated unresponsiveness to the host and donor antigens but strong
reactivity against third-party alloantigens. Flow cytometry confirmed the high
efficacy of immunosuppressive treatment and the development of donor-specific
chimerism (7.6% of CD4+-RT1n+ cells, 1.3% of CD8+-RT1n+ cells, and 16.5% of
CD45RA+-RT1n+ cells) in the periphery of tolerated recipients. CONCLUSIONS:
Combined therapy of alphabeta-TCR-CsA for 7 days resulted in tolerance
induction in fully MHC-mismatched rat hind-limb allografts. Tolerance was
directly associated with stable, donor-specific chimerism.
----------------------------------------------------
[40]
TÍTULO / TITLE: - Immunosuppressive
agents for treating IgA nephropathy.
REVISTA
/ JOURNAL: - Cochrane Database Syst Rev
2003;(4):CD003965.
●●
Enlace al texto completo (gratuito o de pago) 1002/14651858.CD003965
AUTORES
/ AUTHORS: - Samuels JA; Strippoli GF; Craig JC; Schena
FP; Molony DA
INSTITUCIÓN
/ INSTITUTION: - Nephrology / Pediatric Nephrology,
UT-Houston Health Science Center, 6431 Fannin Street, MSB 4-148, Houston, TX
77030, USA. Joshua.A.Samuels@uth.tmc.edu
RESUMEN
/ SUMMARY: - BACKGROUND: IgA nephropathy (IgAN) is a world-wide
disease and the cause of end-stage renal failure (ESRF) in 15 to 20% of
patients within 10 years and in 30 to 40% of individuals within 20 years from
the apparent onset of disease. No specific treatment has yet been established
but many approaches have been investigated. OBJECTIVES: To assess the benefits
and harms of immunosuppressive treatment for IgAN. SEARCH STRATEGY: We searched
The Cochrane Renal Group’s specialized register (May 2003), Cochrane Central
Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 3, 2002)
MEDLINE (1966 - September 2002), EMBASE (1988 - September 2002) and
handsearched reference lists of retrieved articles and conference proceedings.
SELECTION CRITERIA: Randomized controlled trials (RCTs) and quasi-RCTs
comparing treatment of IgAN with immunosuppressive agents against placebo, no
treatment, other immunosuppressive or non-immunosuppressive agents. DATA
COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and
extracted data. Statistical analyses were performed using the random effects
model and the results expressed as relative risk (RR) for dichotomous outcomes
and weighted mean difference (WMD) for continuous outcomes, with 95% confidence
intervals (CI). MAIN RESULTS: Thirteen eligible RCTs involving 623 patients
were identified. All identified RCTs had a placebo, no treatment or
warfarin/dipyridamole control group. Seven trials used steroids, three used
alkylating agents/cyclosporin and three used combinations of steroids and alkylating
agents/cyclosporin. No trial directly compared steroids versus alkylating
agents/cyclosporin. Quality was sub-optimal. Steroids were associated with a
lower risk of progression to ESRF (RR 0.44, 95% CI 0.25 to 0.80) and lower
urinary protein excretion (WMD -0.49 g/24h, 95% CI -0.72 to -0.12). Urinary
protein excretion was lower for patients treated with alkylating
agents/cyclosporin compared to placebo/no treatment (WMD -0.94 g/24h, 95% CI
-1.43 to -0.46). There was no significant reduction of urinary protein
excretion with combination treatment of steroids and alkylating agents compared
with placebo/no treatment. REVIEWER’S CONCLUSIONS: The optimal management of
IgAN remains uncertain. The RCTs identified were small, of sub-optimal
methodological quality and tended to only report favorable and surrogate
outcomes without a thorough reporting of treatment harms. All outcomes favor
the use of immunosuppressive interventions, with steroids appearing to be the
most promising. Further study, in the form of RCTs, is necessary to ascertain
which patients would benefit from these interventions, whether they are the
ones with early signs of renal dysfunction or those with more advanced renal
impairment. N. Ref:: 47
----------------------------------------------------
[41]
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.
----------------------------------------------------
[42]
TÍTULO / TITLE: - Dimerizer-regulated
gene expression.
REVISTA
/ JOURNAL: - Curr Opin Biotechnol 2002
Oct;13(5):459-67.
AUTORES
/ AUTHORS: - Pollock R; Clackson T
INSTITUCIÓN
/ INSTITUTION: - ARIAD Gene Therapeutics, 26 Landsdowne
Street, Cambridge, MA 02139, USA. roy.pollock@ariad.com
RESUMEN
/ SUMMARY: - Control of gene expression using small
molecules is a powerful research tool and has clinical utility in the context
of regulated gene therapy. Use of chemical inducers of dimerization, or
dimerizers, for this purpose has several advantages, including tight
regulation, modularity to facilitate iterative improvements, and assembly from
human proteins to minimize immune responses in clinical applications. Recent
developments include the use of the rapamycin-based dimerizer system to
regulate the expression of endogenous genes, the generation of new chemical
dimerizers based on FK506, dexamethasone and methotrexate, and progress towards
the clinical use of adeno-associated virus and adenovirus vectors regulated by
rapamycin analogs. N.
Ref:: 40
----------------------------------------------------
[43]
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
----------------------------------------------------
[44]
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
----------------------------------------------------
[45]
TÍTULO / TITLE: - The fission yeast TOR
proteins and the rapamycin response: an unexpected tale.
REVISTA
/ JOURNAL: - Curr Top Microbiol Immunol 2004;279:85-95.
AUTORES
/ AUTHORS: - Weisman R
INSTITUCIÓN
/ INSTITUTION: - Department of Molecular Microbiology and
Biotechnology, Faculty of Life Sciences, Tel-Aviv University, 69978 Tel-Aviv,
Israel. ronitt@post.tau.ac.il
RESUMEN
/ SUMMARY: - The TOR proteins are known as key
regulators of cell growth in response to nutritional and mitogenic signals and
as targets for the immunosuppressive and anti-cancerous drug rapamycin. The
fission yeast Schizosaccharomyces pombe has two TOR homologues, tor1+ and
tor2+. Despite their structural similarity, these genes have distinct
functions: tor1+ is required under starvation, extreme temperatures, and
osmotic or oxidative stress conditions, whereas tor2+ is required under normal
growth conditions. Surprisingly, rapamycin does not seem to inhibit the S.
pombe TOR-related functions. Rapamycin specifically inhibits sexual development
in S. pombe, and this seems to stem from direct inhibition of the S. pombe
FKBP12 homologue. Why S. pombe cells are resistant to rapamycin during the
growth phase is as yet unclear and awaits further analysis of the TOR-dependent
signaling pathways. N.
Ref:: 27
----------------------------------------------------
[46]
TÍTULO / TITLE: - Renal function as a
predictor of long-term graft survival in renal transplant patients.
REVISTA
/ JOURNAL: - Nephrol Dial Transplant. Acceso gratuito
al texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://ndt.oupjournals.org/
●●
Cita: Nephrology Dialysis Transplantation: <> 2003 May;18 Suppl 1:i3-6.
AUTORES
/ AUTHORS: - First MR
INSTITUCIÓN
/ INSTITUTION: - Research and Development, Fujisawa
Healthcare, Inc., Deerfield, IL 60015, USA. roy_first@fujisawa.com
RESUMEN
/ SUMMARY: - Acute rejection is a major risk factor for
kidney graft failure. However, as acute rejection has been progressively
reduced by recent immunosuppressive regimens, other risk factors are becoming
increasingly important. Evidence is accumulating that early renal function
predicts long-term outcome. A recent registry survey of more than 100 000 kidney
transplants found that 6- and 12-month serum creatinine levels, as well as the
change between 6 and 12 months, are strongly associated with long-term graft
survival. A survey of paediatric renal transplant recipients showed that poor
creatinine clearance (<50 ml/min) as early as 30 days post-transplant
predicted an annual rate of graft loss of 13% compared with <3% in patients
with 30-day clearance >50 ml/min. This association between early renal
function and long-term outcome was confirmed in multicentre studies. Renal
transplant recipients (n=572) with 6-month serum creatinine levels >1.5
mg/dl suffered 3-year graft loss of 19.3% compared with only 8.5% in patients
with levels <1.6 mg/dl (P<0.001). Significantly fewer patients receiving
tacrolimus had 12-month serum creatinine levels >1.5 mg/dl compared with
cyclosporin (42 versus 54%, P<0.05). Interestingly, a single-centre study
(n=436) found that while glomerular filtration rate (GFR) at 6 months
post-transplant had remained stable over the last decade, the rate of loss of
renal function had decreased. A lower rate of GFR loss was associated with
absence of rejection, use of mycophenolate mofetil rather than azathioprine and
use of tacrolimus rather than cyclosporin (P<0.01). In conclusion, early measures
of renal function allow identification of those patients at highest risk of
graft failure and provide an invaluable tool for improving outcomes by tailored
immunosuppression. The choice of such immunosuppression should be guided not
only by its ability to prevent rejection, but also by its impact on renal
function. N. Ref:: 11
----------------------------------------------------
[47]
TÍTULO / TITLE: - Immunosuppressive
treatment for multifocal motor neuropathy.
REVISTA
/ JOURNAL: - Cochrane Database Syst Rev
2002;(2):CD003217.
AUTORES
/ AUTHORS: - Umapathi T; Hughes RA; Nobile-Orazio E;
Leger JM
INSTITUCIÓN
/ INSTITUTION: - Department of Neurology, National
Neuroscience Institute, 11 Jalan Tam, Tolk Seng, Singapore, Singapore, 308433. tumapathi@yahoo.com
RESUMEN
/ SUMMARY: - BACKGROUND: Multifocal motor neuropathy is
a distinct clinical entity characterised by progressive, predominantly distal,
asymmetrical limb weakness and minimal sensory abnormality. The pathognomonic
feature of this condition is the presence of multiple partial motor nerve
conduction blocks. Controlled trials have demonstrated the efficacy of regular
intravenous immunoglobulin infusions. Immunosuppressive agents have been used
as primary, second-line or adjunctive agents for its treatment. This review was
undertaken to identify and review systematically randomised controlled trials
of immunosuppressive agents. The use of intravenous immunoglobulin will be the
subject of a separate review. OBJECTIVES: To provide the best available
evidence from randomised controlled trials on the role of immunosuppressive
agents for the treatment of multifocal motor neuropathy. SEARCH STRATEGY: The
Cochrane Neuromuscular Disease Group register was searched for all trials of
multifocal motor neuropathy published, using ‘multifocal motor neuropathy’ OR
‘chronic inflammatory demyelinating polyradiculoneuropathy’ OR ‘ conduction
block’ OR ‘ motor neuropathy’ AND ‘immunosuppressive agents’,
‘immunosuppressants’, ‘corticosteroids’, ‘plasma exchange’, ‘azathioprine’,
‘cyclophosphamide’, ‘cyclosporin’, ‘methotrexate’, and ‘mycophenolate’,
‘immunomodulatory agents’, ‘interferon’, ‘total lymphoid irradiation’ or ‘bone
marrow transplantation’ as search terms. In addition we searched MEDLINE,
EMBASE for 2000 and 2001 and CINAHL, LILACS for all years. SELECTION CRITERIA:
All randomised controlled trials and quasi-randomised clinical trials in which
allocation was not random but was intended to be unbiased (e.g. alternate
allocation) were to have been selected. Since no such trials were discovered,
all prospective and retrospective case series were included in ‘background’ or
‘discussion’ sections of the review. DATA COLLECTION AND ANALYSIS: All studies
on multifocal motor neuropathy or lower motor neuron weakness with conduction
block and no sensory abnormality were scrutinized for data on patients treated
with any form of immunosuppressive agents besides intravenous immunoglobulin.
The information on the outcome of treatment was then collated and summarised.
MAIN RESULTS: We found no randomised controlled trials of any immunosuppressive
agents for multifocal motor neuropathy. We summarised the results of
retrospective and prospective case series in the discussion of the review.
REVIEWER’S CONCLUSIONS: There are no randomised controlled trials to indicate
whether immunosuppressive agents are beneficial in multifocal motor
neuropathy. N. Ref:: 73
----------------------------------------------------
[48]
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
----------------------------------------------------
[49]
TÍTULO / TITLE: - Advances in allergic
skin diseases.
REVISTA
/ JOURNAL: - J Allergy Clin Immunol 2003 Mar;111(3
Suppl):S805-12.
AUTORES
/ AUTHORS: - Leung DY; Boguniewicz M
INSTITUCIÓN
/ INSTITUTION: - Division of Pediatric Allergy and
Immunology, National Jewish Medical and Research Center, Denver, CO 80206, USA.
RESUMEN
/ SUMMARY: - During the past year there have been
significant advances in our understanding of the mechanisms underlying allergic
skin diseases. This article reviews some of these advances in atopic dermatitis
and urticaria. The introduction of a new class of topical anti-inflammatory
medications, topical calcineurin inhibitors, has significantly increased our
treatment options and led to a rethinking of potential management approaches in
atopic dermatitis. N.
Ref:: 87
----------------------------------------------------
[50]
TÍTULO / TITLE: - Elidel (pimecrolimus)
cream 1%: a nonsteroidal topical agent for the treatment of atopic dermatitis.
REVISTA
/ JOURNAL: - J Allergy Clin Immunol 2003
May;111(5):1153-68.
AUTORES
/ AUTHORS: - Eichenfield LF; Beck L
INSTITUCIÓN
/ INSTITUTION: - Department of Pediatric and Adolescent
Dermatology, Children’s Hospital, San Diego, CA 92123, USA.
RESUMEN
/ SUMMARY: - Elidel is a steroid-free cream containing
a 1% strength of the topical immunomodulator pimecrolimus. Elidel was
specifically developed as a treatment for atopic dermatitis (AD) and is
approved for use in children as young as 2 years of age. The production of
inflammatory cytokines by activated T cells in skin is thought to play an
important role in the pathogenesis of AD. Elidel potently suppresses cytokine
production by dermal T cells without significantly impairing systemic immune
responses. Elidel does not cause steroid-associated local effects, such as
dermal atrophy, striae, or telangiectasia. In randomized controlled clinical
studies, twice-daily application of Elidel was shown to significantly improve
the signs and symptoms of AD in infants, children, and adults. The clinical
effect of Elidel on pruritus, the most troublesome symptom of AD, can be
observed within 1 week of therapy and is maintained for the duration of
treatment. Elidel is well tolerated; the risk of application-site reactions,
such as itching or burning, is comparable with that of the vehicle. Adverse
effects were generally mild in patients receiving Elidel and occurred at rates
comparable with those in patients receiving vehicle treatment. In a 1-year
study, Elidel significantly reduced the incidence of flares when used at the
first signs and symptoms of acute AD. As a result, overall corticosteroid use
to treat flares was significantly lower in patients using Elidel for early
intervention. N.
Ref:: 60
----------------------------------------------------
[51]
TÍTULO / TITLE: - Composite tissue
allotransplantation in chimeric hosts part II. A clinically relevant protocol
to induce tolerance in a rat model.
REVISTA
/ JOURNAL: - Transplantation 2003 Dec
15;76(11):1548-55.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000085288.12571.65
AUTORES
/ AUTHORS: - Prabhune KA; Gorantla VS; Perez-Abadia G;
Francois CG; Vossen M; Laurentin-Perez LA; Breidenbach WC; Wang GG; Anderson
GL; Pidwell DJ; Barker JH; Maldonado C
INSTITUCIÓN
/ INSTITUTION: - Division of Plastic and Reconstructive
Surgery, University of Louisville, Louisville, Kentucky, USA.
RESUMEN
/ SUMMARY: - BACKGROUND: We and others have shown that
mixed allogeneic chimerism induces donor-specific tolerance to composite tissue
allografts across major histocompatibility complex barriers without the need
for immunosuppression. However, a delay period between bone marrow
transplantation and limb allotransplantation is required, making such protocols
impractical for clinical application. This study eliminates this delay period
in a rat hind limb allotransplantation model by performing mixed allogeneic
chimerism induction and transplantation “simultaneously.” METHODS: Group 1
included controls in which naive Wistar Furth (WF) hosts received ACI hind
limbs. Group 2 included (ACI-->WF) chimeras that received limbs from
third-party donors (Fisher), and group 3 included chimeras that received irradiated
(1,050 cGy) ACI limbs. In group 4, WF hosts conditioned with 950 cGy received
irradiated (1,050 cGy) ACI limbs followed by infusion of 100 x 10(6) ACI
T-cell-depleted bone marrow cells and immunotherapy (tacrolimus and
mycophenolate mofetil) for 28 days. Group 5 animals received the same treatment
as group 4 animals without immunotherapy. RESULTS: The rats in groups 1 and 2
rejected their limbs within 10 days. Only one rat in group 4 survived to the
end of the study. Groups 3 and 5 demonstrated long-term limb survival without
rejection or graft-versus-host disease. High levels of donor chimerism
(>80%) were achieved and maintained throughout the study. Mixed lymphocyte
reaction assays in both groups revealed donor-specific hyporesponsiveness with
vigorous third-party reactivity. CONCLUSIONS: This study demonstrated that
infusion of donor bone marrow cells into conditioned hosts immediately after
limb transplantation results in stable mixed chimerism, robust tolerance, and
reliable limb allograft survival.
----------------------------------------------------
[52]
TÍTULO / TITLE: - Tacrolimus ointment for
the treatment of atopic dermatitis: clinical and pharmacologic effects.
REVISTA
/ JOURNAL: - Allergy Asthma Proc 2002
May-Jun;23(3):191-7.
AUTORES
/ AUTHORS: - Rico MJ; Lawrence I
INSTITUCIÓN
/ INSTITUTION: - Fujisawa Healthcare, Inc, 3 Pookway North
Deerfeild, IL 60022, USA.
RESUMEN
/ SUMMARY: - The topical immunomodulator tacrolimus
ointment has been shown to be safe and effective in the treatment of atopic
dermatitis in clinical trials involving over 16,000 patients. Clinical trial
results focusing on tacrolimus’ safety and efficacy are summarized. Minimal
systemic absorption results from topical application in patients with atopic
dermatitis. Although the exact mechanism of action of tacrolimus ointment in
atopic dermatitis is unknown, tacrolimus is known to inhibit up-regulation of
cytokine production following T cell activation and to decrease Fc epsilon RI
expression on dendritic antigen-presenting cells in skin. Additional mechanisms
of action of tacrolimus relevant in the pathogenesis of inflammatory skin
disorders are discussed. N.
Ref:: 27
----------------------------------------------------
[53]
TÍTULO / TITLE: - Immunosuppression
minimization: current and future trends in transplant immunosuppression.
REVISTA
/ JOURNAL: - J Am Soc Nephrol. Acceso gratuito al texto
completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.jasn.org/
●●
Cita: Journal of the American Society of Nephrology: <> 2003
Jul;14(7):1940-8.
AUTORES
/ AUTHORS: - Vincenti F
INSTITUCIÓN
/ INSTITUTION: - Kidney Transplant Service, University of
California-San Francisco, 505 Parnassus Avenue, M884, San Francisco, CA
94143-0780, USA. vincentif@surgery.ucsf.edu N. Ref:: 54
----------------------------------------------------
[54]
TÍTULO / TITLE: - mTOR as a positive
regulator of tumor cell responses to hypoxia.
REVISTA
/ JOURNAL: - Curr Top Microbiol Immunol
2004;279:299-319.
AUTORES
/ AUTHORS: - Abraham RT
INSTITUCIÓN
/ INSTITUTION: - Program in Signal Transduction Research,
The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA. abraham@burnham.org
RESUMEN
/ SUMMARY: - Rapamycin is a clinically approved
immunosuppressive agent that has recently shown promising antitumor activities
in human patients. In contrast to many conventional chemotherapeutic agents,
rapamycin displays a remarkably high level of selectivity for certain types of
tumors. The pharmacological activities of rapamycin are attributable to the
functional inhibition of a single target protein, termed the mammalian target
of rapamycin (mTOR). Because mTOR is widely expressed in both normal and
transformed cells, variations in mTOR expression levels are likely not a
primary determinant of tumor sensitivity to rapamycin. However, recent studies
highlighted an intriguing link between cancer cell sensitivity to rapamycin and
deregulated signaling through the phosphoinositide (PI) 3-kinase pathway. These
findings have prompted a search for cancer-related responses that are jointly
regulated by the PI 3-kinase signaling cascade and mTOR. The oxygen-regulated
transcription factor, hypoxia-induced factor (HIF)-1, has emerged as a
candidate target for both of these two highly interactive signaling proteins.
Here we review evidence that mTOR functions as a positive regulator of
HIF-1-dependent responses to hypoxic stress in human cancer cells. N. Ref:: 71
----------------------------------------------------
[55]
TÍTULO / TITLE: - Antiinflammatory
therapy for dry eye.
REVISTA
/ JOURNAL: - Am J Ophthalmol 2004 Feb;137(2):337-42.
●●
Enlace al texto completo (gratuito o de pago) 1016/j.ajo.2003.10.036
AUTORES
/ AUTHORS: - Pflugfelder SC
INSTITUCIÓN
/ INSTITUTION: - Ocular Surface Center, Department of
Ophthalmology, Baylor College of Medicine, Houston, Texas 77030, USA. stevenp@bcm.tmc.edu
RESUMEN
/ SUMMARY: - PURPOSE: To present evidence establishing
the relationship between inflammation and dry eye and supporting the use of
antiinflammatory therapy for dry eye. DESIGN: Analysis of literature. METHODS:
Research studies that evaluated inflammation in dry eye pathogenesis and
clinical trials of antiinflammatory therapies for dry eye were reviewed.
RESULTS: There is increasing evidence that decreased tear secretion, decreased
tear turnover, and desiccation promote inflammation on the ocular surface. An
increase in soluble mediators (cytokines and proteases) in the tear fluid,
adhesion molecule expression by the conjunctival epithelium, and T-cell
infiltration of the conjunctiva have been observed in dry eye patients. This
inflammation appears to have a role in the pathogenesis of the ocular surface epithelial
disease, termed keratoconjunctivitis sicca (KCS), that develops in dry eye.
Clinical improvement of KCS has been observed after therapy with
antiinflammatory agents including corticosteroids, cyclosporin and doxycycline.
Cyclosporin A emulsion was approved by the Food and Drug Administration as
therapy for dry eye. Randomized placebo-controlled FDA clinical trials showed
that cyclosporine A was superior to vehicle in stimulating aqueous tear
production, decreasing corneal punctuate fluorescein staining, reducing
symptoms of blurred vision, and decreasing artificial tear use in patients with
KCS. No ocular or systemic toxicity was observed from this medication.
CONCLUSIONS: Ocular surface and lacrimal gland inflammation has been identified
in dry eye that plays a role in the pathogenesis of KCS. Antiinflammatory
therapy has efficacy for treating KCS. Cyclosporin A is the first FDA approved
therapy for this indication. It improved signs and symptoms of KCS, and it is
safe for long-term use. N.
Ref:: 76
----------------------------------------------------
[56]
TÍTULO / TITLE: - TGF-beta expression in
protocol transplant liver biopsies: a comparative study between cyclosporine-A
(CyA) and tacrolimus (FK 506) immunosuppression.
REVISTA
/ JOURNAL: - Transplant Proc 2001
Feb-Mar;33(1-2):1378-80.
AUTORES
/ AUTHORS: - Mohamed MA; Burt AD; Robertson H; Kirby
JA; Talbot D
INSTITUCIÓN
/ INSTITUTION: - Transplant Immunobiology Group, Department
of Surgery, University of Newcastle, NE2 4HH, Newcastle Upon Tyne, UK.
----------------------------------------------------
[57]
TÍTULO / TITLE: - Review article: does
the use of immunosuppressive therapy in inflammatory bowel disease increase the
risk of developing lymphoma?
REVISTA
/ JOURNAL: - Aliment Pharmacol Ther 2001
Dec;15(12):1843-9.
AUTORES
/ AUTHORS: - Bebb JR; Logan RP
INSTITUCIÓN
/ INSTITUTION: - Division of Gastroenterology, University
Hospital, Nottingham, UK.
RESUMEN
/ SUMMARY: - Recent case reports have raised concerns
regarding the risks of non-Hodgkin’s lymphoma in patients with inflammatory
bowel disease treated with immunosuppressive agents. This evidence-based review
examines this issue from data derived from the use of immunosuppression in
other conditions (and inflammatory bowel disease). We conclude that, in
transplant (cardiac and renal) recipients, immunosuppression increases the risk
of non-Hodgkin’s lymphoma. For non-transplant patients (with psoriasis and
rheumatoid arthritis), debate remains as to whether the observed increase in the
incidence of non-Hodgkin’s lymphoma is due to drug or disease. For inflammatory
bowel disease per se, population studies show no significant increase in the
risk of non-Hodgkin’s lymphoma, with a relative risk of 1.3 (95% confidence
interval, 0.9-1.7) compared to expected rates, and several studies of immuno-
suppression in inflammatory bowel disease do not appear to confirm a
significant rate of lymphoma incidence. Reported cases of lymphoma from single
centres should be viewed with caution as evidence of increased risk. If any
association exists, it is likely to be of minimal clinical significance
compared to the established and more frequent risks of myelosuppression and
infection, and is unlikely to outweigh the benefit of immunosuppression in
inflammatory bowel disease. N.
Ref:: 43
----------------------------------------------------
[58]
TÍTULO / TITLE: - CD30+ T-cell lymphoma
in a patient with psoriasis treated with ciclosporin and infliximab.
REVISTA
/ JOURNAL: - Br J Dermatol 2003 Jul;149(1):170-3.
AUTORES
/ AUTHORS: - Mahe E; Descamps V; Grossin M; Fraitag S;
Crickx B
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology, Bichat-Claude
Bernard Hospital, 46 Rue Henri-Huchard, Paris Cedex 18, France. emmanuel.mahe@bch.ap-hop-paris.fr
RESUMEN
/ SUMMARY: - There is a known relationship between the
use of immunosuppressive therapies and the development of lymphoproliferative
malignancies. These lymphomas are mainly B-cell nonHodgkin’s lymphomas
associated with Epstein-Barr virus. Most cases concern classical
immunosuppressive treatments including ciclosporin and methotrexate. A
relationship between the new antitumour necrosis factor (TNF)-alpha agents and
lymphoproliferative malignancies is debated. Patients with psoriasis on
immunosuppressive therapies, mainly ciclosporin, are considered to have a low
risk of developing lymphoid proliferation. We report a patient with
erythrodermic psoriasis treated with ciclosporin and infliximab who developed a
CD30+ T-cell lymphoma. This lymphoma regressed after stopping these treatments.
In this case, the anti-TNF-alpha agent may have played a role in association
with ciclosporin in the development of the lymphoproliferative disorder.
Whereas the combination of anti-TNF-alpha therapies with methotrexate has been
well studied, their combination with ciclosporin has been evaluated only in a
few patients. Psoriatic patients who may require anti-TNF-alpha treatment have
often been or will be treated with ciclosporin. The combination of ciclosporin
and anti-TNF-alpha warrants further investigation. N. Ref:: 17
----------------------------------------------------
[59]
TÍTULO / TITLE: - European best practice
guidelines for renal transplantation. Section IV: Long-term management of the
transplant recipient. IV.5.8. Cardiovascular risks. Immunosuppressive therapy.
REVISTA
/ JOURNAL: - Nephrol Dial Transplant. Acceso gratuito
al texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://ndt.oupjournals.org/
●●
Cita: Nephrology Dialysis Transplantation: <> 2002;17 Suppl 4:30-1.
RESUMEN
/ SUMMARY: - GUIDELINE: Immunosuppressive therapies,
especially corticosteroids and anticalcineurin inhibitors; contribute to the
prevalence of cardiovascular risk factors, such as arterial hypertension,
hyperlipidaemia and hyperglycaemia, and this effect is dose dependent.
Reduction of the dose, withdrawal and/or switching to another drug could be
useful to control these risk factors.
----------------------------------------------------
[60]
TÍTULO / TITLE: - Cyclosporin trough
levels: is monitoring necessary during short-term treatment in psoriasis? A
systematic review and clinical data on trough levels.
REVISTA
/ JOURNAL: - Br J Dermatol 2002 Jul;147(1):122-9.
AUTORES
/ AUTHORS: - Heydendael VM; Spuls PI; Ten Berge IJ;
Opmeer BC; Bos JD; de Rie MA
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology, Academic
Medical Center, University of Amsterdam, PO Box 22660, the Netherlands.
RESUMEN
/ SUMMARY: - BACKGROUND: Cyclosporin is an effective
treatment for severe plaque psoriasis. Unfortunately, its use may be limited by
time- and dose-related nephrotoxicity. Serum trough levels may be useful for
monitoring the risk of nephrotoxicity. OBJECTIVES: To determine whether
monitoring of trough levels is necessary in psoriasis patients undergoing
short-term treatment with cyclosporin. METHODS: A computerized and manual literature
search identified studies on adults with plaque-type psoriasis treated with
cyclosporin < or = 5 mg kg-1 daily, in which trough levels were measured in
whole blood. Number of patients, treatment duration, formulation and dosage,
renal function tests and trough levels were extracted. The association between
renal function and trough levels was investigated. Additionally, in a
randomized controlled trial on cyclosporin vs. methotrexate in moderate to
severe psoriasis, cyclosporin trough levels were measured frequently in 20
patients during 12 weeks of treatment. The Pearson correlation coefficient
between serum creatinine and cyclosporin trough levels was calculated. RESULTS:
Fifty-six articles were found concerning cyclosporin trough level measurements
in psoriasis patients, of which eight were analysed. Many studies were excluded
due to inappropriate cyclosporin dosages used. As data were heterogeneous and
lacked various key parameters, a correlation study and a meta-analysis could
not be performed. Instead, a quantitative description of the literature was
given. No high mean trough levels or elevations of serum creatinine were
described. In our clinical study, all the mean trough levels in 17 patients
treated with cyclosporin 3 mg kg-1 daily were within the therapeutic range
(< 200 ng mL-1). Elevated trough levels were found in two of three patients
treated with cyclosporin 3-5 mg kg-1 daily. No signs of renal dysfunction were
seen. CONCLUSIONS: The literature does not provide a definitive answer on
whether monitoring cyclosporin trough levels in patients with psoriasis should
be standard practice. Our own data show no need for cyclosporin trough level
monitoring during short-term treatment with cyclosporin 3 mg kg-1 daily.
However, when cyclosporin doses are > 3 mg kg-1 daily, monitoring may be
indicated. N. Ref:: 32
----------------------------------------------------
[61]
TÍTULO / TITLE: - Elucidating TOR
signaling and rapamycin action: lessons from Saccharomyces cerevisiae.
REVISTA
/ JOURNAL: - Microbiol Mol Biol Rev. - Acceso gratuito
al texto completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://mmbr.asm.org/
●●
Cita: Microbiology & Molecular Biology Reviews: <> 2002
Dec;66(4):579-91, table of contents.
AUTORES
/ AUTHORS: - Crespo JL; Hall MN
INSTITUCIÓN
/ INSTITUTION: - Division of Biochemistry, Biozentrum,
University of Basel, CH-4056 Basel, Switzerland.
RESUMEN
/ SUMMARY: - TOR (target of rapamycin) is a
phosphatidylinositol kinase-related protein kinase that controls cell growth in
response to nutrients. Rapamycin is an immunosuppressive and anticancer drug
that acts by inhibiting TOR. The modes of action of TOR and rapamycin are
remarkably conserved from S. cerevisiae to humans. The current understanding of
TOR and rapamycin is derived largely from studies with S. cerevisiae. In this
review, we discuss the contributions made by S. cerevisiae to understanding
rapamycin action and TOR function. N.
Ref:: 171
----------------------------------------------------
[62]
TÍTULO / TITLE: - Subcutaneous
panniculitic T-cell lymphoma in children: response to combination therapy with
cyclosporine and chemotherapy.
REVISTA
/ JOURNAL: - J Am Acad Dermatol 2004 Feb;50(2
Suppl):S18-22.
●●
Enlace al texto completo (gratuito o de pago) 1016/S0190
AUTORES
/ AUTHORS: - Shani-Adir A; Lucky AW; Prendiville J;
Murphy S; Passo M; Huang FS; Paller AS
INSTITUCIÓN
/ INSTITUTION: - Division of Dermatology, Children’s
Memorial Hospital, 2300 Children’s Plaza, Chicago, IL 60614, USA.
RESUMEN
/ SUMMARY: - We describe 2 adolescent boys with facial
swelling and/or subcutaneous nodules and fever. Extensive evaluation, including
several biopsy specimens, led to a diagnosis of subcutaneous panniculitic
T-cell lymphoma, an entity rarely seen in children. Both patients were treated
with oral cyclosporine in an effort to suppress the cytokine release from
T-cells that has been thought to induce the hemophagocytic syndrome. The
patients responded dramatically to cyclosporine treatment with defervescence of
the fever and reduction in number and size of the subcutaneous nodules.
Subsequent therapy with multidrug chemotherapy achieved complete remission in
the first patient. This report suggests the value of cyclosporine as a
first-line agent coupled with chemotherapy in the treatment of patients with
subcutaneous panniculitic T-cell lymphoma. A clinicopathologic review of 8
described pediatric cases of subcutaneous panniculitic T-cell lymphoma is also
presented. N. Ref:: 15
----------------------------------------------------
[63]
TÍTULO / TITLE: - Structures of
calcineurin and its complexes with immunophilins-immunosuppressants.
REVISTA
/ JOURNAL: - Biochem Biophys Res Commun 2003 Nov
28;311(4):1095-102.
AUTORES
/ AUTHORS: - Ke H; Huai Q
INSTITUCIÓN
/ INSTITUTION: - Department of Biochemistry and Biophysics
and Lineberger Comprehensive Cancer Center, The University of North Carolina,
Chapel Hill, NC 27599-7260, USA. hke@med.unc.edu
RESUMEN
/ SUMMARY: - Calcineurin (CN) is a
Ca(2+)/calmodulin-dependent serine/threonine protein phosphatase and is
involved in many physiological processes such as T-cell activation and cardiac
hypertrophy. The crystal structures of CN and its complexes with FKBP12-FK506
and cyclophilin-cyclosporin showed that the two structurally unrelated
immunophilins-immunosuppressants bind to a common composite surface made up of
the residues from both catalytic subunit and regulatory subunit of CN. The
recognition of the immunophilins and immunosuppressive drugs is achieved by
common but few distinct CN residues. However, the binding pattern of
FKBP12-FK506 such as hydrogen bonding is significantly different from that of
CyPA-CsA. This common but distinct recognition may indicate capacity of the
composition surface for binding of other inhibitory proteins. The recognition
site and the active site are adjacent and form an “L” shaped cleft. This
implies that the immunophilin recognition site may also serve as a recognition
site to define the narrow substrate specificity of calcineurin. N. Ref:: 61
----------------------------------------------------
[64]
TÍTULO / TITLE: - European best practice
guidelines for renal transplantation. Section IV: Long-term management of the
transplant recipient. IV.3.2. Long-term immunosuppression. Therapy conversion.
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 4:20-1.
RESUMEN
/ SUMMARY: - GUIDELINE: Conversion of immunosuppressive
drug therapy is recommended to avoid or reduce drug-specific adverse effects,
and is generally safe for long-term graft outcome.
----------------------------------------------------
[65]
TÍTULO / TITLE: - Multidrug resistance
reversal agents.
REVISTA
/ JOURNAL: - J Med Chem 2003 Nov 6;46(23):4805-17.
●●
Enlace al texto completo (gratuito o de pago) 1021/jm030183a
AUTORES
/ AUTHORS: - Robert J; Jarry C
INSTITUCIÓN
/ INSTITUTION: - Institut Bergonie, 229, Cours de
l’Argonne, 33076 Bordeaux Cedex, France. robert@bergonie.org N. Ref:: 151
----------------------------------------------------
[66]
TÍTULO / TITLE: - Prospects for treatment
of paraquat-induced lung fibrosis with immunosuppressive drugs and the need for
better prediction of outcome: a systematic review.
REVISTA
/ JOURNAL: - Qjm. Acceso gratuito al texto completo a
partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://qjmed.oupjournals.org/
●●
Cita: QJM: <> 2003 Nov;96(11):809-24.
AUTORES
/ AUTHORS: - Eddleston M; Wilks MF; Buckley NA
INSTITUCIÓN
/ INSTITUTION: - Centre for Tropical Medicine, Nuffield
Department of Clinical Medicine, University of Oxford, UK. eddlestonm@eureka.lk
RESUMEN
/ SUMMARY: - BACKGROUND: Acute paraquat self-poisoning
is a significant problem in parts of Asia, the Pacific and the Caribbean.
Ingestion of large amounts of paraquat results in rapid death, but smaller
doses often cause a delayed lung fibrosis that is usually fatal.
Anti-neutrophil (‘immunosuppressive’) treatment has been recommended to prevent
lung fibrosis, but there is no consensus on efficacy. Aim: To review the
evidence for the use of immunosuppression in paraquat poisoning, and to
identify validated prognostic systems that would allow the use of data from
historical control studies and the future identification of patients who might
benefit from immunosuppression. DESIGN:Systematic review. METHODS: We searched
PubMed, Embase and Cochrane databases for ‘paraquat’ together with ‘poisoning’
or ‘overdose’. We cross-checked references and contacted experts, and searched
on [www.google.com] and [www.yahoo.com] using ‘paraquat’, ‘cyclophosphamide’,
‘methylprednisolone’ and ‘prognosis’. RESULTS: We found ten clinical studies of
immunosuppression in paraquat poisoning. One was a randomized controlled trial
(RCT). Seven used historical controls only; the other two were small (n = 1 and
n = 4). Mortality in controls and patients varied markedly between studies.
Three of the seven non-RCT controlled studies measured plasma paraquat;
analysis using Proudfoot’s or Hart’s nomograms did not suggest that
immunosuppression increased survival in these studies. Of 16 prognostic systems
for paraquat poisoning, none has been independently validated in a large
cohort. DISCUSSION: The authors of the RCT have performed valuable and
difficult research, but their results are hypothesis-forming rather than
conclusive; elsewhere, the use of historical controls is problematic. In the
absence of a validated prognostic marker, a large RCT of immunosuppression
using death as the primary outcome is required. This RCT should also
prospectively test and validate the available prognostic methods, so that
future patients can be selected for this and other therapies on admission. N. Ref:: 57
----------------------------------------------------
[67]
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
----------------------------------------------------
[68]
TÍTULO / TITLE: - Review article: the
risk of lymphoma associated with inflammatory bowel disease and
immunosuppressive treatment.
REVISTA
/ JOURNAL: - Aliment Pharmacol Ther 2001
Aug;15(8):1101-8.
AUTORES
/ AUTHORS: - Aithal GP; Mansfield JC
INSTITUCIÓN
/ INSTITUTION: - Department of Gastroenterology, University
of Newcastle, Newcastle upon Tyne, UK.
RESUMEN
/ SUMMARY: - Lymphoma complicating inflammatory bowel
disease is well described. Whether the risk of lymphoma is increased by
immunosuppressive treatment with azathioprine, 6-mercaptopurine or infliximab
is a common concern among patients and physicians considering using these
agents. This review aims to quantify the lymphoma risk in inflammatory bowel
disease and the added risk attributable to these treatments. The evidence from
published cases is that lymphomas occur at sites of active inflammatory bowel
disease more often than expected for this to be a chance association. Studies
on inflammatory bowel disease populations are conflicting, with some follow-up
studies from large inflammatory bowel disease clinics showing an increase in
lymphoma incidence, while other population-based studies show little or no
increase in risk of lymphoma. A small increase in lymphoma risk in inflammatory
bowel disease, perhaps 2-3-fold, may be compatible with both sets of data.
Studies of the risks associated with immuno- suppression are less satisfactory,
with smaller numbers of patients and relatively short follow-up. The available
evidence would support a further increase in lymphoma risk associated with
immunosuppressive treatment in inflammatory bowel disease of around fivefold
compared to no immunosuppressive use, and tenfold compared to the general
population. The risks appear to be less than that associated with renal and
hepatic transplant-related immunosuppression. Infliximab treatment is still too
new to make a full assessment of its long-term safety, but post-marketing
surveillance currently suggests that lymphoma risk may not be any greater than
that associated with azathioprine and 6-mercaptopurine. Population-wide
surveillance for lymphoma in inflammatory bowel disease would be required to
narrow the confidence intervals on these estimates of lymphoma risk in
inflammatory bowel disease and immunosuppressive treatment. N. Ref:: 54
----------------------------------------------------
[69]
TÍTULO / TITLE: - A thorough systematic
review of treatments for atopic eczema.
REVISTA
/ JOURNAL: - Arch Dermatol 2001 Dec;137(12):1635-6.
AUTORES
/ AUTHORS: - Bigby M
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology, Harvard Medical
School, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215,
USA. mbigby@caregroup.harvard.edu N. Ref:: 420
----------------------------------------------------
[70]
TÍTULO / TITLE: - Review article: medical
treatment of active Crohn’s disease.
REVISTA
/ JOURNAL: - Aliment Pharmacol Ther 2002 Jul;16 Suppl
4:35-9.
AUTORES
/ AUTHORS: - Scribano ML; Prantera C
INSTITUCIÓN
/ INSTITUTION: - Division of Gastroenterology, Azienda
Ospedaliera S.Camillo-Forlanini, Rome, Italy.
RESUMEN
/ SUMMARY: - Crohn’s disease, a heterogeneous
inflammatory process that can affect various sites in the gut, presents an
ongoing management challenge for the clinician. The treatment of active disease
and complications is one of the main goals in the therapy of this disease. New
therapies are aimed at delivering the active compounds to the diseased site,
reduction or suppression of enteral flora and modulation of more focal targets
within the immune response. The use of antibiotics in the therapy of Crohn’s
disease is gaining popularity, on the grounds that intestinal bacteria may play
a role in the pathogenesis of Crohn’s disease lesions. Metronidazole is one of
the most widely used antibiotics, especially in the treatment of perianal
disease. Corticosteroids are the mainstays of medical treatment in active
Crohn’s disease and induce the remission of symptoms in about 60-80% of
patients. The use of immunosuppressive agents, such as cyclosporine and
methotrexate, in patients with active disease resistant to standard therapy has
gained acceptance in recent years. With new therapies the outlook for patients
with Crohn’s disease is more optimistic than it has been for a long time. N. Ref:: 39
----------------------------------------------------
[71]
TÍTULO / TITLE: - Patient management by
Neoral C(2) monitoring: an international consensus statement.
REVISTA
/ JOURNAL: - Transplantation 2002 May 15;73(9
Suppl):S12-8.
AUTORES
/ AUTHORS: - Levy G; Thervet E; Lake J; Uchida K
INSTITUCIÓN
/ INSTITUTION: - Multiorgan Transplant Program, Toronto
General Hospital, 621 University Avenue, 10NU-116, Toronto, Ontario M5G 2C4,
Canada. N. Ref:: 36
----------------------------------------------------
[72]
TÍTULO / TITLE: - Current and novel
immunosuppressive therapy for autoimmune hepatitis.
REVISTA
/ JOURNAL: - Hepatology 2002 Jan;35(1):7-13.
●●
Enlace al texto completo (gratuito o de pago) 1053/jhep.2002.30991
AUTORES
/ AUTHORS: - Heneghan MA; McFarlane IG
INSTITUCIÓN
/ INSTITUTION: - Division of Gastroenterology, Duke
University Medical Center, Durham NC 27710, USA. heneg003@mc.duke.edu
RESUMEN
/ SUMMARY: - Corticosteroids alone or in conjunction
with azathioprine is the treatment of choice in patients with autoimmune
hepatitis (AIH) and results in remission induction in over 80% of patients.
Sustained response to therapy may result in substantial regression of fibrosis
even in advanced cases. The outcome of rapid withdrawal of immunosuppression is
disease relapse in many patients. Consequently, the use of 2 mg/kg/d of
azathioprine as a sole agent to maintain remission has been widely accepted in
clinical practice. Persistent severe laboratory abnormalities or histologic
abnormalities such as bridging necrosis or multilobular necrosis are absolute
indications for treatment based on controlled clinical trials, but debate
exists as to whether all patients with AIH need treatment. Examination of liver
tissue remains the best method of evaluating both treatment response and need
for treatment in patients who have little biochemical activity. Alternative
strategies in patients who have failed to achieve remission on “standard
therapy” of corticosteroids with or without azathioprine or patients with drug
toxicity include the use of cyclosporine, tacrolimus, or mycophenolate mofetil.
Liver transplantation is the treatment of choice in managing decompensated
disease. In this review we examine current management strategies of AIH, and
evaluate available data pertaining to the use of novel immunosuppressive agents
in this condition. N.
Ref:: 50
----------------------------------------------------
[73]
TÍTULO / TITLE: - Cyclosporin as an oral
corticosteroid sparing agent in stable asthma.
REVISTA
/ JOURNAL: - Cochrane Database Syst Rev
2001;(2):CD002993.
AUTORES
/ AUTHORS: - Evans DJ; Cullinan P; Geddes DM
INSTITUCIÓN
/ INSTITUTION: - Respiratory Centre, St Mary’s Hospital,
Milton Road, Portsmouth, UK, PO3 6AD. david.evans@smail01.porthosp.swest.nhs.uk
RESUMEN
/ SUMMARY: - BACKGROUND: Patients with chronic severe
asthma are often dependent on the long term prescription of oral
corticosteroids. The use of steroids is associated with serious side effects.
Physicians treating such patients continue to search for alternative therapies
that reduce the need for chronic dosing with oral steroids. Cyclosporin is an
immunosuppressive agent and has benefits in the treatment of a number of inflammatory
disorders. It has therefore been identified as an potentially useful agent in
the treatment of chronic severe asthma both in terms of possible efficacy and
as a steroid sparing agent. OBJECTIVES: The objective of this review was to
assess the effects of adding cyclosporin to oral steroids in the treatment of
chronic steroid dependent asthmatics. SEARCH STRATEGY: The Cochrane Airways
Group trials register and reference lists of identified articles were searched.
SELECTION CRITERIA: Randomised trials looking at the addition of cyclosporin
compared to placebo in adult steroid dependent asthmatics. DATA COLLECTION AND
ANALYSIS: Trial quality was assessed and data extraction was carried out by two
reviewers independently. Study authors were contacted for missing information.
MAIN RESULTS: Three trials fulfilled the criteria for inclusion in the review
and a total of 106 patients were recruited into these studies. Data from 98
patients could be analysed. There was a small but significant treatment effect
for cyclosporin in terms of steroid dose reduction (SMD -0.5, 95% CI -1.0,
-0.04). No meta-analyses could be performed for measures of lung function
although one study showed small, but significant improvements in lung
spirometry. REVIEWER’S CONCLUSIONS: The changes with cyclosporin are small and
of questionable clinical significance. Given the side effects of cyclosporin,
the evidence available does not recommend routine use of this drug in the
treatment of oral corticosteroid dependent asthma. N. Ref:: 11
----------------------------------------------------
[74]
TÍTULO / TITLE: - Calcineurin
inhibitor-free CD28 blockade-based protocol protects allogeneic islets in
nonhuman primates.
REVISTA
/ JOURNAL: - Diabetes. Acceso gratuito al texto
completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://diabetes.diabetesjournals.org/
●●
Cita: Diabetes: <> 2002 Feb;51(2):265-70.
AUTORES
/ AUTHORS: - Adams AB; Shirasugi N; Durham MM; Strobert
E; Anderson D; Rees P; Cowan S; Xu H; Blinder Y; Cheung M; Hollenbaugh D;
Kenyon NS; Pearson TC; Larsen CP
INSTITUCIÓN
/ INSTITUTION: - Emory Transplant Center, Department of
Surgery, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
RESUMEN
/ SUMMARY: - Recent success using a steroid-free
immunosuppressive regimen has renewed enthusiasm for the use of islet
transplantation to treat diabetes. Toxicities associated with the continued use
of a calcineurin inhibitor may limit the wide-spread application of this
therapy. Biological agents that block key T-cell costimulatory signals, in
particular the CD28 pathway, have demonstrated extraordinary promise in animal
models. LEA29Y (BMS-224818), a mutant CTLA4-Ig molecule with increased binding
activity, was evaluated for its potential to replace tacrolimus and protect
allogeneic islets in a preclinical primate model. Animals received either the
base immunosuppression regimen (rapamycin and anti-IL-2R monoclonal antibody
[mAb]) or the base immunosuppression and LEA29Y. Animals receiving the
LEA29Y/rapamycin/anti-IL-2R regimen (n = 5) had significantly prolonged islet
allograft survival (204, 190, 216, 56, and >220 days). In contrast, those
animals receiving the base regimen alone (n = 2) quickly rejected the transplanted
islets at 1 week (both at 7 days). The LEA29Y-based regimen prevented the
priming of anti-donor T- and B-cell responses, as detected by interferon-gamma
enzyme-linked immunospot and allo-antibody production, respectively. The
results of this study suggest that LEA29Y is a potent immunosuppressant that
can effectively prevent rejection in a steroid-free immunosuppressive protocol
and produce marked prolongation of islet allograft survival in a preclinical
model.
----------------------------------------------------
[75]
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
----------------------------------------------------
[76]
TÍTULO / TITLE: - New immunosuppressive
agent: expectations and controversies.
REVISTA
/ JOURNAL: - Transplantation 2003 Mar 27;75(6):741-2.
AUTORES
/ AUTHORS: - Alsina J; Grinyo JM
INSTITUCIÓN
/ INSTITUTION: - Department of Nephrology, Bellvitge
Hospital, Barcelona, España. N.
Ref:: 5
----------------------------------------------------
[77]
TÍTULO / TITLE: - Role of leucine in the
regulation of mTOR by amino acids: revelations from structure-activity studies.
REVISTA
/ JOURNAL: - J Nutr. Acceso gratuito al texto completo
a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.nutrition.org/
●●
Cita: Journal of Nutrition: <> 2001 Mar;131(3):861S-865S.
AUTORES
/ AUTHORS: - Lynch CJ
INSTITUCIÓN
/ INSTITUTION: - Department of Cellular and Molecular
Physiology, The Pennsylvania State University College of Medicine, 500
University Drive, Hershey, PA 17033, USA. clynch@psu.edu
RESUMEN
/ SUMMARY: - In this study an overview is presented of
the mTOR signaling pathway and its regulation by amino acids, particularly
L-leucine. Our laboratory is studying amino acid regulation of mTOR in
adipocytes. Potential roles for mTOR in adipocytes that were previously posited
include hypertrophic growth, leptin secretion, protein synthesis and adipose
tissue morphogenesis. A current area of interest in the field is how amino
acids regulate mTOR and which amino acids are regulatory. Revelations
concerning mechanism and recognition are emerging from different laboratories
that examined the structural requirements for stimulation and inhibition of the
mTOR signaling pathway by leucine and amino acid analogs. In adipocytes and
some other cell types, leucine appears to be the main regulatory amino acid.
However, this is not uniformly the case. In those cells where mTOR is regulated
by several amino acids, there is evidence that the mechanism of mTOR activation
may be different from cells where mainly leucine is regulatory. Furthermore, in
tissues where leucine regulates mTOR, the possible existence of different
tissue-specific leucine recognition sites may be indicated. N. Ref:: 47
----------------------------------------------------
[78]
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
----------------------------------------------------
[79]
TÍTULO / TITLE: - Current
disease-modifying therapies in multiple sclerosis.
REVISTA
/ JOURNAL: - Semin Neurol 2003 Jun;23(2):133-46.
●●
Enlace al texto completo (gratuito o de pago) 1055/s-2003-41138
AUTORES
/ AUTHORS: - Kieseier BC; Hartung HP
INSTITUCIÓN
/ INSTITUTION: - Department of Neurology,
Heinrich-Heine-University, Moorenstrasse 5, 40225 Dusseldorf, Germany.
RESUMEN
/ SUMMARY: - In recent years, the usefulness of
interferon beta and glatiramer acetate in the treatment of relapsing-remitting
multiple sclerosis (RRMS) has been established. Interferon beta has also been
shown to be efficacious in secondary-progressive multiple sclerosis (SPMS) as
well as in patients with isolated syndromes at risk to develop clinically
definite multiple sclerosis (MS). Mitoxantrone is another disease-modifying
drug that is available for SPMS and severe cases of RRMS. The clinical utility
of disease-modifying agents in MS will be reviewed with respect to the
anti-inflammatory, immunomodulatory, and immunosuppressive treatments that are
currently available. Symptomatic therapies will not be considered. N. Ref:: 99
----------------------------------------------------
[80]
- Castellano -
TÍTULO / TITLE:Las inmunofilinas: agentes
neuroprotectores y promotores de la regeneracion neural. Immunophilins:
neuroprotective agents and promoters of neural regeneration.
REVISTA
/ JOURNAL: - Neurologia. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.stmeditores.com/Revistas/ffasciculo.php?Mw==&MTk=&MjUy
●●
Cita: Neurologia: <> 2002 Apr;17(4):200-13.
AUTORES
/ AUTHORS: - Udina E; Navarro X
INSTITUCIÓN
/ INSTITUTION: - Grupo de Neuroplasticidad y Regeneracion,
Departamento de Biologia Celular, Fisiologia e Inmunologia, Universitat Autonoma
de Barcelona, Bellaterra, España.
RESUMEN
/ SUMMARY: - Immunophilins are a family of proteins
mainly known because they act as receptors of the immunosuppressant drugs
cyclosporin A (CsA) and FK506. Immunophilins serve several general functions,
including regulation of mitochondrial permeability, modulation of ion channels
stability and acting as chaperones for a variety of proteins. However,
immunophilins are also present at high density in the nervous system. CsA,
FK506 and other derivatives inhibit the function of immunophilins and, through
bloking or activating several intracellular pathways, it has been shown that
they exert neuroprotective effects in different experimental models of
ischemia, Parkinson’s disease and excitotoxic insults. Moreover, FK506 also has
neuroregenerative effects, by enhancing the axonal regeneration rate after
lesions of the peripheral nervous system. The development of new agents that
selectively bind to immunophilins opens new interesting perspectives for the
therapy of degenerative diseases and injuries of the nervous system. N. Ref:: 100
----------------------------------------------------
[81]
TÍTULO / TITLE: - Immunoablation followed
or not by hematopoietic stem cells as an intense therapy for severe autoimmune
diseases. New perspectives, new problems.
REVISTA
/ JOURNAL: - Haematologica. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://db.doyma.es/
●●
Cita: Haematologica: <> 2001 Apr;86(4):337-45.
AUTORES
/ AUTHORS: - Marmont AM N. Ref:: 127
----------------------------------------------------
[82]
TÍTULO / TITLE: - mTOR as a target for
cancer therapy.
REVISTA
/ JOURNAL: - Curr Top Microbiol Immunol
2004;279:339-59.
AUTORES
/ AUTHORS: - Houghton PJ; Huang S
INSTITUCIÓN
/ INSTITUTION: - Department of Molecular Pharmacology, St.
Jude Children’s Research Hospital, 332 N. Lauderdale, Memphis, TN 38105-2794,
USA. peter.houghton@stjude.org
RESUMEN
/ SUMMARY: - The target of rapamycin, mTOR, acts as a
sensor for mitogenic stimuli, such as insulin-like growth factors and cellular
nutritional status, regulating cellular growth and division. As many tumors are
driven by autocrine or paracrine growth through the type-I insulin-like growth
factor receptor, mTOR is potentially an attractive target for molecular-targeted
treatment. Further, a rationale for anticipating tumor-selective activity based
on transforming events frequently identified in malignant disease is becoming
established. N.
Ref:: 73
----------------------------------------------------
[83]
TÍTULO / TITLE: - Serine-threonine
protein phosphatase inhibitors: development of potential therapeutic
strategies.
REVISTA
/ JOURNAL: - J Med Chem 2002 Mar 14;45(6):1151-75.
AUTORES
/ AUTHORS: - McCluskey A; Sim AT; Sakoff JA
INSTITUCIÓN
/ INSTITUTION: - School of Biological & Chemical
Science, Medicinal Chemistry Group, The University of Newcastle, Callaghan, NSW
2308, Australia. amcclusk@mail.newcastle.edu.au N. Ref:: 329
----------------------------------------------------
[84]
TÍTULO / TITLE: - Inflammatory
myopathies: clinical, diagnostic and therapeutic aspects.
REVISTA
/ JOURNAL: - Muscle Nerve 2003 Apr;27(4):407-25.
●●
Enlace al texto completo (gratuito o de pago) 1002/mus.10313
AUTORES
/ AUTHORS: - Mastaglia FL; Garlepp MJ; Phillips BA;
Zilko PJ
INSTITUCIÓN
/ INSTITUTION: - Centre for Neuromuscular and Neurological
Disorders, University of Western Australia, Queen Elizabeth II Medical Centre,
Nedlands, Australia. flmast@cyllene.uwa.edu.au
RESUMEN
/ SUMMARY: - The three major forms of immune-mediated
inflammatory myopathy are dermatomyositis (DM), polymyositis (PM), and
inclusion-body myositis (IBM). They each have distinctive clinical and
histopathologic features that allow the clinician to reach a specific diagnosis
in most cases. Magnetic resonance imaging is sometimes helpful, particularly if
the diagnosis of IBM is suspected but has not been formally evaluated.
Myositis-specific antibodies are not helpful diagnostically but may be of
prognostic value; most antibodies have low sensitivity. Muscle biopsy is
mandatory to confirm the diagnosis of an inflammatory myopathy and to allow
unusual varieties such as eosinophilic, granulomatous, and parasitic myositis,
and macrophagic myofasciitis, to be recognized. The treatment of the
inflammatory myopathies remains largely empirical and relies upon the use of
corticosteroids, immunosuppressive agents, and intravenous immunoglobulin, all
of which have nonselective effects on the immune system. Further controlled
clinical trials are required to evaluate the relative efficacy of the available
therapeutic modalities particularly in combinations, and of newer
immunosuppressive agents (mycophenolate mofetil and tacrolimus) and
cytokine-based therapies for the treatment of resistant cases of DM, PM, and
IBM. Improved understanding of the molecular mechanisms of muscle injury in the
inflammatory myopathies should lead to the development of more specific forms
of immunotherapy for these conditions. N.
Ref:: 256
----------------------------------------------------
[85]
TÍTULO / TITLE: - Mitochondrial
permeability transition in acute neurodegeneration.
REVISTA
/ JOURNAL: - Biochimie 2002 Feb-Mar;84(2-3):241-50.
AUTORES
/ AUTHORS: - Friberg H; Wieloch T
INSTITUCIÓN
/ INSTITUTION: - Laboratory for Experimental Brain
Research, Wallenberg Neuroscience Center, BMC A13, 221 84 Lund, Sweden.
RESUMEN
/ SUMMARY: - Acute neurodegeneration in man is
encountered during and following stroke, transient cardiac arrest, brain
trauma, insulin-induced hypoglycemia and status epilepticus. All these severe
clinical conditions are characterized by neuronal calcium overload, aberrant
cell signaling, generation of free radicals and elevation of cellular free
fatty acids, conditions that favor activation of the mitochondrial permeability
transition pore (mtPTP). Cyclosporin A (CsA) and its analog
N-methyl-valine-4-cyclosporin A (MeValCsA) are potent blockers of the mtPTP and
protect against neuronal death following excitotoxicity and oxygen glucose
deprivation. Also, CsA and MeValCsA diminish cell death following cerebral
ischemia, trauma, and hypoglycemia. Here we present data that strongly imply
the mtPT in acute neurodegeneration in vivo. Compounds that readily pass the
blood-brain-barrier (BBB) and block the mtPT may be neuroprotective in
stroke. N. Ref:: 100
----------------------------------------------------
[86]
TÍTULO / TITLE: - Macrolactam
immunomodulators for topical treatment of inflammatory skin diseases.
REVISTA
/ JOURNAL: - J Am Acad Dermatol 2001 Nov;45(5):736-43.
AUTORES
/ AUTHORS: - Bornhovd E; Burgdorf WH; Wollenberg A
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology and Allergology,
Ludwig-Maximilians University, Munich, Germany.
RESUMEN
/ SUMMARY: - The immunomodulatory macrolactams provide
an alternative to glucocorticosteroids for the topical treatment of atopic
dermatitis and other inflammatory dermatoses. Tacrolimus (FK506), as well as
the newer ascomycin derivative ASM 981 (pimecrolimus), penetrate the inflamed
epidermis and are suitable for topical therapy. Both substances inhibit the
transcription of proinflammatory cytokine genes such as interleukin 2, which
are dependent on the nuclear factor NF-AT. They block the catalytic function of
calcineurin, which leads to the inhibition of the transport of the cytoplasmic
component of NF-AT to the cell nucleus. Multicenter, randomized, double-blind clinical
trials with topical formulations have shown the efficacy of both substances in
moderate to severe atopic dermatitis. A review is presented of the biochemical
and cell biologic properties, mode of action, pharmacokinetic data, side
effects, results of the clinical trials, and further indications for tacrolimus
and ASM 981, along with an overview of the related substances cyclosporine and
sirolimus (rapamycin). N.
Ref:: 72
----------------------------------------------------
[87]
TÍTULO / TITLE: - The use of high dose
immunoablative therapy with hematopoietic stem cell support therapy in the
treatment of severe autoimmune diseases.
REVISTA
/ JOURNAL: - Int J Hematol 2002 Aug;76 Suppl 1:218-22.
AUTORES
/ AUTHORS: - Tyndall A; Gratwohl A N. Ref:: 13
----------------------------------------------------
[88]
TÍTULO / TITLE: - How should the
immunosuppressive regimen be managed in patients with established chronic
allograft failure?
REVISTA
/ JOURNAL: - Kidney Int Suppl 2002 May;(80):68-72.
AUTORES
/ AUTHORS: - Danovitch GM
INSTITUCIÓN
/ INSTITUTION: - Division of Nephrology, UCLA School of
Medicine, USA. gdanovitch@mednet.ucla.edu N. Ref:: 25
----------------------------------------------------
[89]
TÍTULO / TITLE: - Calcineurin-free
protocols with basiliximab induction allow patients included in “old to old”
programs achieve standard kidney transplant function.
REVISTA
/ JOURNAL: - Transplant Proc 2003 Jun;35(4):1326-7.
AUTORES
/ AUTHORS: - Emparan C; Laukotter M; Wolters H; Dame C;
Heidenreich S; Senninger N
INSTITUCIÓN
/ INSTITUTION: - Department of Surgery, Division of
Transplantation, Uniklinikum Munster, Munster, Germany. cemparan@teleline.es
RESUMEN
/ SUMMARY: - INTRODUCTION: The EuroTransplant “old to
old” program establishes that patients older than 60 years can receive offers
of organs from donors older than 60 years. The compromised function of these
organs makes it a priority to preserve their initial kidney function.
HYPOTHESIS: Calcineurin-sparing protocols using anti-IL-2 receptor (IL-2R)
antibody induction (Simulect) may benefit initial kidney function in these
patients, as assessed by the rates of delayed graft function and of rejection
during the first month after transplant. PATIENTS AND METHODS: A cohort of 15
consecutive elderly patients were prospectively compared with 30 cadaveric
kidney transplants in younger recipients. Study patients were induced with
Simulect (20 mg, 30 minutes before reperfusion and 4 days after
transplantation) and steroids, delaying the introduction of CsA until the serum
creatinine was below 3 mg/dL. The other cohort of patients were
immunosuppressed with tacrolimus (trough 8 to 12), mycophenolats mofetil (MMF,
1 g/d), and an identical taper of steroids. The analysis compared donor and
recipient ages, mean cold ischemic time, incidence of initial kidney function
(diuresis in the first 24 h) serum creatinine levels, glomerular filtration
rate (GFR), number of dialysis sessions, and rejection rate in the two groups.
RESULTS: Except for the donor and recipient ages (72 vs 54 in donors, and 67
versus 52 years in recipients), no significant differences were observed
between the groups among the rates of acute rejection (6.6% vs 13.2%), delayed
graft function (13.2% required dialysis), or infection (6.6%). Within 1 month
all 45 grafts showed primary function with equal creatinine levels (mean 1.65).
CONCLUSIONS: Calcineurin-free protocols using IL-2 therapy as the initial
suppression allow patients in the “old to old” ET program to display equal
results to cadaveric kidney transplants with initial treatment with calcineurin
antagonists.
----------------------------------------------------
[90]
TÍTULO / TITLE: - Antiproliferative
prostaglandins and the MRP/GS-X pump role in cancer immunosuppression and
insight into new strategies in cancer gene therapy.
REVISTA
/ JOURNAL: - Biochem Pharmacol 2001 Oct 1;62(7):811-9.
AUTORES
/ AUTHORS: - Homem de Bittencourt PI Jr; Curi R
INSTITUCIÓN
/ INSTITUTION: - Department of Physiology, Institute of
Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Sarmento
Leite 500, 90050-170, Porto Alegre, RS, Brazil. pauloivo@vortex.ufrgs.br
RESUMEN
/ SUMMARY: - A dramatic complication in late-stage
cancer patients is host immunosuppression. Cyclopentenone prostaglandins
(CP-PGs) overproduced in cancer may impair the function of the immune system.
These agents, if produced at high concentrations, are powerful cytostatic and
cytotoxic compounds that may arrest cell proliferation and immune response in
cancer. Lymphoid tissues of tumor-bearing animals accumulate large amounts of
CP-PGs, whereas the tumor tissue does not. This may be because cancer cells are
able to overexpress multidrug resistance-associated protein (Mg(2+)-dependent
vanadate-sensitive GS-conjugate export ATPase, MRP/GS-X pump), which extrudes
CP-PGs to the extracellular space as glutathione S-conjugates. In contrast,
MRP/GS-X pump activity is disproportionately low in lymphocytes. This led us to
propose the transfection of lymphocytes with multidrug resistance-associated
protein genes (MRP) for further autologous transfusion or direct in vivo
delivery to lymphocytes by using adenovirus-retrovirus chimeras in order to
restore immune system function in cancer, at least partially. We are currently
evaluating MRP-transfected lymphocyte (MTL) therapy, using Walker 256
tumor-bearing rats as a model. N.
Ref:: 49
----------------------------------------------------
[91]
TÍTULO / TITLE: - Cytokine and
anti-cytokine therapies for inflammatory bowel disease.
REVISTA
/ JOURNAL: - Curr Pharm Des 2003;9(14):1107-13.
AUTORES
/ AUTHORS: - Ogata H; Hibi T
INSTITUCIÓN
/ INSTITUTION: - Department of Internal Medicine, Keio
University School of Medicine, Tokyo, Japan.
RESUMEN
/ SUMMARY: - Although the pathogenesis of inflammatory
bowel disease (IBD) remains elusive, it appears that there is chronic
activation of the immune and inflammatory cascade in genetically susceptible
individuals. Current disease management guidelines have therefore focused on
the use of anti-inflammatory agents, aminosalicylates and corticosteroids.
These conventional therapies continue to be a first choice in the management of
IBD. Immunomodulators, such as azathioprine, 6-mercaptopurine, methotrexate or
cyclosporin, are demonstrating increasing importance against steroid-resistant
and steroid-dependent patients. However, some patients are still refractory to
these therapies. Recent advances in the understanding of the pathophysiological
conditions of IBD have provided new immune system modulators as therapeutic
tools. Other immunosuppressive agents including FK506 and thalidomide have
expanded the choice of medical therapies available for certain subgroups of
patients. Furthermore, biological therapies have begun to assume a prominent
role. Studies with chimeric monoclonal anti-TNF-alpha antibody treatment have
been reported with dramatic successes. However, observations in larger numbers
of treated patients are needed to explicate fully the safety of or risks posed
by this agent such as developing lymphoma, or other malignancies. Another
anti-inflammatory cytokine-therapy includes anti anti-IL-6R, anti-IL-12 or
toxin-conjugated anti IL-7R, recombinant cytokines (IL-10 or IL-11). Given the
diversity of proinflammatory products under its control, NF-kappaB may be
viewed as a master switch in lymphocytes and macrophages, regulating
inflammation and immunity. Although some of them still need more confirmatory
studies, those immune therapies will provide new insights into cell-based and
gene-based treatment against IBD in near future. N. Ref:: 46
----------------------------------------------------
[92]
TÍTULO / TITLE: - Conventional treatment
of Crohn’s disease: objectives and outcomes.
REVISTA
/ JOURNAL: - Inflamm Bowel Dis 2001 May;7 Suppl 1:S2-8.
AUTORES
/ AUTHORS: - Rutgeerts PJ
INSTITUCIÓN
/ INSTITUTION: - Inflammatory Bowel Disease Unit,
University of Leuven, Belgium.
RESUMEN
/ SUMMARY: - Despite conventional medical and/or
surgical intervention, endoscopic and symptomatic relapse is common among
individuals with Crohn’s disease (CD). Treatment goals have therefore been
refocused to include achieving control of active disease and maintaining
remission with agents associated with a minimum of toxic adverse effects.
Conventional treatment regimens have been used with varying success in regard
to these therapeutic goals. Traditionally, aminosalicylates have been
considered effective in inducing a response in some patients with
mild-to-moderate CD but have demonstrated little or no long-term benefit in
controlled clinical trials. Glucocorticosteroid therapy is associated with
higher rates of response in patients with active CD; however, clinical benefits
are frequently offset by the common occurrence of corticosteroid-related
toxicity. Oral controlled-release budesonide has demonstrated comparable
efficacy to prednisolone with less risk for adverse effects, although many
questions remain regarding the long-term use of this agent. Response to
standard immunosuppressive agents such as azathioprine and 6-mercaptopurine in
patients with active disease may require 3 to 6 months from initiation of
treatment. These agents are therefore considered most valuable as maintenance
therapy, providing consistent long-term benefit in patients with chronic
refractory or corticosteroid-dependent disease. Although the incidence of
allergic adverse effects is relatively low with azathioprine/6-mercaptopurine,
more serious adverse effects, including bone marrow suppression,
hepatotoxicity, pancreatitis, and infectious complications, can occur. Limited
success in the treatment of perianal disease has been achieved with antibiotics
such as metronidazole and the immunosuppressives cyclosporine and
azathioprine/6-mercaptopurine. Although broader use of immunosuppressive agents
has allowed improvement in the maintenance of remission in patients with CD,
long-term safety data with these agents are lacking, concerns about toxicity
and the potential risk for neoplasia remain, and attenuation of response with
chronic immunosuppressive use can occur. Therefore, innovative therapeutic
approaches are needed to meet key treatment goals often not addressed by
conventional therapies. N.
Ref:: 48
----------------------------------------------------
[93]
TÍTULO / TITLE: - Treatment of psoriasis.
Part 2. Systemic therapies.
REVISTA
/ JOURNAL: - J Am Acad Dermatol 2001 Nov;45(5):649-61;
quiz 662-4.
AUTORES
/ AUTHORS: - Lebwohl M; Ali S
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology, The Mount Sinai
School of Medicine of New York University, One Gustave L. Levy Place, New York,
NY 10029, USA. mark.lebwohl@mssm.edu
RESUMEN
/ SUMMARY: - The array of systemic medications used in
the treatment of psoriasis is rapidly expanding. In the United States,
methotrexate, retinoids, and cyclosporine are the only systemic drugs approved
by the Food and Drug Administration for the treatment of psoriasis. Monitoring
and dosage recommendations for these medications are reviewed. Other drugs that
are currently available include tacrolimus, mycophenolate mofetil, hydroxyurea,
6-thioguanine, and sulfasalazine. Experience with these drugs is summarized,
and dosage and monitoring recommendations in published literature are
presented. Combinations of different treatments are addressed and
investigational therapies that are in development are reviewed. N. Ref:: 93
----------------------------------------------------
[94]
TÍTULO / TITLE: - Introduction and
overview: recent advances in the immunotherapy of inflammatory bowel disease.
REVISTA
/ JOURNAL: - J Gastroenterol 2003 Mar;38 Suppl
15:36-42.
AUTORES
/ AUTHORS: - Hibi T; Inoue N; Ogata H; Naganuma M
INSTITUCIÓN
/ INSTITUTION: - Department of Internal Medicine, Keio
University School of Medicine, Center for the Research of Inflammatory Bowel
Disease, Keio University School of Medicine, Tokyo, Japan.
RESUMEN
/ SUMMARY: - Ulcerative colitis (UC) and Crohn’s
disease (CD) comprise a series of inflammatory bowel disease (IBD) resulting
from chronic upregulation of the mucosal immune system. Although the
pathogenesis of IBD remains elusive, it appears that there is chronic
activation of the immune and inflammatory cascade in genetically susceptible
individuals. Current disease management guidelines have therefore focused on
the use of antiinflammatory agents, aminosalicylates and corticosteroids.
However, some patients are still refractory to these therapies. Recent advances
in the understanding of the pathophysiological conditions of IBD have provided
new immune system modulators as therapeutic tools. Cytapheresis has
demonstrated effectiveness against UC and has practical use in Japan.
Immunosuppressive agents including cyclosporin A and tacrolimus (FK506) have
expanded the choice of medical therapies available for certain subgroups of
patients. Furthermore, biological therapies have begun to assume a prominent
role. Studies with chimeric monoclonal anti-TNF-alpha antibody treatment of CD
have been reported with dramatic success. Another antiinflammatory cytokine
therapy includes anti-IL-6 receptor, anti-IL-12, or toxin-conjugated anti-IL-7
receptor. Given the diversity of proinflammatory products under its control,
NF-kappa B may be viewed as a master switch in lymphocytes and macrophages,
regulating inflammation and immunity. In the murine 2,4,6-trinitrobenzen
sulfonic acid (TNBS) colitis model, an antisense oligonucleotide to NF-kappa B
p65 ameliorated inflammation even after induction of colitis. Recently, a
clinical pilot trial of this agent demonstrated promising results. Accumulating
evidence suggests that luminal bacterial flora is a requisite and central
factor in the development of IBD. Probiotic therapies such as a nonpathogenic
Escherichia coli strain have been well tolerated, but larger clinical trials
are needed. In addition, novel therapeutic strategies targeting adhesion
molecules and costimulatory molecules, or enhancing tissue repair, are under
investigation. Although some still need more confirmatory studies, these immune
therapies will provide new insights into cell-based and gene-based treatment
against IBD in the near future. N.
Ref:: 36
----------------------------------------------------
[95]
TÍTULO / TITLE: - Potassium channels in T
lymphocytes: toxins to therapeutic immunosuppressants.
REVISTA
/ JOURNAL: - Toxicon 2001 Sep;39(9):1269-76.
AUTORES
/ AUTHORS: - George Chandy K; Cahalan M; Pennington M;
Norton RS; Wulff H; Gutman GA
INSTITUCIÓN
/ INSTITUTION: - Department of Physiology and Biophysics,
University of California Irvine, Room 291, John Irvine Smith Hall, Medical
School, Irvine, CA92697, USA. gchandy@uci.edu N. Ref:: 60
----------------------------------------------------
[96]
TÍTULO / TITLE: - Graft vascular function
after transplantation of pancreatic islets.
REVISTA
/ JOURNAL: - Diabetologia 2002 Jun;45(6):749-63. Epub
2002 May 15.
●●
Enlace al texto completo (gratuito o de pago) 1007/s00125-002-0827-4
AUTORES
/ AUTHORS: - Jansson L; Carlsson PO
INSTITUCIÓN
/ INSTITUTION: - Department of Medical Cell Biology,
Biomedical Center, Uppsala University, Box 571, 751 23 Uppsala, Sweden. Leif.Jansson@medcellbiol.uu.se
RESUMEN
/ SUMMARY: - Endogenous pancreatic islets have a dense
glomerular-like angioarchitecture, which ensures an optimal delivery of oxygen
and nutrients to the islet cells, provides signals from other cells in the body
and disposes secreted hormones. Transplantation of isolated islets means that
their vascular connection is interrupted. The islet grafts therefore depend upon
endothelial cells and microvessels originating in the implantation organ for
derivation of a new vascular system. A re-establishment of islet blood-flow
occurs within 7-14 days after transplantation, mainly through vascular
sprouting. The newly formed blood vessels acquire the morphological
characteristics of those in endogenous islets. In intraportally transplanted
islets to the liver, the islets become revascularized almost exclusively from
tributaries to the hepatic artery. Exocrine contamination of the transplanted
islets could hamper the revascularization process, whereas neither
cryopreservation nor immunosuppressive drugs like cyclosporin, prednisolon and
RS-61443 have any essential effects on the angiogenesis. Investigators have
noticed improvements in islet graft survival and function by means of basic
fibroblast growth factor (bFGF), acidic FGF and endothelial cell growth factor
exposure of the grafts. The functional properties of transplanted islets are
largely unknown, but evidence from experimental islet transplantation suggests
that both the blood perfusion and the tissue oxygen tension of the grafted
islets are chronically decreased, indicating an insufficient vascular system.
In order to achieve optimal condition for survival and function of transplanted
beta cells, it is important to ascertain whether impairments in vascular
function are present also after clinical islet transplantations as well. N. Ref:: 181
----------------------------------------------------
[97]
TÍTULO / TITLE: - Targeted cancer therapy
and immunosuppression using radiolabeled monoclonal antibodies.
REVISTA
/ JOURNAL: - Semin Oncol 2004 Feb;31(1):68-82.
AUTORES
/ AUTHORS: - Bethge WA; Sandmaier BM
INSTITUCIÓN
/ INSTITUTION: - Clinical Research Division, Fred Hutchinson
Cancer Research Center, Seattle, WA 98109, USA.
RESUMEN
/ SUMMARY: - Radioimmunotherapy (RIT) as a means to
target radiation therapy to tumor cells or to specifically suppress host
immunity specifically in the setting of allogeneic transplantation is a
promising new strategy in the armory of today’s oncologist. Different
approaches of RIT such as injection of a stable radioimmunoconjugate or the use
of pretargeting are available. The choice of the radionuclide used for RIT
depends on its radiation characteristics with respect to the malignancy or
cells targeted. beta-Emitters with their lower energy and longer path length
are more suitable for targeting bulky, solid tumors, whereas alpha-emitters
with their high linear energy transfer and short path length are better suited
to target cells or tumors of the hematologic system. Encouraging results have
been obtained using these approaches treating patients with hematologic
malignancies. While the results in solid tumors are somewhat less favorable,
new strategies for patients with minimal residual disease (MRD), using adjuvant
and locoregional treatment, are currently being investigated. In this report,
we outline basic principles of RIT, give an overview of available
radioimmunoconjugates and their clinical applications with special emphasis on
their use in hematologic malignancies, including use in conditioning regimens
for stem cell transplantation (SCT). N.
Ref:: 99
----------------------------------------------------
[98]
TÍTULO / TITLE: - Is there still a role
for cyclosporine in the treatment of inflammatory bowel disease? Pro argument.
REVISTA
/ JOURNAL: - Inflamm Bowel Dis 2003 May;9(3):194-7;
discussion 202-4.
AUTORES
/ AUTHORS: - Kornbluth A
INSTITUCIÓN
/ INSTITUTION: - The Mount Sinai Medical Center, New York,
New York, USA. akornbluth@aol.com N. Ref:: 32
----------------------------------------------------
[99]
TÍTULO / TITLE: - Is there still a role
for cyclosporine in the treatment of inflammatory bowel disease? Con argument.
REVISTA
/ JOURNAL: - Inflamm Bowel Dis 2003 May;9(3):198-201;
discussion 202-4.
AUTORES
/ AUTHORS: - Fellermann K; Luhmann D; Stange EF
INSTITUCIÓN
/ INSTITUTION: - Department of Internal Medicine I,
Robert-Bosch-Krankenhaus, Stuttgart, Germany. klaus.fellermann@rbk.de N. Ref:: 21
----------------------------------------------------
[100]
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
----------------------------------------------------
[101]
TÍTULO / TITLE: - Pimecrolimus cream 1%:
a new development in nonsteroid topical treatment of inflammatory skin
diseases.
REVISTA
/ JOURNAL: - Semin Cutan Med Surg 2001 Dec;20(4):260-7.
AUTORES
/ AUTHORS: - Hebert AA; Warken KA; Cherill R
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology, The University
of Texas Medical School, Houston, USA.
RESUMEN
/ SUMMARY: - Atopic dermatitis (AD) is one of a family
of inflammatory skin diseases (psoriasis, irritant contact dermatitis, and
allergic contact dermatitis). Dermal inflammation and production of
proinflammatory cytokines by activated T cells is a prominent and defining
characteristic in all of these conditions. Corticosteroids, though effective
and potent immunosuppressants, are associated with a number of systemic and
local adverse effects. The ascomycin derivative pimecrolimus (formerly ASM 981)
is a nonsteroid with topical anti-inflammatory activity. Pimecrolimus cream 1%
is minimally absorbed into the circulation; thus, it has a low
bioavailability-reducing the risk for systemic adverse effects. The efficacy
and safety of pimecrolimus cream 1% has been well shown in diverse patient
populations with inflammatory skin diseases in several well-controlled trials.
Significant and rapid amelioration of the signs and symptoms of AD was
established in 3 studies lasting 6 weeks each, evaluating 589 pediatric
patients. In a 1-year study, pimecrolimus was applied at the first signs and
symptoms of eczema to prevent the progression of AD to flares. Flares were
prevented in over 50% of patients who used pimecrolimus cream 1%, reducing or
completely eliminating the need for topical corticosteroids during a 1-year
treatment period. Results in pimecrolimus studies in chronic irritant hand
dermatitis and chronic hand dermatitis of mixed causes indicate potential for
use in these important diseases, and further study in these indications is
warranted. N. Ref:: 32
----------------------------------------------------
[102]
TÍTULO / TITLE: - Hepatitis C virus
infection and vasculitis: implications of antiviral and immunosuppressive
therapies.
REVISTA
/ JOURNAL: - Arthritis Rheum 2002 Mar;46(3):585-97.
●●
Enlace al texto completo (gratuito o de pago) 1002/art.10107 [pii
●●
Enlace al texto completo (gratuito o de pago) 1002/art.10107
AUTORES
/ AUTHORS: - Vassilopoulos D; Calabrese LH
INSTITUCIÓN
/ INSTITUTION: - Hippokration General Hospital, Athens
University, Athens, Greece. N.
Ref:: 92
----------------------------------------------------
[103]
TÍTULO / TITLE: - Interactions between
cyclosporin and lipid-lowering drugs: implications for organ transplant
recipients.
REVISTA
/ JOURNAL: - Drugs 2003;63(4):367-78.
AUTORES
/ AUTHORS: - Asberg A
INSTITUCIÓN
/ INSTITUTION: - Laboratory for Renal Physiology, Section
of Nephrology, Medical Department, The National Hospital, Oslo, Norway. anderas@klinmed.uio.no
RESUMEN
/ SUMMARY: - Dyslipidaemia is more frequent in solid
organ transplant recipients than in the general population, primarily as a
result of immunosuppressive drug treatment. Both cyclosporin and
corticosteroids are associated with dyslipidaemic adverse effects. In order to
reduce the overall cardiovascular risk in these patients, lipid-lowering drugs
have become widely used, especially HMG-CoA reductase inhibitors (statins).
Cyclosporin, as well as most statins (lovastatin, simvastatin, atorvastatin and
pravastatin) are metabolised by cytochrome P450 (CYP)3A4, so a bilateral pharmacokinetic
interaction between these drugs is theoretically possible. However, results
from several studies show that statins do not induce increased systemic
exposure of cyclosporin. A small (but not clinically relevant) reduction in
systemic exposure of cyclosporin has actually been shown in many studies.
Cyclosporin-treated patients on the other hand show several-fold higher
systemic exposure of all statins, both those that are metabolised by CYP3A4 and
fluvastatin (metabolised by CYP2C9). Therefore, the mechanism for this
interaction does not seem to be solely caused by inhibition of CYP3A4
metabolism, but it is probably also a result of inhibition of statin-transport
in the liver, at least in part. Other lipid-lowering drugs, such as fibric acid
derivatives, bile acid sequestrants, probucol, fish oils and orlistat are also
used in solid organ transplant recipients. Most of them do not interact with
cyclosporin, but there are reports indicating that both probucol and orlistat
may reduce cyclosporin bioavailablility to a clinically relevant degree. There
is no information on possible interaction effects of cyclosporin on the
pharmacokinetics of lipid-lowering drugs other than statins, but it is not
likely that any clinical relevant interference exists with fish oil, orlistat,
probucol or bile acid sequestrants. N.
Ref:: 71
----------------------------------------------------
[104]
TÍTULO / TITLE: - European best practice
guidelines for renal transplantation. Section IV: Long-term management of the
transplant recipient. IV.3.1 Long-term immunosuppression. Late steroid or
cyclosporine withdrawal.
REVISTA
/ JOURNAL: - Nephrol Dial Transplant. Acceso gratuito
al texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://ndt.oupjournals.org/
●●
Cita: Nephrology Dialysis Transplantation: <> 2002;17 Suppl 4:19-20.
RESUMEN
/ SUMMARY: - GUIDELINES: A. In order to reduce or avoid
long-term serious adverse effects of corticosteroids, such as bone fractures,
diabetes mellitus, arterial hypertension, osteoporosis and eye complications,
steroid withdrawal should be considered. B. Steroid withdrawal is safe only in
a proportion of graft recipients and is recommended only in low-risk patients.
The efficacy of the remaining immunosuppression should be considered. C. After
steroid withdrawal, graft function has to be monitored very carefully because
of the risk of a delayed but continuous loss of function due to chronic graft
dysfunction. In the case of functional deterioration or dysfunction, steroids
should be re-administered. D. Cyclosporine withdrawal might be considered in
order to ameliorate nephrotoxicity, arterial hypertension, lipid disorders and
hypertrichosis. This can be carried out with no significant long-term risk of
progressive graft loss. The efficacy of the remaining immunosuppression should
be considered. After cyclosporine withdrawal, careful monitoring for acute
rejection is recommended.
----------------------------------------------------
[105]
TÍTULO / TITLE: - Medical treatment of
primary biliary cirrhosis and primary sclerosing cholangitis.
REVISTA
/ JOURNAL: - Digestion 2001;64(3):137-50.
AUTORES
/ AUTHORS: - Holtmeier J; Leuschner U
INSTITUCIÓN
/ INSTITUTION: - Medizinische Klinik II, Johann Wolfgang
Goethe-Universitat, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany.
RESUMEN
/ SUMMARY: - Treatment of primary biliary cirrhosis
(PBC) and primary sclerosing cholangitis (PSC) with ursodeoxycholic acid (UDCA)
has been in common use since 1985. In PBC, treatment with UDCA improves
laboratory data, liver histology, enables a longer transplantation-free
interval and prolongs disease survival. Because UDCA is unable to cure the
disease newer drugs or combination therapies are still needed. Studies with
UDCA and immunosuppressants such as prednisone, budesonide and azathioprine
have shown that in selected patients combination therapy may be superior to
UDCA monotherapy. PSC is treated successfully with UDCA and endoscopic
dilatation of the bile duct strictures. Treatment of extrahepatic
manifestations of cholestatic liver disease such as pruritus, fatigue,
osteoporosis and steatorrhea can be problematic and time-consuming. N. Ref:: 186
----------------------------------------------------
[106]
TÍTULO / TITLE: - Fluorescence
polarization detection for affinity capillary electrophoresis.
REVISTA
/ JOURNAL: - Electrophoresis 2002 Mar;23(6):903-8.
●●
Enlace al texto completo (gratuito o de pago) 1002/1522-2683(200203)23:6<903::AID-ELPS903>3.0.CO;2-2
[pii]
AUTORES
/ AUTHORS: - Le XC; Wan QH; Lam MT
INSTITUCIÓN
/ INSTITUTION: - Environmental Health Sciences Program,
Department of Public Health Sciences, Faculty of Medicine, University of
Alberta, Edmonton, Alberta T6G 2G3, Canada. xc.le@ualberta.ca
RESUMEN
/ SUMMARY: - Affinity capillary electrophoresis (ACE)
with laser-induced fluorescence polarization (LIFP) detection is described,
with examples of affinity interaction studies. Because fluorescence
polarization is sensitive to changes in the rotational motion arising from
molecular association or dissociation, ACE-LIFP is capable of providing
information on the formation of affinity complexes prior to or during CE
separation. Unbound, small fluorescent probes generally have little
fluorescence polarization because of rapid rotation of the molecule in
solution. When the small fluorescent probe is bound to a larger affinity agent,
such as an antibody, the fluorescence polarization (and anisotropy) increases
due to slower motion of the much larger complex molecule in the solution.
Fluorescence polarization results are obtained by simultaneously measuring
fluorescence intensities of vertical and horizontal polarization planes.
Applications of CE-LIFP to both strong and weak binding systems are discussed
with antibody-antigen and DNA-protein binding as examples. For strong affinity
binding, such as between cyclosporine and its antibody, complexes are formed
prior to CE-LIFP analysis. For weaker binding, such as between single-stranded
DNA and its binding protein, the single-stranded DNA binding protein is added
to the CE separation buffer to enhance dynamic formation of affinity complexes.
Both fluorescence polarization (and anisotropy) and mobility shift results are
complementary and are useful for immunoassays and binding studies. N. Ref:: 25
----------------------------------------------------
[107]
TÍTULO / TITLE: - Review article: medical
treatment of severe ulcerative colitis.
REVISTA
/ JOURNAL: - Aliment Pharmacol Ther 2003 Jun;17 Suppl
2:7-10.
AUTORES
/ AUTHORS: - Rizzello F; Gionchetti P; Venturi A;
Campieri M
INSTITUCIÓN
/ INSTITUTION: - Department of Internal Medicine and
Gastroenterology, University of Bologna, Italy.
RESUMEN
/ SUMMARY: - Severe colitis is a life-threatening
complication of ulcerative colitis. Early recognition of the severity of the
colitis and intensive treatment and monitoring have all contributed to improved
outcome. Since their introduction in 1950s, corticosteroids are the first line
therapy for severe active ulcerative colitis (UC). Several prognostic
parameters (such as stools movement per day, C-reactive protein, increased
amount of intestinal gas or small bowel dilation, hypoalbuminemia, fever etc)
help the physician to quickly introduce cyclosporin or to refer the patient to
the surgeon. This decision requires a careful evaluation of the patient and a
medical /surgical team. Infliximab seems to be a promising drug but more
controlled trial are needed. N.
Ref:: 21
----------------------------------------------------
[108]
TÍTULO / TITLE: - Steroid-resistant
kidney transplant rejection: diagnosis and treatment.
REVISTA
/ JOURNAL: - J Am Soc Nephrol. Acceso gratuito al texto
completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.jasn.org/
●●
Cita: Journal of the American Society of Nephrology: <> 2001 Feb;12 Suppl
17:S48-52.
AUTORES
/ AUTHORS: - Bock HA
INSTITUCIÓN
/ INSTITUTION: - Division of Nephrology, Kantonsspital,
Aarau, Switzerland. bock@ksa.ch
RESUMEN
/ SUMMARY: - Decreases in transplant function may be
attributable to a variety of conditions, including prerenal and postrenal
failure, cyclosporin A (CsA) toxicity, polyoma nephritis, recurrent glomerulonephritis,
and rejection. The diagnosis of rejection should therefore be made on the basis
of a transplant biopsy of adequate size, before the initiation of any therapy.
Pulse steroid treatment (three to five 0.25- to 1.0-g pulses of
methylprednisolone, administered intravenously) is the usual first-line therapy
and has a 60 to 70% success rate, although orally administered prednisone (0.25
g) may be just as efficacious. Even if reverted, any rejection should trigger
an at least temporary increase in basal immunosuppression, consisting of an
increase in CsA or tacrolimus target levels, the addition of steroids or an
increase in their dosage, the addition of mycophenolate mofetil, or a switch
from CsA to tacrolimus. The addition of rapamycin or its RAD derivative may
fulfill the same purpose. Steroid resistance should not be assumed before the
fifth day of pulse steroid treatment, although histologic features of vascular
rejection may indicate the need for more aggressive treatment earlier.
Steroid-resistant rejection is traditionally treated with poly- or monoclonal
antilymphocytic antibodies, with success rates of 60 to 70%. Their potential
benefit must be carefully balanced against the risks of infection and lymphoma.
More recently, mycophenolate mofetil has been successfully used to treat
steroid-resistant rejection, but only of the interstitial (cellular) type.
Switching from CsA to tacrolimus for treating recurrent or antibody-resistant
rejection is successful in approximately 60% of cases. Plasmapheresis and
intravenously administered Ig have been used in some desperate cases, with
surprising success. Because none of the available drugs has a significantly
better profile of therapeutic versus adverse effects, the possible benefits of
continued rejection therapy must be continuously balanced with the potential
for serious, sometimes fatal, side effects.
N. Ref:: 35
----------------------------------------------------
[109]
TÍTULO / TITLE: - A novel pathway
regulating the mammalian target of rapamycin (mTOR) signaling.
REVISTA
/ JOURNAL: - Biochem Pharmacol 2002 Oct 1;64(7):1071-7.
AUTORES
/ AUTHORS: - Chen J; Fang Y
INSTITUCIÓN
/ INSTITUTION: - Department of Cell and Structural Biology,
University of Illinois at Urbana-Champaign, 601 South Goodwin Avenue, B107,
Urbana, IL 61801, USA. jiechen@uiuc.edu
RESUMEN
/ SUMMARY: - Originally discovered as an anti-fungal
agent, the bacterial macrolide rapamycin is a potent immunosuppressant and a
promising anti-cancer drug. In complex with its cellular receptor, the
FK506-binding protein (FKBP12), rapamycin binds and inhibits the function of
the mammalian target of rapamycin (mTOR). By mediating amino acid sufficiency,
mTOR governs signaling to translational regulation and other cellular functions
by converging with the phosphatidylinositol 3-kinase (PI3K) pathway on
downstream effectors. Whether mTOR receives mitogenic signals in addition to
nutrient-sensing has been an unresolved issue, and the mechanism of action of
rapamycin remained unknown. Our recent findings have revealed a novel link
between mitogenic signals and mTOR via the lipid second messenger phosphatidic
acid (PA), and suggested a role for mTOR in the integration of nutrient and
mitogen signals. A molecular mechanism for rapamycin inhibition of mTOR
signaling is proposed, in which a putative interaction between PA and mTOR is
abolished by rapamycin binding. Collective evidence further implicates the
regulation of the rapamycin-sensitive signaling circuitry by phospholipase D,
and potentially by other upstream regulators such as the conventional protein
kinase C, the Rho and ARF families of small G proteins, and calcium ions. As
the mTOR pathway has been demonstrated to be an important anti-cancer target,
the identification of new components and novel regulatory modes in mTOR
signaling will facilitate the future development of diagnostic and therapeutic
strategies. N. Ref:: 67
----------------------------------------------------
[110]
TÍTULO / TITLE: - ATP-binding cassette
transporters and calcineurin inhibitors: potential clinical implications.
REVISTA
/ JOURNAL: - Transplant Proc 2001 May;33(3):2420-1.
AUTORES
/ AUTHORS: - van Gelder T; Klupp J; Sawamoto T;
Christians U; Morris RE
INSTITUCIÓN
/ INSTITUTION: - Department of Internal Medicine (T.vG.),
University Hospital Rotterdam, Rotterdam, The Netherlands. vangelder@INW1.AZR.NL N. Ref:: 17
----------------------------------------------------
[111]
TÍTULO / TITLE: - Current status of liver
transplantation in children.
REVISTA
/ JOURNAL: - Pediatr Clin North Am 2003
Dec;50(6):1335-74.
AUTORES
/ AUTHORS: - McDiarmid SV
INSTITUCIÓN
/ INSTITUTION: - Division of Gastroenterology, Hepatology,
and Nutrition, David Geffen School of Medicine, University of California, Los
Angeles, Medical Center, 10833 Le Conte Avenue, Los Angeles, CA 90095-1752,
USA. smcdiarmid@mednet.ucla.edu
RESUMEN
/ SUMMARY: - There are two critical issues on opposite
ends of the timeline for patients who are eligible for liver transplantation.
On the one hand, the crisis in the cadaveric organ supply makes surviving to
transplant ever more risky. On the other hand, patients who receive successful
transplants face the consequences of long-term immunosuppression and its
potentially life-threatening complications. The donor shortage is forcing
difficult decisions that affect all patients who await liver transplantation.
It is important to scrutinize carefully the results of all policies that govern
allocation and the ethics of the solutions we advocate to ensure that no
patient subgroup is being at a disadvantage. Current immunosuppression
practices are being challenged by an increasing understanding of the
immunologic events triggered by the allograft and the goal to free patients
from consequences of a lifetime of immunosuppression. Clinicians can expect,
and perhaps require, that new immunosuppressive protocols will address how the
planned intervention might be expected to advance the understanding of
tolerance mechanisms. As knowledge increases, clinicians can anticipate
innovative new immunosuppressive proposals. Calcineurin and steroid-free
induction, the use of donor-derived bone marrow infusion, recipient
pretreatment, costimulatory blockade, and new antibody induction approaches are
all being proposed—often in combination—for clinical trials. Researchers face
additional challenges in defining endpoints if the goal is not just the
short-term reduction in rejection but the minimization, and eventual
discontinuation, of immunosuppressive drugs while maintaining excellent
long-term graft function. How much “failure” will be accepted and how will it
be defined? How will clinicians interpret liver biopsies if they begin to
accept that some lymphocytic infiltrates may be beneficial mediators of the
ongoing immune activation necessary for the maintenance of tolerance? How will
they adjust immunosuppression practices to the dynamic processes in the immune
response that maintain tolerance? Remarkable short-term successes in providing
transplants for thousands of children with liver failure have brought these
challenges into sharp focus. Clinicians must seek to move the life-giving
science of transplantation toward a new goal: providing long lifetimes of
excellent graft function with minimal toxicity from immunosuppressive drugs and
the hope of freedom from immunosuppression altogether. Pediatric liver
recipients, whose grafts have inherent tolerogenic potential and for whom we
can anticipate decades of life after transplant, may prove to be an ideal study
population to further these goals. N.
Ref:: 266
----------------------------------------------------
[112]
TÍTULO / TITLE: - Pimecrolimus: a review
of pre-clinical and clinical data.
REVISTA
/ JOURNAL: - Int J Clin Pract 2003 May;57(4):319-27.
AUTORES
/ AUTHORS: - Graham-Brown RA; Grassberger M
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology, Leicester Royal
Infirmary, Leicester LEI 5WW, UK.
RESUMEN
/ SUMMARY: - Pimecrolimus (Elidel) is a novel
cell-selective inhibitor of inflammatory cytokines that has specifically been
developed for the treatment of inflammatory skin diseases due to its favourable
skin selective pharmacological profile. Therapeutic efficacy and safety of
pimecrolimus cream 1% has been established in the short-term treatment and the
long-term management of atopic eczema in clinical studies in adults, children
and infants. It rapidly relieves pruritus, and redness and swelling disappear
or are only mild in up to 70% of pimecrolimus treated patients during the first
three weeks. When applied at the first signs and symptoms of atopic eczema,
pimecrolimus has proven to prevent flare progression and to provide superior
long-term disease control compared with a conventional treatment, based on
reactive use of corticosteroids. Pimecrolimus cream 1% is well tolerated, even
on sensitive areas such as the face and neck. Blood concentrations remain low,
even when extensive body areas are treated and no clinically significant
systemic effects have been observed during short- or long-term clinical studies
with pimecrolimus. N.
Ref:: 47
----------------------------------------------------
[113]
TÍTULO / TITLE: - Immunosuppression and
transplant vascular disease: benefits and adverse effects.
REVISTA
/ JOURNAL: - Pharmacol Ther 2003 Nov;100(2):141-56.
AUTORES
/ AUTHORS: - Moien-Afshari F; McManus BM; Laher I
INSTITUCIÓN
/ INSTITUTION: - Department of Pharmacology and
Therapeutics, Faculty of Medicine, University of British Columbia, 2176 Health
Sciences Mall, Vancouver, BC Canada V6T 1Z3.
RESUMEN
/ SUMMARY: - Cardiac allograft vasculopathy (CAV)
occurs within 5 years of transplantation surgery and represents the main cause
of death in long-term heart transplant survivors. The detailed pathogenesis of
CAV is unknown, but there are strong indications that immunologic mechanisms,
which are regulated by nonimmunologic factors, are the major cause of this
phenomenon. Cyclosporine A (CsA) is a frequently used immunosuppressive agent
in transplant medicine to prevent rejection. The mechanism of action of CsA
involves initial binding to cyclophilin to form a complex that then inhibits
calcineurin (CN), leading to reduced interleukin (IL)-2 production as part of
the signal transduction pathway for the activation of B-lymphocytes and
T-lymphocytes. Based on this proposed mechanism, it was expected that CsA
should be an effective strategy in attenuating the host immune response against
transplanted allograft tissue; however, CsA has not changed the outcome of CAV.
Several mechanisms have been suggested for the ineffectiveness of CsA in
long-term prevention of CAV. For example, routine therapeutic doses of CsA may
block CN incompletely (50%), whereas complete blockade requires doses that are
not clinically tolerable. Another explanation is the possible activation of
T-cell receptors directly (CN independent) by the immune response, which
induces protein kinase C theta (PKCtheta) and leads to IL-2 production and
immune rejection. Moreover, there may be a role for nonimmunologic mechanisms,
such as complement, which cannot be controlled by CsA, or CsA may cause
hypercholesterolemia or induce overexpression of transforming growth
factor-beta (TGF-beta). This review also compares the effect of CsA with other
immunosuppressants in allograft artery preservation and their clinical
efficacy. N. Ref:: 192
----------------------------------------------------
[114]
TÍTULO / TITLE: - Pharmacokinetic,
pharmacodynamic, and outcome investigations as the basis for mycophenolic acid
therapeutic drug monitoring in renal and heart transplant patients.
REVISTA
/ JOURNAL: - Clin Biochem 2001 Feb;34(1):17-22.
AUTORES
/ AUTHORS: - Shaw LM; Korecka M; DeNofrio D; Brayman KL
INSTITUCIÓN
/ INSTITUTION: - Departments of Pathology & Laboratory
Medicine and Surgery, University of Pennsylvania Medical Center, Philadelphia,
PA, USA. shawlmj@mail.med.upenn.edu
RESUMEN
/ SUMMARY: - Mycophenolate mofetil is widely used in
combination with either cyclosporine or tacrolimus for rejection prophylaxis in
renal and heart transplant patients. Although not monitored routinely nearly to
the degree that other agents such as cyclosporine or tacrolimus, there is an
expanding body of experimental evidence for the utility of monitoring
mycophenolic acid, the primary active metabolite of mycophenolate mofetil,
plasma concentration as an index of risk for the development of acute
rejection. The following are important experimentally-based reasons for
recommending the incorporation of target therapeutic concentration monitoring
of mycophenolic acid: (1) the MPA dose-interval
area-under-the-concentration-time curve, and less precisely, MPA predose
concentrations predict the risk for development of acute rejection; (2) the
strong correlation between mycophenolic acid plasma concentrations and
expression of important cell surface activation antigens, whole blood
pharmacodynamic assays of lymphocyte proliferation and median graft rejection
scores in a heart transplant animal model; (3) the greater than 10-fold
interindividual variation of MPA area under the concentration time curve values
in heart and renal transplant patients receiving a fixed dose of the parent drug;
(4) drug-drug interactions involving other immunosuppressives are such that
when switching from one to another (eg, from cyclosporine to tacrolimus or
vice-versa) substantial changes in MPA concentrations can occur in patients
receiving a fixed dose of the parent drug; (5) significant effects of liver and
kidney diseases on the steady-state total and free mycophenolic acid area under
the concentration time curve values; (6) the need to closely monitor
mycophenolic acid when a major change in immunosuppression is planned such as
steroid withdrawal. Current investigations are focused on determination of the
most optimal sampling time and for mycophenolic acid target therapeutic
concentration monitoring. Further investigations are needed to evaluate the pharmacologic
activity of the newly described acyl glucuronide metabolite of mycophenolic
acid which has been shown to inhibit, in vitro, inosine monophosphate
dehydrogenase. N.
Ref:: 37
----------------------------------------------------
[115]
TÍTULO / TITLE: - Alternate treatments in
asthma.
REVISTA
/ JOURNAL: - Chest. Acceso gratuito al texto completo a
partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.chestjournal.org/
●●
Cita: Chest: <> 2003 Apr;123(4):1254-65.
AUTORES
/ AUTHORS: - Niven AS; Argyros G
INSTITUCIÓN
/ INSTITUTION: - Pulmonary/Critical Care Medicine Service,
William Beaumont Army Medical Center, El Paso, TX 79920, USA. Alexander.Niven@amedd.army.mil N. Ref:: 142
----------------------------------------------------
[116]
TÍTULO / TITLE: - International Consensus
Conference on Atopic Dermatitis II (ICCAD II): clinical update and current treatment
strategies.
REVISTA
/ JOURNAL: - Br J Dermatol 2003 May;148 Suppl 63:3-10.
AUTORES
/ AUTHORS: - Ellis C; Luger T; Abeck D; Allen R;
Graham-Brown RA; De Prost Y; Eichenfield LF; Ferrandiz C; Giannetti A; Hanifin
J; Koo JY; Leung D; Lynde C; Ring J; Ruiz-Maldonado R; Saurat JH
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology, University of
Michigan Medical Center, Ann Arbor, MI, U.S.A. cellis@med.umich.edu N. Ref:: 65
----------------------------------------------------
[117]
TÍTULO / TITLE: - Recent developments in
inflammatory bowel disease.
REVISTA
/ JOURNAL: - Med Clin North Am 2002 Nov;86(6):1497-523.
AUTORES
/ AUTHORS: - Su C; Lichtenstein GR
INSTITUCIÓN
/ INSTITUTION: - Division of Gastroenterology, Department
of Medicine, Hospital of the University of Pennsylvania, University of
Pennsylvania School of Medicine, Third Floor Ravdin Building, 3400 Spruce
Street, Philadelphia, PA 19104-4283, USA.
RESUMEN
/ SUMMARY: - The evolving medical armamentarium holds
promise for more precise and effective therapies for IBD. The experience with
anti-TNF therapy, particularly infliximab, illustrates the potential efficacy
of therapies targeted at specific mediators or pathways involved in the
pathogenesis. Advances in molecular technology have enabled the development of
novel and potentially effective targeted therapies. Equally important is the
increasing scientific understanding of the pathogenesis of IBD, which will
likely improve the ability to stratify disease and to select therapies based on
genotypic, immunologic, and phenotypic profiles in the future. N. Ref:: 191
----------------------------------------------------
[118]
TÍTULO / TITLE: - High-dose
immunoablative therapy with hematopoietic stem cell support in the treatment of
severe autoimmune disease: current status and future direction.
REVISTA
/ JOURNAL: - Intern Med 2002 Aug;41(8):608-12.
AUTORES
/ AUTHORS: - Tyndall A; Koike T
INSTITUCIÓN
/ INSTITUTION: - Department of Rheumatology, University of
Basel, Switzerland.
RESUMEN
/ SUMMARY: - In the past 5 years approximately 500
patients worldwide suffering from severe autoimmune disease (AD) have received
an autologous hematopoietic stem cell transplantation (HSCT) as treatment
following high-dose chemotherapy. The EBMT and EULAR data base contains 370
registrations, the most frequently transplanted ADs being multiple sclerosis
(MS), systemic sclerosis (SSc), rheumatoid arthritis (RA), juvenile idiopathic
arthritis (JIA), systemic lupus erythematosus (SLE) and idiopathic
thrombocytopenic purpura (ITP). Around 70% responded initially well, with
durable remission/stabilization seen more frequently in MS and SSc than in RA
and SLE, the latter having around 2/3 relapses, the majority of which respond
to simple agents. Overall 8% transplant-related mortality was seen with large
inter AD differences (12.5% in SSc and only one patient in RA) probably
reflecting the degree of vital organ involvement at the time of transplant.
This phase I/II data has led to a running phase III randomized trial in SSc
called the Autologous Stem cell Transplantation International Scleroderma
(ASTIS) trial, and it will soon begin in MS (ASTIMS) and RA (ASTIRA). The
concept of immunological “re-setting” has evolved, and needs to be confirmed by
longer follow-up and the multicentre, international phase III randomized
studies. N. Ref:: 18
----------------------------------------------------
[119]
- Castellano -
TÍTULO / TITLE:Leucoencefalopatia posterior
reversible en un paciente con linfoma no-Hodgkin tras tratamiento con CHOP.
Reversible posterior leukoencephalopathy in a patient with non-Hodgkin’s
lymphoma after treatment with CHOP.
REVISTA
/ JOURNAL: - An Med Interna 2001 Nov;18(11):591-3.
AUTORES
/ AUTHORS: - Gimenez-Mesa E; Martinez-Salio A;
Porta-Etessam J; Berbel Garcia A; Cedena Romero T; Salama Bendoyan P
INSTITUCIÓN
/ INSTITUTION: - Servicio de Neurologia, Hospital
Universitario Doce de Octubre, Ctra de Andalucia km 5,400, 28041 Madrid.
RESUMEN
/ SUMMARY: - Reversible posterior leukoencephalopathy
syndrome is a newly characterised and increasingly recognized
clinico-radiologic syndrome. Underlying conditions that reportedly trigger this
syndrome include hypertensive encephalopathy, eclampsia, renal failure, and
immunosuppressive drug therapy with cyclosporine, tacrolimus and interferon
alpha. We describe a 51-year-old woman with non-Hodgkin’s lymphoma treated with
conventional CHOP chemotherapy. Eight days after this treatment she developed
severe headache, bilateral visual loss and focal seizures with secondary
generalization. Neurologic examination showed confusion, cortical blindness,
and left hemiparesis with hyperreflexia and sensory loss. A cranial T2-weighted
magnetic resonance imaging revealed increased signal intensity in the occipital
and frontal lobes in both hemispheres and right parietal lobe. A diagnosis of
reversible posterior leukoencephalopathy was made. She presented a favourable
outcome with conservative treatment with mannitol and phenytoin. A new cranial
scanning showed nearly complete resolution of the abnormalities. To the best of
our knowledge, this is the first case of reversible posterior
leukoencephalopathy in a patient treated with standard-dose CHOP. In this
patient, we confirm the theoretical pathophysiologic mechanisms suggested
explaining how these drugs can cause the syndrome. N. Ref:: 7
----------------------------------------------------
[120]
TÍTULO / TITLE: - Mycophenolate mofetil:
new applications for this immunosuppressant.
REVISTA
/ JOURNAL: - Ann Allergy Asthma Immunol 2003
Jan;90(1):15-19; quiz 20, 78.
AUTORES
/ AUTHORS: - Moder KG
INSTITUCIÓN
/ INSTITUTION: - Division of Rheumatology, Mayo Clinic,
Rochester, Minnesota 55905, USA.
RESUMEN
/ SUMMARY: - OBJECTIVES: This article should
familiarize the reader with the pharmacokinetics, mechanisms of action,
potential toxicities, and current and future applications of mycophenolate
mofetil. DATA SOURCES: The current medical literature. RESULTS: Mycophenolate
mofetil is an immunosuppressive agent that has been used for transplant
recipients. More recently, this agent has been used to treat several
inflammatory conditions. CONCLUSIONS: Mycophenolate mofetil has the potential
to be a useful agent in the treatment of several inflammatory conditions,
including systemic lupus erythematosus.
N. Ref:: 39
----------------------------------------------------
[121]
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
----------------------------------------------------
[122]
TÍTULO / TITLE: - Clinical validation
studies of Neoral C(2) monitoring: a review.
REVISTA
/ JOURNAL: - Transplantation 2002 May 15;73(9
Suppl):S3-11.
AUTORES
/ AUTHORS: - Nashan B; Cole E; Levy G; Thervet E
INSTITUCIÓN
/ INSTITUTION: - Klinik fur Viszeral und
Transplantationschirurgie, Medizinische Hochschule Hannover, Carl-Neuberg-Str.
1, D-30625 Hannover, Germany. N.
Ref:: 34
----------------------------------------------------
[123]
TÍTULO / TITLE: - Alloimmunity and nonimmunologic
risk factors in cardiac allograft vasculopathy.
REVISTA
/ JOURNAL: - Eur Heart J 2003 Jul;24(13):1180-8.
AUTORES
/ AUTHORS: - Vassalli G; Gallino A; Weis M; von Scheidt
W; Kappenberger L; von Segesser LK; Goy JJ
INSTITUCIÓN
/ INSTITUTION: - Division of Cardiology, University
Hospital, Lausanne, Switzerland. gvassall@hospvd.ch
RESUMEN
/ SUMMARY: - Graft vasculopathy is an accelerated form
of coronary artery disease that occurs in transplanted hearts. Despite major
advances in immunosuppression, the prevalence of the disease has remained
substantially unchanged during the last two decades. According to the ‘response
to injury’ paradigm, graft vasculopathy is the result of a continuous
inflammatory response to tissue injury initiated by both alloantigen-dependent
and independent stress responses. Experimental evidence suggests that these
responses may become self-sustaining, as allograft re-transplantation into the
donor strain at a later stage fails to prevent disease progression.
Histological evidence of endothelitis and arteritis, in association with intima
fibrosis and atherosclerosis, reflects the central role of alloimmunity and
inflammation in the development of arterial lesions. Experimental results in
gene-targeted mouse models indicate that cellular and humoral immune responses
are both involved in the pathogenesis of graft vasculopathy. Circulating
antibodies against donor endothelium are found in a significant number of
patients, but their pathogenic role is still controversial.
Alloantigen-independent factors include donor-transmitted coronary artery
disease, surgical trauma, ischaemia-reperfusion injury, viral infections,
hyperlipidaemia, hypertension, and glucose intolerance. Recent therapeutic
advances include the use of novel immunosuppressive agents such as sirolimus
(rapamycin), HMG-CoA reductase inhibitors, calcium channel blockers, and
angiotensin converting enzyme inhibitors. Optimal treatment of cardiovascular
risk factors remains of paramount importance.
N. Ref:: 100
----------------------------------------------------
[124]
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
----------------------------------------------------
[125]
TÍTULO / TITLE: - Cyclosporine-associated
hyperkalemia: report of four allogeneic blood stem-cell transplant cases.
REVISTA
/ JOURNAL: - Transplantation 2003 Apr 15;75(7):1069-72.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000057241.69355.59
AUTORES
/ AUTHORS: - Caliskan Y; Kalayoglu-Besisik S; Sargin D;
Ecder T
INSTITUCIÓN
/ INSTITUTION: - Bone Marrow Transplantation Unit,
Department of Internal Medicine, Division of Hematology, Istanbul School of
Medicine, CAPA 34 390, Istanbul, Turkey.
RESUMEN
/ SUMMARY: - BACKGROUND: Nephrotoxicity is a well-known
effect of cyclosporine (CsA) that causes a reduction in glomerular filtration
rate through vasoconstriction of the afferent glomerular arterioles and may
result in acute renal failure. Isolated CsA-induced hyperkalemia occurring
through different mechanisms is also common. However, there are only a few
“case reports” addressing this phenomenon in allogeneic bone marrow
transplantation patients. In this report, we propose mechanisms and methods of
managing CsA-associated hyperkalemia in allogeneic transplantation. METHODS: We
report on four allogeneic blood stem- cell transplant cases and a review of the
literature. RESULTS: Four adult leukemia patients underwent allogeneic
peripheral blood stem cell transplantation and received CsA as a part of their
graft-versus-host disease prophylaxis. The patients developed hyperkalemia,
despite adequate kidney function. CsA seemed to be the only pharmaceutical agent
to which this electrolyte abnormality could be attributed. Renal tubule
dysfunction and secondary hypoaldosteronism seemed to be the reasons for
CsA-associated hyperkalemia. CONCLUSION: This report of four cases demonstrates
that CsA should be considered among the possible causes of hyperkalemia in bone
marrow transplantation. There may be a need for urgent intervention depending
on the severity of hyperkalemia. Monitoring of blood CsA level and dose
adjustment are important for the prevention of this complication. N. Ref:: 22
----------------------------------------------------
[126]
TÍTULO / TITLE: - Effectiveness of
sirolimus-eluting stent implantation for recurrent in-stent restenosis after
brachytherapy.
REVISTA
/ JOURNAL: - Am J Cardiol 2003 Jul 15;92(2):200-3.
AUTORES
/ AUTHORS: - Saia F; Lemos PA; Sianos G; Degertekin M;
Lee CH; Arampatzis CA; Hoye A; Tanabe K; Regar E; van der Giessen WJ; Smits PC;
de Feyter P; Ligthart J; van Domburg RT; Serruys PW
INSTITUCIÓN
/ INSTITUTION: - Erasmus MC, Thoraxcenter, Dr
Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. N. Ref:: 13
----------------------------------------------------
[127]
TÍTULO / TITLE: - Pharmacokinetics of
tacrolimus-based combination therapies.
REVISTA
/ JOURNAL: - Nephrol Dial Transplant. Acceso gratuito
al texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://ndt.oupjournals.org/
●●
Cita: Nephrology Dialysis Transplantation: <> 2003 May;18 Suppl 1:i12-5.
AUTORES
/ AUTHORS: - Undre NA
INSTITUCIÓN
/ INSTITUTION: - Fujisawa GmbH, Neumarkter Str. 61, D-81673
Munich, Germany. nas.undre@fujisawa.de
RESUMEN
/ SUMMARY: - This paper reviews the pharmacokinetics of
tacrolimus, with special reference to its combination with adjunctive
immunosuppressants. Oral bioavailability of tacrolimus, which is variable
between patients, averages approximately 25%. This is largely due to extrahepatic
metabolism of tacrolimus in the gastrointestinal epithelium. Nevertheless,
intra-patient variability is low, as evidenced by the small number of dose
changes required to maintain patients within the recommended tacrolimus target
levels. Tacrolimus is distributed extensively in the body with most partitioned
outside the blood compartment. Concentrations of tacrolimus in blood are used
as a surrogate marker of clinically relevant concentration of the drug at the
site(s) of action. Convenient whole-blood sampling within a +/-2-h window
around 12 h post-dose (C(min)) is highly predictive of systemic exposure to
tacrolimus and is thus used to optimise therapy. Sampling at other time-points
offers no advantage over C(min) monitoring. The interactions of tacrolimus with
other immunosuppressive agents are well characterized. After cessation of
concomitant corticosteroid treatment, exposure to tacrolimus increases by
approximately 25%. In contrast, there is no pharmacokinetic interaction between
mycophenolate mofetil (MMF) and tacrolimus. Therefore, systemic exposure to the
active metabolite of MMF, mycophenolic acid, is higher with MMF-tacrolimus
combination than with MMF-cyclosporin combination. Therefore, 1 g/day MMF may
be an adequate maintenance dose in tacrolimus-based regimens. Co-administration
of tacrolimus and sirolimus, while having no effect on exposure to sirolimus,
results in reduced exposure to tacrolimus at sirolimus doses of 2 mg/day and
above. In conclusion, tacrolimus levels should be monitored when sirolimus is
co-administered at doses >2 mg/day and after cessation of corticosteroid
treatment. N. Ref:: 13
----------------------------------------------------
[128]
TÍTULO / TITLE: - A pharmacokinetic and
clinical review of the potential clinical impact of using different
formulations of cyclosporin A. Berlin, Germany, November 19, 2001.
REVISTA
/ JOURNAL: - Clin Ther 2003 Jun;25(6):1654-69.
AUTORES
/ AUTHORS: - Pollard S; Nashan B; Johnston A; Hoyer P;
Belitsky P; Keown P; Helderman H
INSTITUCIÓN
/ INSTITUTION: - Department of Organ Transplantation, St.
James’s University Hospital, Leeds, United Kingdom.
RESUMEN
/ SUMMARY: - A meeting of 14 transplant and
pharmacokinetic specialists from Europe and North America was convened in
November 2001 to evaluate scientific and clinical data regarding the use of
different formulations of cyclosporin A (CsA). The following consensus was
achieved. (1) CsA is a critical-dose drug with a narrow therapeutic window.
Clinical outcomes after transplantation are affected by the pharmacokinetic
properties of CsA, particularly by its bioavailability, and by intrapatient
variability in CsA exposure. (2) Standard bioequivalence criteria do not
address differences in CsA pharmacokinetics between transplant recipients and healthy
volunteers, or between subpopulations of transplant recipients. (3) In some
circumstances, currently available formulations of CsA that meet standard
bioequivalence criteria are likely to be nonequivalent with respect to
pharmacokinetic characteristics. (4) The choice of CsA formulation can affect
the short- and long-term clinical outcome. Currently, there is a lack of
clinical comparisons between generic CsA formulations and the Neoral
formulation (Novartis Pharmaceuticals Corporation, East Hanover, New Jersey).
Initial retrospective data from the Collaborative Transplant Study suggest that
use of generic CsA formulations may result in reduced graft survival at 1 year.
(5) Management of transplant recipients by monitoring Neoral concentrations 2
hours after dosing (C(2)) reduces the incidence and severity of acute rejection
compared with monitoring of trough concentrations with no increase in toxicity.
C(2) monitoring has been developed based on the pharmacokinetics of Neoral only
and has not been evaluated or validated for generic formulations of CsA. (6)
The major costs of care after transplantation relate to the management of poor
clinical outcomes and toxicity. CsA formulations with different pharmacokinetic
properties may be associated with varying clinical outcomes, which would be
expected to affect total health care costs. (7) The transplant physician is
responsible for selecting immunosuppressive agents and formulations for his or
her patients. Any switch between CsA formulations in a particular patient
should take place only in a controlled setting with adequate pharmacokinetic
monitoring. N. Ref:: 51
----------------------------------------------------
[129]
- 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
----------------------------------------------------
[130]
TÍTULO / TITLE: - Current
immunosuppressive agents: efficacy, side effects, and utilization.
REVISTA
/ JOURNAL: - Pediatr Clin North Am 2003
Dec;50(6):1283-300.
AUTORES
/ AUTHORS: - Smith JM; Nemeth TL; McDonald RA
INSTITUCIÓN
/ INSTITUTION: - Division of Nephrology, Children’s
Hospital and Regional Medical Center, 4800 Sand Point Way, NE 5G-1, Seattle, WA
98105-0371, USA. jodi.smith@seattlechildrens.org
RESUMEN
/ SUMMARY: - Advances in immunosuppressive therapy over
the past decade have led to dramatic improvements in graft survival. With the
development of new agents, the focus of the transplant community is to
establish regimens that maintain excellent graft survival rates but with fewer
toxicities including infection, nephrotoxicity, malignancy, and cosmetic
effects. Examples include the use of steroid-free protocols and calcineurin
avoidance regimens, which are currently being studied by NAPRTCS. The ultimate
goal of transplant immunosuppressive therapy is the induction of tolerance. As
we learn more about immune function from basic and clinical research, tolerance
to allografts seems a more reachable goal.
N. Ref:: 89
----------------------------------------------------
[131]
TÍTULO / TITLE: - Transcending
conventional therapies: the role of biologic and other novel therapies.
REVISTA
/ JOURNAL: - Inflamm Bowel Dis 2001 May;7 Suppl
1:S9-16.
AUTORES
/ AUTHORS: - Sandborn WJ
INSTITUCIÓN
/ INSTITUTION: - Mayo Medical School, Rochester, Minnesota
55905, USA.
RESUMEN
/ SUMMARY: - Biologic and other novel therapies
targeted to specific pathogenic processes offer the potential for improved
treatment outcomes in patients with Crohn’s disease and alteration of the
course of the disease. Therapies targeted to tumor necrosis factor alpha
(TNF-alpha) include anti-TNF-alpha monoclonal antibodies (infliximab and
CDP-571), TNF-binding neutralizing fusion proteins (etanercept), and TNF-alpha
production inhibitors (thalidomide). In placebo-controlled trials, infliximab
has rapidly induced clinical response and remission in patients with moderately
to severely active Crohn’s disease refractory to conventional therapy and
patients with fistulizing Crohn’s disease, with minimal toxicity; retreatment
with infliximab in patients who experienced an initial response maintained
their clinical improvement. Clinical experience suggests that infliximab may
also be effective when administered as corticosteroid-sparing therapy.
Infliximab is the only anti-TNF-alpha therapy currently available in clinical
practice for the treatment of active Crohn’s disease. Controlled trials of the
investigational anti-TNF-alpha agent CDP-571 show benefit for induction of
clinical improvement and steroid-sparing, but further investigation is needed.
A pilot study of etanercept suggested a beneficial effect, but its efficacy was
not confirmed in a controlled trial. In open-label trials, thalidomide has
demonstrated efficacy in patients with refractory Crohn’s disease; however, the
therapeutic potential of thalidomide may be severely limited by the high
incidence of drug-induced side effects. Other novel agents, including
anti-alpha4 integrin antibodies, interleukin (IL)-10 and IL-11, and the
immunomodulators tacrolimus and mycophenolate mofetil have been evaluated as
treatment in patients with severely active or fistulizing Crohn’s disease in
open-label and controlled trials, with varied results reported to date. The
development of these new therapies is an exciting advance that promises to
improve the management of Crohn’s disease and expand current knowledge of
underlying pathophysiologic mechanisms.
N. Ref:: 32
----------------------------------------------------
[132]
TÍTULO / TITLE: - Mycophenolate mofetil
and leflunomide: promising compounds for the treatment of skin diseases.
REVISTA
/ JOURNAL: - Clin Exp Dermatol 2002 Oct;27(7):562-70.
AUTORES
/ AUTHORS: - Frieling U; Luger TA
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology, University of
Munster, Germany.
RESUMEN
/ SUMMARY: - In the past decade, there has been
enormous progress in the understanding of the pathomechanisms of
immune-mediated diseases, which has led to major advances in immunotherapeutic
strategies. As a consequence, the armamentarium of specific and nonspecific
immune-modulating and immunosuppressive drugs for the treatment of skin
diseases has been widely extended. Among the nonspecific immunomodulators,
mycophenolate mofetil and leflunomide show promising effects in a variety of
autoimmune and inflammatory skin disorders. Both compounds inhibit a key enzyme
in nucleotide biosynthesis, a step that is pivotal for the production of
cytotoxic T cells and antibody formation. They do not act in the nucleus, which
may explain their advantageous side-effect profile. N. Ref:: 68
----------------------------------------------------
[133]
TÍTULO / TITLE: - European best practice
guidelines for renal transplantation. Section IV: Long-term management of the
transplant recipient. IV.2.1 Differential diagnosis of chronic graft
dysfunction.
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 4:4-8.
RESUMEN
/ SUMMARY: - GUIDELINES: A. Any significant
deterioration in graft function should be investigated using the appropriate
diagnostic tools and, if possible, therapeutic interventions should be
initiated. The usual causes of a decline in glomerular filtration rate after
the first year include transplant-specific causes such as chronic allograft
nephropathy, acute rejection episodes, chronic calcineurin inhibitor
nephrotoxicity, transplant renal artery stenosis and ureteric obstruction, as
well as immunodeficiency-related causes and non-transplant-related causes, such
as recurrent or de novo renal diseases and bacterial infections. B. Any new
onset and persistent proteinuria of >0.5 g/24 h should be investigated and
therapeutic interventions should be initiated. The usual causes include chronic
allograft nephropathy and transplant glomerulopathy, and recurrent or de novo
glomerulonephritis.
----------------------------------------------------
[134]
TÍTULO / TITLE: - Approach to
corticosteroid-dependent and corticosteroid-refractory Crohn’s disease.
REVISTA
/ JOURNAL: - Inflamm Bowel Dis 2001 May;7 Suppl
1:S23-9.
AUTORES
/ AUTHORS: - Lichtenstein GR
INSTITUCIÓN
/ INSTITUTION: - Department of Medicine/Gastroenterology,
Hospital of the University of Pennsylvania, University of Pennsylvania School
of Medicine, Philadelphia 19104-4283, USA.
RESUMEN
/ SUMMARY: - Corticosteroids are considered a drug of
choice for the treatment of patients with moderately to severely active Crohn’s
disease (CD), an inflammatory bowel disease characterized by chronic recurrent
flares of disease activity. However, among patients receiving corticosteroid
therapy for induction of remission, 20% have corticosteroid-refractory disease
and 36% of those with an initial response develop corticosteroid dependency
within 1 year. Chronic corticosteroid exposure in patients who are
corticosteroid dependent increases the risk for serious drug-related adverse
effects. Withdrawal or reduction of corticosteroid therapy without exacerbation
of symptoms is therefore recognized as an important goal of treatment.
Therapies that have been shown to facilitate “steroid sparing’ include the
immunomodulators azathioprine/6-mercaptopurine and methotrexate and the
antitumor necrosis factor-alpha monoclonal antibody infliximab. In
corticosteroid-dependent patients, budesonide may be substituted for
conventional corticosteroid therapy without loss of response and with less risk
for toxicity, but its long-term efficacy requires further evaluation. A
preliminary controlled study suggests that the investigational anti-TNF
monoclonal antibody CDP-571 may also be clinically beneficial as a
corticosteroid-sparing agent. This review summarizes the clinical evidence that
supports consideration of these agents as alternatives in patients with CD who
are dependent on, refractory to, or intolerant of conventional corticosteroid
therapy. N. Ref:: 43
----------------------------------------------------
[135]
TÍTULO / TITLE: - Primary intestinal
posttransplant T-cell lymphoma.
REVISTA
/ JOURNAL: - Transplantation 2003 Jun 27;75(12):2131-2.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000060253.54333.F3
AUTORES
/ AUTHORS: - Michael J; Greenstein S; Schechner R;
Tellis V; Vasovic LV; Ratech H; Glicklich D
INSTITUCIÓN
/ INSTITUTION: - Division of Nephrology, Albert Einstein
College of Medicine, Montefiore Medical Center, Bronx, New York 10467, USA.
RESUMEN
/ SUMMARY: - There have been only five reported cases
of primary posttransplant T-cell lymphoma. We report the first case associated
with the use of sirolimus (Rapamycin, Wyeth-Ayerst, Philadelphia, PA). The
patient, receiving prednisone, cyclosporine, and sirolimus treatment, developed
ascites, diarrhea, and weight loss 7 months after his second renal transplant.
Tissue obtained at laparotomy established the diagnosis of primary T-cell
lymphoma. Latent membrane protein-1 for Epstein-Barr virus was negative, but
in-site hybridization test for Epstein-Barr-encoded RNA was positive. Despite
aggressive chemotherapy, the patient died 8 months posttransplant. This is the
sixth reported case of primary intestinal posttransplant T-cell lymphoma, but
it is the first case associated with the use of sirolimus. The incidence of
posttransplant lymphoproliferative disease in patients receiving sirolimus
should be studied. N.
Ref:: 6
----------------------------------------------------
[136]
- Castellano -
TÍTULO / TITLE:Alteraciones del metabolismo oseo
tras el trasplante renal. Bone metabolism alterations after kidney transplantation.
REVISTA
/ JOURNAL: - Nefrologia. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.aulamedica.es/nefrologia/
●●
Cita: Nefrologia: <> 2003;23 Suppl 2:122-6.
AUTORES
/ AUTHORS: - Torres A; Garcia S; Barrios Y; Hernandez
D; Lorenzo V
INSTITUCIÓN
/ INSTITUTION: - Servicio de Nefrologia, Unidad de
Investigacion, Hospital Universitario de Canarias, Instituto Reina Sofia de
Investigacion. atorres@ull.es
RESUMEN
/ SUMMARY: - Early after renal transplantation (RT) a
rapid decrease in bone mineral density at the lumbar spine, femoral neck, and
femoral shaft has been documented. In addition, an appreciable proportion of
patients still remain losing bone late after RT. As a consequence, RT patients
are at a high risk of bone fractures as compared to general population. Most
fractures involve appendicular skeleton, particularly the feet and ankles, and
the diabetic patient is at increased risk of fractures. Thus, early institution
of preventive measures and treatment of established osteoporosis are central.
The major cause of post-transplantation bone loss is corticosteroid treatment,
and this should be used at the lower dose compatible with graft survival.
Preexisting hyperparathyroidism also affects the early cancellous bone loss at
the spine, and post-transplantation bone loss reflects variable individual
susceptibility, resembling the polygenic determination of bone mineral density
in general. Clinical trials have demonstrated that bisphosphonates or vitamin D
plus calcium supplementation, prevent post-transplantation bone loss during the
first 6-12 months. However, their role in preventing bone fractures has not
been proven. Finally, recommendations for management, prevention and treatment,
are summarized. N.
Ref:: 24
----------------------------------------------------
[137]
- Castellano -
TÍTULO / TITLE:Tratamiento de la enfermedad de
Behcet. Behcet’s disease therapy review.
REVISTA
/ JOURNAL: - An Med Interna 2002 Nov;19(11):594-8.
AUTORES
/ AUTHORS: - Vidaller Palacin A; Robert Olalla J; Sanuy
Jimenez B; Rufi Rigau G; Folch Civit J; Charte Gonzalez A
INSTITUCIÓN
/ INSTITUTION: - Departamento de Medicina Interna, Unidad
de Diagnostico y Seguimiento de Inmunologia Clinica y Alergias, Institut
Universitari Dexeus, C/Calatrava, 83, 08017 Barcelona.
RESUMEN
/ SUMMARY: - Behcet’s disease is an inflammatory
process of unknown origin, which usually presents with recurrent oral ulcers,
genital aphthae, uveitis and cutaneous lesions. However, a wide variety of
clinical manifestations have been reported, and virtually any organ system may
be affected, showing central nervous system, joints, blood vessels or
gastrointestinal tract involvement. Therapeutic approach remains complex, and
varies in basis of the affected organs. Complex aphthosis may respond to
topical therapy, colchicine and dapsone. If this therapy does not result in
adequate disease control, thalidomide, oral prednisone and methotrexate may be
useful. When severe ocular lesions or systemic manifestations are present,
therapies tend to be more aggressive, usually combining corticosteroids with
immunosuppressive agents as cyclosporin, azathioprine, cyclophosphamide,
interferon-alfa-2a, and chlorambucil. N.
Ref:: 24
----------------------------------------------------
[138]
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.
----------------------------------------------------
[139]
TÍTULO / TITLE: - Efficacy and toxicity
of a protocol using sirolimus, tacrolimus and daclizumab in a nonhuman primate
renal allotransplant model.
REVISTA
/ JOURNAL: - Am J Transplant 2002 Apr;2(4):381-5.
AUTORES
/ AUTHORS: - Montgomery SP; Mog SR; Xu H; Tadaki DK;
Hirshberg B; Berning JD; Leconte J; Harlan DM; Hale D; Kirk AD
INSTITUCIÓN
/ INSTITUTION: - NIDDK/Navy Transplantation and
Autoimmunity Branch, Naval Medical Research Center, Bethesda, Maryland 20892,
USA.
RESUMEN
/ SUMMARY: - A regimen combining sirolimus, tacrolimus,
and daclizumab has recently been shown to provide adequate immunosuppression
for allogeneic islet transplantation in humans, but remains unproven for
primarily vascularized allografts. We evaluated this regimen for renal
allograft transplantation in mismatched nonhuman primates. Dosages of sirolimus
and tacrolimus were adjusted for trough levels of 10-15 ng/mL and 4-6 ng/mL,
respectively. Treated monkeys (n = 5) had significantly prolonged allograft
survival, with a mean survival of 36 days vs. 7 days in untreated controls (n =
6, p = 0.008). Four of five treated animals, but none of the controls,
developed fibrinoid vascular necrosis of the small intestine. A review of gut
histology from animals on other immunosuppressive protocols performed by our
laboratory suggested that these lesions were a result of sirolimus exposure. In
summary, this regimen prolongs the survival of vascularized renal allografts,
but is limited by profound GI toxicity in rhesus macaques.
----------------------------------------------------
[140]
TÍTULO / TITLE: - Atopic dermatitis and
asthma: parallels in the evolution of treatment.
REVISTA
/ JOURNAL: - Pediatrics 2003 Mar;111(3):608-16.
AUTORES
/ AUTHORS: - Eichenfield LF; Hanifin JM; Beck LA; Lemanske
RF Jr; Sampson HA; Weiss ST; Leung DY
INSTITUCIÓN
/ INSTITUTION: - Pediatric and Adolescent Dermatology,
Children’s Hospital, San Diego, CA 92123, USA. leichenfield@ucsd.edu
RESUMEN
/ SUMMARY: - OBJECTIVES: To review epidemiologic
correlations between asthma and atopic dermatitis (AD), identify common
features in disease pathophysiology, and review steps involved in the
development of asthma therapy guidelines to assess the appropriateness of a
similar process and approach for AD. METHODS: A 7-member panel representing
specialists in dermatology, allergy, asthma, immunology, and pediatrics from
around the United States convened to review the current literature and evolving
data on AD. Participants presented reviews to the panel on the epidemiology of
asthma and AD, the genetic predisposition to allergic disease, the current
understanding of the immunopathophysiology of AD, interrelationships between
the pathologic pathways of asthma and AD, evolving treatment concepts and
options in AD, and the applicability of the asthma treatment model and how it
may be adapted for guideline development for AD. Commentary and criticism were
recorded for use in document preparation. RESULTS: There are clear epidemiologic
parallels in asthma and AD. Importantly, AD frequently is the first
manifestation of an atopic diathesis, which occurs in genetically predisposed
individuals and also includes asthma and allergic rhinitis. Up to 80% of
children with AD will eventually develop allergic rhinitis or asthma later in
childhood. This classic “atopic triad” has numerous pathophysiologic elements
in common, including cyclic nucleotide regulatory abnormalities, immune cell
alterations, and inflammatory mediators and allergic triggers. New therapeutic
options that target underlying immune mechanisms are available, and their place
among treatments for AD is becoming established. Guidelines of care have been
developed for asthma. The panel noted that the National Institutes of Health/National
Heart, Lung, and Blood Institute guidelines for diagnosis and management of
asthma, first issued in 1991, had a tremendous positive impact on many aspects
of asthma treatment. It not only created a heightened awareness that asthma is
a disease of chronic inflammation, but it also provided unified approaches for
therapy and opened new areas of basic science and clinical research. In
addition, the guidelines spurred interactions among physicians of various
specialties and stimulated a great quantity of research in asthma therapy. It
is anticipated that AD therapy guidelines would have similar positive outcomes.
CONCLUSIONS: The panel concluded that, on the basis of current information and
evolving therapeutic options, a clear rationale exists to support AD guideline
development. The many parallels between AD and asthma suggest that processes
and approaches used for the asthma therapy guidelines would be appropriate for
AD. N. Ref:: 60
----------------------------------------------------
[141]
TÍTULO / TITLE: - Treatment responses of
childhood aplastic anaemia with chromosomal aberrations at diagnosis.
REVISTA
/ JOURNAL: - Br J Haematol 2002 Jul;118(1):313-9.
AUTORES
/ AUTHORS: - Ohga S; Ohara A; Hibi S; Kojima S; Bessho
F; Tsuchiya S; Ohshima Y; Yoshida N; Kashii Y; Nishimura S; Kawakami K;
Nishikawa K; Tsukimoto I
INSTITUCIÓN
/ INSTITUTION: - Aplastic Anaemia Committee of the Japanese
Society of Paediatric Haematology, Tokyo, Japan. ohgas@pediatr.med.kyushu-u.ac.jp
RESUMEN
/ SUMMARY: - The clinical outcome of childhood aplastic
anaemia (AA) with aberrant cytogenetic clones at diagnosis was surveyed. Among
198 children with newly diagnosed AA registered with the AA Committee of the
Japanese Society of Paediatric Hematology between 1994 and 1998, cytogenetic
studies of bone marrow (BM) cells were completed in 159 patients. Apart from
one Robertsonian translocation, seven patients (4.4%) showed clonal chromosomal
abnormalities in hypoplastic BM without myelodysplastic features. The patients
included six girls and one boy with a median age of 11 years (range 5-14
years). Six patients had del(6), del(5), del(13), del(20), or -7, and one
showed add(9). Four patients responded to the first immunosuppressive therapy
(IST: cyclosporin A plus anti-thymocyte globulin) and one obtained a
spontaneous remission. Cytogenetic abnormalities remained in two patients with
an IST response. On the other hand, two patients showed no IST response. One
did not respond to repeat IST and died of acute graft-versus-host disease after
an unrelated-BM transplant. Another obtained a complete response after a
successful BM transplant. No haematological findings at diagnosis predicted the
treatment response. No significant morphological changes developed during the
course of the illness. A literature review revealed that half of 24 AA patients
with chromosomal abnormalities responded to the first IST, and that +6 was the
sole predictable marker for IST unresponsiveness. These results suggest that
IST can be applied as the initial therapy for AA with cytogenetic abnormalities
in the absence of completely matched donors.
N. Ref:: 32
----------------------------------------------------
[142]
TÍTULO / TITLE: - Immunosuppressive treatment
in dialysis patients.
REVISTA
/ JOURNAL: - Nephrol Dial Transplant. Acceso gratuito
al texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://ndt.oupjournals.org/
●●
Cita: Nephrology Dialysis Transplantation: <> 2002;17 Suppl 8:2-9.
AUTORES
/ AUTHORS: - Altieri P; Sau G; Cao R; Barracca A;
Menneas A; Micchittu B; Cabiddu G; Esposito P; Pani A
INSTITUCIÓN
/ INSTITUTION: - Renal Department, Ospedale San Michele,
Cagliari, Italy.
RESUMEN
/ SUMMARY: - Immunosuppressive treatment is a critical
procedure in dialysis patients, in whom an increased risk of infection is
already present. Haemodialytic treatment increases the patient’s susceptibility
to bacterial infection, mainly by impairing polymorphonuclear leukocyte
phagocytosis, but it can also restore the patient’s immunological defences by
improving the T-cell function, which is reduced by pre-dialysis uraemia.
Patients on dialysis usually continue the immunosuppressive treatment that had
been established for the illness that caused their renal failure [e.g. systemic
lupus erythematosus (SLE) or renal vasculitis]. Less frequently, patients on
dialysis need immunosuppression for immunological or inflammatory diseases that
appear ‘de novo’ after initiation of dialysis. SLE and antineutrophil
cytoplasmic antibody (ANCA)-related vasculitides are immunological illnesses
that frequently cause end-stage renal failure (ESRF). A reduction in
serological and/or clinical activity is usually observed in SLE patients after
they reach ESRF, but a similar or increased frequency of extrarenal relapse
episodes in lupus patients after the beginning of the dialysis, compared with
the pre-dialysis period, has also been described. Frequency of relapse episodes
in patients on dialysis treatment for ANCA-related vasculitides varies from 10
to 30% per patient/year in different reports, and it is higher than the
frequency of relapses after renal transplantation; anti-rejection therapy seems
to be the most likely protective factor in these conditions. The treatment of
relapse episodes in SLE or ANCA vasculitis in dialysis-dependent patients is
usually not different from treatment of relapses in patients with
dialysis-independent renal function. However, the risk of severe infection
caused by immunosuppressive treatment is relevantly higher in dialysis
patients. Furthermore, there is a lack of prospective controlled studies
indicating the optimal management of immunosuppressive protocols in dialysis
patients. A particularly careful assessment of the patient’s risks and benefits
is necessary in deciding how long immunosuppressive treatment should last after
acute or rapidly progressive renal damage, that should require dialysis treatment,
in patients with SLE or ANCA vasculitis. In the above conditions, the risks of
prolonging immunosuppressive treatment must be balanced against the relatively
good prognosis offered to these patients by dialysis and renal transplantation.
In a retrospective review of 24 patients receiving long-term steroid therapy
(>3 months) in our dialysis unit in the past 5 years, we found relevant
clinical differences in the patients receiving steroid treatment compared with
24 controls. Steroid-treated patients showed less favourable nutritional
conditions, with lower serum albumin and body mass index vs non-steroid-treated
patients; moreover, C-reactive protein values were persistently higher in the
steroid-treated group. Steroid treatment in these patients was usually
performed at the beginning of regular dialysis, as a continuation of the
treatment that started before the initiation of dialysis. Only two patients,
who needed a prolonged low-dose steroidal treatment to control a
malnutrition-inflammation-atherosclerosis (MIA) syndrome, started steroids many
years after beginning dialysis. Steroid treatment was effective in improving
the nutritional condition and inflammatory symptoms in these two patients after
all conventional measures had failed. N.
Ref:: 45
----------------------------------------------------
[143]
TÍTULO / TITLE: - Acute necrotizing
gastritis by Escherichia coli in a severely neutropenic patient.
REVISTA
/ JOURNAL: - Haematologica. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://db.doyma.es/
●●
Cita: Haematologica: <> 2002 Jan;87(1):ELT01.
AUTORES
/ AUTHORS: - Martinez-Chamorro C; Martinez E;
Gil-Fernandez JJ; Escudero A; Acevedo A; Fernandez-Ranada JM
INSTITUCIÓN
/ INSTITUTION: - Hematology Department, Clinica Ruber,
C/Juan Bravo, 49 28006-Madrid, España. m-chamorro@navegalia.com N. Ref:: 6
----------------------------------------------------
[144]
- Castellano -
TÍTULO / TITLE:Bioequivalencia e intercambio
terapeutico de especialidades farmaceuticas: aplicacion a ciclosporina en
trasplante renal. Bioequivalence and therapeutic exchange of pharmaceutical
specialties: application to cyclosporin in renal transplantation.
REVISTA
/ JOURNAL: - Nefrologia. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.aulamedica.es/nefrologia/
●●
Cita: Nefrologia: <> 2003;23(1):71-80.
AUTORES
/ AUTHORS: - Perez Ruixo JJ; Porta B; Jimenez Torres NV
INSTITUCIÓN
/ INSTITUTION: - Global Clinical Pharmacokinetics and
Clinical Pharmacology Division, Johnson & Johnson Pharmaceutical Research
and Development, Turnhoutseweg, 30, B-2230 Beerse, Belgica. jperezru@janbe.jnj.com
RESUMEN
/ SUMMARY: - The aim of this study was to perform a
quantitative meta-analysis of the average bioequivalence criteria between
Sandimmun and Sandimmun Neoral in kidney transplant patients, and to review the
new bioequivalence criteria and their application to generic formulation of
cyclosporin. In Medline, we searched for clinical trials evaluating the
bioequivalence between Sandimmun and Sandimmun Neoral in kidney transplant
patients and we collected the information regarding the bioequivalence, study
design, sample size, and time post-transplant. The effect was measured by the
Wolf method; publication bias was evaluated by the Galbraith method and the
Rosenthal formula was used to calculate the number of additional studies with
no statistical differences needed to get a statistically non-significant
overall estimation. We selected 6 clinical trials with a latin square design
and 4 clinical trials with sequential design. The average bioequivalence
criteria between Sandimmun Neoral and Sandimmun were 1.327 (90% CI: 1,311 a
1,344), 1,663 (90% CI: 1,635 a 1,692) and 0.559 hours (90% CI: 0.544 a 0.574
hours) for logharitmic transformation of area under the curve and maximum
concentration, and time to maximum concentration, respectively. For these three
outcomes, we found statistical differences between different study designs and
for area under the curve and maximum concentration, the average bioequivalence
criteria significantly fall with the post-transplant time. We conclude
Sandimmun Neoral and Sandimmun are not bioequivalents and the experience
reached with these two drugs is not applicable to the evaluation of generic
formulations of cyclosporin.
----------------------------------------------------
[145]
TÍTULO / TITLE: - Treatment of membranous
nephropathy.
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: <> 2001;16 Suppl 5:8-10.
AUTORES
/ AUTHORS: - Ponticelli C; Passerini P
INSTITUCIÓN
/ INSTITUTION: - Division of Nephrology, Ospedale Maggiore
di Milano, Italy.
RESUMEN
/ SUMMARY: - Several therapeutic approaches have been
tried in patients with membranous nephropathy. Corticosteroids have been
largely used, but a meta-analysis of the available controlled trials did not
show any benefit of corticosteroids either in favouring remission of the
nephrotic syndrome or in preventing renal dysfunction. Controversial results
have been obtained with cytotoxic agents. Unfortunately, most of the available
trials were small in size and had short-term follow-ups. Three controlled
trials evaluated the role of a 6-month treatment with methylprednisolone and
chlorambucil. The first trial showed that the 10-year renal survival rate was
92% in treated patients compared with 60% in untreated controls. A second trial
compared the effects of methylprednisolone/chlorambucil with those of
methylprednisolone alone. The combined treatment achieved remission of
nephrotic syndrome in 64% of cases vs 38% in patients given steroids alone. A
third trial showed equivalent results in patients randomized to be given
methylprednisolone/chlorambucil or methylprednisolone/cyclophosphamide. A
number of non-controlled studies and a randomized trial also showed the
efficacy of cyclosporine in reducing proteinuria. In many but not all cases,
proteinuria reappeared when cyclosporine was stopped. In conclusion, although
the treatment of membranous nephropathy remains difficult, some therapeutical
approaches have proved to favour remission and protect renal function N. Ref:: 53
----------------------------------------------------
[146]
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
----------------------------------------------------
[147]
TÍTULO / TITLE: - Vitamin D and systemic
therapy.
REVISTA
/ JOURNAL: - Cutis 2002 Nov;70(5 Suppl):16-20.
AUTORES
/ AUTHORS: - van de Kerkhof P
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology, University
Hospital, Nijmegen, Netherlands.
RESUMEN
/ SUMMARY: - The most frequently used systemic
treatments for severe psoriasis are methotrexate (MTX), oral retinoids, and
cyclosporine; however, all of these agents are associated with dose-related
toxicities that limit their use. The safety and efficacy of topical
calcipotriene for the treatment of psoriasis have been demonstrated in numerous
clinical studies. The rationale for using calcipotriene in combination with
systemic therapies is based on their different modes of action and nonoverlapping
side effects. Three controlled clinical trials have demonstrated that the
addition of calcipotriene ointment to systemic antipsoriatic treatment with
MTX, acitretin, and cyclosporine increases the therapeutic efficacy compared
with systemic therapy alone and minimizes side effects by either reducing the
dosage or duration of treatment. N.
Ref:: 18
----------------------------------------------------
[148]
TÍTULO / TITLE: - Lichen amyloidosus
associated with Kimura’s disease: successful treatment with cyclosporine.
REVISTA
/ JOURNAL: - Dermatology 2002;204(2):133-5.
AUTORES
/ AUTHORS: - Teraki Y; Katsuta M; Shiohara T
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology, Kyorin
University School of Medicine, Tokyo, Japan. teraki@kyorin-u.ac.jp
RESUMEN
/ SUMMARY: - We describe here a case of a 33-year-old
man who had lichen amyloidosus associated with Kimura’s disease. In this case,
treatment with cyclosporine dramatically improved the lesions of both Kimura’s
disease and lichen amyloidosus. Although Kimura’s disease and lichen
amyloidosus are both rare distinct entities, to our knowledge, 11 cases of
association of Kimura’s disease and lichen amyloidosus have been described
previously. N. Ref:: 13
----------------------------------------------------
[149]
TÍTULO / TITLE: - Pimecrolimus: a review.
REVISTA
/ JOURNAL: - J Eur Acad Dermatol Venereol 2003
Sep;17(5):493-503.
AUTORES
/ AUTHORS: - Gupta AK; Chow M
INSTITUCIÓN
/ INSTITUTION: - Division of Dermatology, Department of
Medicine, Sunnybrook and Women’s College Health Science Center (Sunnybrook
site) and the University of Toronto, Toronto, Canada. agupta@execulink.com
RESUMEN
/ SUMMARY: - Pimecrolimus (SDZ ASM 981), an ascomycin
derivative, is one of the new classes of immunomodulating macrolactams and was
specifically developed for the treatment of inflammatory skin diseases. The
interest in pimecrolimus has been substantial because of its significant
anti-inflammatory activity and immunomodulatory capabilities and its low
systemic immunosuppressive potential. The mechanism of action of pimecrolimus
is the blockage of T cell activation. Pimecrolimus (like all ascomycins) is an
immunophilin ligand, which binds specifically to the cytosolic receptor,
immunophilin macrophilin-12. This pimecrolimus-macrophilin complex effectively
inhibits the protein phosphatase calcineurin, by preventing calcineurin from
dephosphorylating the nuclear factor of activated T cells (NF-AT), a
transcription factor. This results in the blockage of signal transduction
pathways in T cells and the inhibition of the synthesis of inflammatory
cytokines, specifically Th1- and Th2-type cytokines. Pimecrolimus has also been
shown to prevent the release of cytokines and pro-inflammatory mediators from
mast cells. Several studies have evaluated the effectiveness of pimecrolimus as
a treatment for skin diseases. In animal models of allergic contact dermatitis,
topical pimecrolimus was found to be effective. In human studies of allergic
contact dermatitis pimecrolimus demonstrated significantly more efficacy than
the control treatment. As well, the effectiveness of pimecrolimus 0.6% cream
was comparable to 0.1% betamethasone-17-valerate; however, pimecrolimus was not
associated with any of the side effects characteristic of a topical steroid.
Topical application of pimecrolimus is not associated with skin atrophy.
Pimecrolimus is effective and safe in both children and adults with atopic
dermatitis. When pimecrolimus 1% cream has been applied to adult atopics,
improvement has been observed as early as the first week, with a 72% reduction
in severity after 3 weeks. Pharmacokinetic studies have shown very low blood
levels of pimecrolimus following topical application, with no accumulation
after repeated applications. Following application of pimecrolimus cream
occasional transient irritation may be experienced at the application site.
Similar results have also been found in children aged 3 months and older
following application of pimecrolimus 1% cream. Topical pimecrolimus in
psoriasis appears to exhibit a dose-dependent therapeutic effect under
semi-occlusive conditions. Pimecrolimus has an enormous potential as a new
treatment of inflammatory skin diseases. It has been shown to be effective in
atopic and allergic contact dermatitis, with a favorable adverse-effects
profile, which includes little effect on the systemic immune response. N. Ref:: 42
----------------------------------------------------
[150]
TÍTULO / TITLE: - Rapamycin in
transplantation: a review of the evidence.
REVISTA
/ JOURNAL: - Kidney Int 2001 Jan;59(1):3-16.
AUTORES
/ AUTHORS: - Saunders RN; Metcalfe MS; Nicholson ML
INSTITUCIÓN
/ INSTITUTION: - Department of Surgery, Leicester General
Hospital, Leicester, England, United Kingdom. rnsaunders@hotmail.com
RESUMEN
/ SUMMARY: - Rapamycin in transplantation: A review of
the evidence. The calcineurin inhibitors have been the mainstays of
immunosuppression for solid organ transplantation over the last two decades,
but nephrotoxicity limits their therapeutic benefit. Rapamycin is a new drug
with both immunosuppressant and antiproliferative properties that has a unique
mechanism of action distinct from that of the calcineurin inhibitors. It has a
role as a maintenance immunosuppressant either alone or in combination with a
calcineurin inhibitor and can also be used to treat refractory acute rejection.
Theoretical evidence suggests that it may limit the development and progression
of chronic rejection in transplant recipients, but this has yet to be
confirmed. This review examines the current in vitro animal and human work
underlying the use of rapamycin and, in addition, comments on the
pharmacokinetics and side-effect profile of this promising new agent. N. Ref:: 122
----------------------------------------------------
[151]
TÍTULO / TITLE: - Inhibitors of mammalian
target of rapamycin as novel antitumor agents: from bench to clinic.
REVISTA
/ JOURNAL: - Curr Opin Investig Drugs 2002
Feb;3(2):295-304.
AUTORES
/ AUTHORS: - Huang S; Houghton PJ
INSTITUCIÓN
/ INSTITUTION: - Department of Molecular Pharmacology, St
Jude Children’s Research Hospital, Memphis, TN 38105-2794, USA.
RESUMEN
/ SUMMARY: - Rapamycin and its derivatives, CCI-779 and
RAD-001, inhibit the mammalian target of rapamycin (mTOR), downregulating
translation of specific mRNAs required for cell cycle progression from G1 to S
phase. Preclinically, mTOR inhibitors potently suppress growth and
proliferation of numerous tumor cell lines in culture or when grown in mice as
xenografts. CCI-779 and RAD-001 are being developed as antitumor drugs and are
undergoing clinical trials. Clinically, CCI-779 has shown evidence of antitumor
activity but induced relatively mild side effects in patients. Here we discuss
potential antitumor mechanisms and resistance mechanisms of mTOR inhibitors,
and summarize the current status of these compounds as novel antitumor agents. N. Ref:: 90
----------------------------------------------------
[152]
TÍTULO / TITLE: - Regulation of
translation via TOR signaling: insights from Drosophila melanogaster.
REVISTA
/ JOURNAL: - J Nutr. Acceso gratuito al texto completo
a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.nutrition.org/
●●
Cita: Journal of Nutrition: <> 2001 Nov;131(11):2988S-93S.
AUTORES
/ AUTHORS: - Miron M; Sonenberg N
INSTITUCIÓN
/ INSTITUTION: - Department of Biochemistry and McGill
Cancer Center, McGill University, Montreal, Quebec, Canada.
RESUMEN
/ SUMMARY: - The target of rapamycin (TOR) proteins are
large protein kinases evolutionarily conserved from yeast to human. A large
body of evidence demonstrates that TOR proteins function in a nutrient-sensing
checkpoint whose role is to restrict growth under conditions of low nutrient
availability. Under such conditions, TOR blocks the transmission of
growth-promoting signals from extracellular stimuli. Recent data obtained by
genetic studies in the fruit fly Drosophila melanogaster demonstrate the
importance of both insulin-like signaling and TOR signaling in promoting
growth. Importantly, these studies identified a major downstream target of TOR
and insulin-like signaling as the translational machinery. N. Ref:: 63
----------------------------------------------------
[153]
TÍTULO / TITLE: - International
Federation of Clinical Chemistry/International Association of Therapeutic Drug
Monitoring and Clinical Toxicology working group on immunosuppressive drug
monitoring.
REVISTA
/ JOURNAL: - Ther Drug Monit 2002 Feb;24(1):59-67.
AUTORES
/ AUTHORS: - Holt DW; Armstrong VW; Griesmacher A;
Morris RG; Napoli KL; Shaw LM
INSTITUCIÓN
/ INSTITUTION: - Analytical Unit, St George’s Hospital
Medical School, London, UK. d.holt@sghms.ac.uk
RESUMEN
/ SUMMARY: - Issues surrounding the measurement and
interpretation of immunosuppressive drug concentrations have been summarized in
a number of consensus documents. The Scientific Division of the International
Federation of Clinical Chemistry has formed a working group in collaboration
with the International Association of Therapeutic Drug Monitoring and Clinical
Toxicology. This paper sets out the goals of the working group in light of the
developments that have occurred in the field of immunosuppressive drug
monitoring since the publication of the last consensus documents.
----------------------------------------------------
[154]
TÍTULO / TITLE: - European best practice
guidelines for renal transplantation. Section IV: Long-term management of the
transplant recipient. IV.2.5. Chronic graft dysfunction. Late recurrence of
primary glomerulonephritides.
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 4:16-8.
RESUMEN
/ SUMMARY: - GUIDELINES: A. In the case of recurrent
focal and segmental glomerulosclerosis (FSGS), aggressive treatment with
high-dose cyclosporine in children, ACE inhibitors and/or Angiotensin II
antagonists, plasma exchange or immunoadsorption may result in remission in
some patients. B. In the case of recurrent membranous nephropathy (MN), there
is no specific treatment. However, control of risk factors, such as
hypertension, heavy proteinuria and hyperlipidaemia, and prevention of
thrombotic complications are recommended. C. In the case of recurrent
membranoproliferative glomerulonephritis (MPGN), there is no specific
treatment. However, control of risk factors, such as hypertension, heavy
proteinuria and hyperlipidaemia, and prevention of thrombotic complications are
recommended. D. In the case of recurrent IgA glomerulonephritis, use of
additional steroids is not yet a validated treatment. The control of risk
factors, such as hypertension, heavy proteinuria and hyperlipidaemia, is
recommended. E. In the rare case of recurrent anti-glomerular basement membrane
(anti-GBM) glomerulonephritis with reappearance of anti-GBM antibodies, it is
recommended to initiate plasma exchange and to treat with appropriate
immunosuppressive agents (e.g. cyclophosphamide).
----------------------------------------------------
[155]
TÍTULO / TITLE: - Treatment of de novo
and recurrent membranous nephropathy in renal transplant patients.
REVISTA
/ JOURNAL: - Semin Nephrol 2003 Jul;23(4):392-9.
AUTORES
/ AUTHORS: - Poduval RD; Josephson MA; Javaid B
INSTITUCIÓN
/ INSTITUTION: - Department of Medicine, Section of
Nephrology, University of Chicago, Pritzker School of Medicine, IL 60637, USA.
RESUMEN
/ SUMMARY: - Membranous nephropathy (MN) is one of the
common glomerular diseases diagnosed in transplanted kidneys. The exact impact
of posttransplantation MN on the risk for graft loss and long-term graft
outcome is not defined clearly. In recent reports, it has emerged as the third
most frequent glomerulonephritis (de novo or recurrent) associated with renal
allograft loss. Most cases of posttransplantation MN are thought to be
idiopathic but cases associated with established secondary causes also have
been reported. Patients can present with varying degrees of proteinuria and
graft dysfunction. Risk factors that predict a poor outcome are not well
established and unlike MN in the native kidneys, spontaneous remission is rare.
Patients should be evaluated carefully for complications associated with
nephrotic syndrome or graft dysfunction and managed accordingly. The beneficial
effects of steroids, cyclosporine, mycophenolate mofetil, cyclophosphamide,
chlorambucil, or other agents have not been validated. The role of specific
treatments in cases of secondary MN is uncertain. Retransplantation is a
reasonable option for patients who develop graft failure secondary to MN. N. Ref:: 34
----------------------------------------------------
[156]
TÍTULO / TITLE: - Treatment of severe
acute graft-versus-host disease with anti-thymocyte globulin.
REVISTA
/ JOURNAL: - Clin Transplant 2001 Jun;15(3):147-53.
AUTORES
/ AUTHORS: - Remberger M; Aschan J; Barkholt L;
Tollemar J; Ringden O
INSTITUCIÓN
/ INSTITUTION: - Department of Clinical Immunology and
Centre for Allogeneic Stem Cell Transplantation, Karolinska Institutet,
Huddinge University Hospital, Stockholm, Sweden. mats.remberger@impi.ki.se
RESUMEN
/ SUMMARY: - Severe acute graft-versus-host disease
(GVHD) is one of the major complications after haematopoietic stem-cell
transplantation (HSCT). Treatment of severe GVHD is difficult and the condition
is often fatal. One proposed method of improving the therapy is to include
anti-thymocyte globulin (ATG). Here, we will report our results in 29 patients
using ATG as part of treatment for severe steroid-resistant acute GVHD. Four
patients suffered from grade II, 13 from grade III and 12 from grade IV GVHD.
Median time to grade II GVHD was 24 d (range 7-91 d) and to grade III was 29 d
(range 8-55 d) after HSCT. Five different ATG preparations were used, rabbit
ATG (R-ATG), BMA 031, OKT3, ATG-Fresenius and Thymoglobuline. All patients had
skin involvement, 26 also had gut involvement and 25 had liver involvement. The
rate of response to treatment was best in skin involvement (72%), while liver
and gut involvement showed lower response rates (38%). Eleven patients survived
more than 90 d, 7 of them developed chronic GVHD, 1 developed mild GVHD, 1
developed moderate GVHD and 5 developed severe GVHD. Survival at 100 d was 37%
and at 1 yr it was 12%. Most patients died of GVHD, with virus or fungal
infections as contributing causes of death. To conclude, treatment of severe
acute GVHD is difficult and ATG, in our hands, adds nothing to conventional
pharmacological treatment. N.
Ref:: 48
----------------------------------------------------
[157]
TÍTULO / TITLE: - The clinical and
immunologic impact of using interferon and ribavirin in the immunosuppressed
host.
REVISTA
/ JOURNAL: - Liver Transpl 2003 Nov;9(11):S79-89.
●●
Enlace al texto completo (gratuito o de pago) 1053/jlts.2003.50257
AUTORES
/ AUTHORS: - Braun M; Vierling JM
INSTITUCIÓN
/ INSTITUTION: - Center for Liver Diseases and
Transplantation and Burns and Allen Research Institute, Cedars-Sinai Medical
Center, and the David Geffen School of Medicine at UCLA, Los Angeles, CA 90048,
USA. vierling@csmc.edu
RESUMEN
/ SUMMARY: - 1. Allograft infection with hepatitis C
virus (HCV) in immunosuppressed adults results in decreased allograft and
patient survival. 2. Risk factors for accelerated progression of hepatitis C
related to immunosuppression include treated episodes of acute cellular
rejection (ACR), pulse therapy with methylprednisolone, and use of OKT3. 3.
Both interferon alfa (IFN-alpha) and ribavirin (RVN) show antiviral actions
against HCV and stimulate innate and adaptive immunity to increase cytolysis
and polarize T helper subtype 1 (T(H)1) responses. In addition, IFN-alpha
inhibits fibrogenesis in the liver. 4. Both IFN-alpha and RVN have been studied
in immunosuppressed liver transplant recipients as prophylaxis or treatment of
established hepatitis C to reduce allograft failure and patient mortality. Reported
protocols include monotherapies with RVN, standard IFN-alpha, and pegylated
IFN-alpha and combination therapies using RVN and either standard IFN-alpha or
pegylated IFN-alpha. 5. The clinical impact of using IFN-alpha and RVN in
highly selected immunosuppressed patients varied among studies. Combination
therapy with standard IFN-alpha and RVN resulted in the greatest sustained
biochemical and virological responses. However, no therapy prevented
progression of acute cholestatic hepatitis C despite evidence of virological
responses. Substantial proportions of patients developed adverse events
requiring dose reduction or discontinuation that compromised efficacy. RVN
monotherapy was not only virologically ineffective, but may have stimulated
hepatic fibrosis. Current data regarding monotherapy or combination therapy
with pegylated IFN-alpha are limited, but encouraging. 6. Despite potent
immunostimulatory actions of both IFN-alpha and RVN that enhance natural
killer, T(H)1, their use did not significantly increase the incidence of ACR.
7. Additional studies are needed to resolve the controversy over prophylaxis
versus treatment of established disease and the potential utility of low-dose
maintenance IFN-alpha therapy to retard fibrogenesis without clearing HCV. 8.
After new, less toxic, and more potent antiviral agents become available, they
should be tested immediately in patients with hepatitis C post-liver
transplantation. N.
Ref:: 81
----------------------------------------------------
[158]
TÍTULO / TITLE: - Reduced-intensity
conditioning followed by allogeneic hematopoietic cell transplantation in
myeloid diseases.
REVISTA
/ JOURNAL: - Ann Hematol 2003 Aug;82(8):463-8. Epub
2003 Jun 21.
●●
Enlace al texto completo (gratuito o de pago) 1007/s00277-003-0680-7
AUTORES
/ AUTHORS: - Platzbecker U; Ehninger G; Schmitz N;
Bornhauser M
INSTITUCIÓN
/ INSTITUTION: - Medical Clinic I, University Hospital Carl
Gustav Carus, Fetscherstrasse 74, 01307, Dresden, Germany.
RESUMEN
/ SUMMARY: - Within the past years, reduced or modified
doses of chemotherapy or radiotherapy have been widely studied for conditioning
before allogeneic hematopoietic cell transplantation in patients with myeloid
leukemia not eligible for conventional transplantation. The main goal was to
reduce the substantial treatment-related mortality in this patient population
while preserving the potential curative graft-versus-leukemia effect. This
review summarizes results of published trials using reduced-intensity
conditioning (RIC) in patients with acute myeloid leukemia (AML),
myelodysplastic syndrome (MDS), chronic myeloid leukemia (CML), and
myelofibrosis. In most of the published trials conditioning contained
fludarabine (90-180 mg/m(2)) in combination with busulfan (4 x 10 mg/kg),
melphalan (90-140 mg/m(2)), or 2-5 Gy total body irradiation (TBI). Peripheral
blood hematopoietic stem cells from related or unrelated donors were used as
graft source in most of the studies. Post-transplantation immunosuppression
consisted of cyclosporine combined with methotrexate or mycophenolate mofetil.
Although the majority of the patients were above the age of 50 years, early
treatment-related mortality was rather low. Nevertheless, the rate of clinically
significant graft-versus-host disease (GVHD) seemed to be comparable to
conventional transplants in most of the protocols. The outcome differed between
trials, but diagnosis and disease status pre-transplant significantly
influenced outcome. In summary, this approach is feasible and provides access
to the curative potential of allogeneic stem cell transplantation for patients
with higher age or comorbidities. Since the majority of the reports included
heterogeneous patient populations, mostly with a short follow-up, more and
specifically randomized studies are needed to define the role of RIC before
allogeneic hematopoietic cell transplantation.
N. Ref:: 32
----------------------------------------------------
[159]
TÍTULO / TITLE: - Mitochondrial
involvement in the point of no return in neuronal apoptosis.
REVISTA
/ JOURNAL: - Biochimie 2002 Feb-Mar;84(2-3):223-31.
AUTORES
/ AUTHORS: - Chang LK; Putcha GV; Deshmukh M; Johnson
EM Jr
INSTITUCIÓN
/ INSTITUTION: - Department of Neurology, Washington
University School of Medicine, 660 South Euclid Avenue, Campus Box 8103, St.
Louis, MO 63110-1031, USA.
RESUMEN
/ SUMMARY: - Programmed cell death (PCD) contributes to
development, maintenance, and pathology in various tissues, including the
nervous system. Many molecular, biochemical, and genetic events occur within
cells undergoing PCD. Some of these events are incompatible with long-term cell
survival because they have irreversible, catastrophic consequences. The onset
of such changes marks the point of no return, a decisive regulatory event
termed ‘the commitment-to-die.’ In this review, we discuss events that underlie
the commitment-to-die in nerve growth factor-deprivation-induced death of
sympathetic neurons. Findings in this model system implicate the mitochondrion
as an important site of regulation for the commitment-to-die in the presence or
absence of caspase inhibition. N.
Ref:: 57
----------------------------------------------------
[160]
TÍTULO / TITLE: - New aspects of the
treatment of nephrotic syndrome.
REVISTA
/ JOURNAL: - J Am Soc Nephrol. Acceso gratuito al texto
completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.jasn.org/
●●
Cita: Journal of the American Society of Nephrology: <> 2001 Feb;12 Suppl
17:S44-7.
AUTORES
/ AUTHORS: - Schwarz A
INSTITUCIÓN
/ INSTITUTION: - Department of Nephrology, Medizinische
Hochschule Hannover, Hanover, Germany. schwarz.anke@mh-hannover.de
RESUMEN
/ SUMMARY: - The nephrotic syndrome, caused by
glomerulonephritis, diabetes mellitus, or amyloidosis, is still a therapeutic
challenge. Newer therapeutic approaches may be sought in the fields of
immunosuppression, nonspecific supportive measures, heparinoid administration,
and removal of a supposed glomerular basement membrane toxic factor. In
immunosuppression, the newer drugs now used in organ transplantation
(cyclosporine, tacrolimus, and mycophenolate mofetil) can also be used in the
treatment of glomerulonephritis. In nonspecific supportive treatment,
angiotensin II receptor antagonists are now used in addition to
angiotensin-converting enzyme inhibitors. Positive effects of
hydroxymethylglutaryl coenzyme A reductase inhibitors on the nephrotic syndrome
have not yet been proven. Cyclooxygenase II inhibitors must be tested but
probably have too many renal side effects, similar to those of nonsteroidal
anti-inflammatory drugs. Heparinoids or glycosaminoglycans serve as polyanions
and thus have protective effects on the negative charge of the glomerular
basement membrane. They can now be administered as oral medications. The
removal of a supposed glomerular basement membrane toxic factor that induces
proteinuria has been attempted for 20 yr and now is usually performed using
immunoadsorption. Especially in cases of recurrent nephrotic syndrome after
renal transplantation for patients with glomerulonephritis, this approach has
been successful in decreasing proteinuria, although in most cases its effect is
not lasting but must be continuously renewed.
N. Ref:: 56
----------------------------------------------------
[161]
TÍTULO / TITLE: - Hyperlipidemia and
cardiovascular disease after organ transplantation.
REVISTA
/ JOURNAL: - Transplantation 2001 Sep 27;72(6
Suppl):S13-5.
AUTORES
/ AUTHORS: - Massy ZA
INSTITUCIÓN
/ INSTITUTION: - INSERM U507, Necker Hospital, Paris,
France. massy@necker.fr
RESUMEN
/ SUMMARY: - Hyperlipidemia, a frequent and persistent
complication after solid organ transplantation, contributes to cardiovascular
morbidity and mortality and may influence the development of allograft
vasculopathy. The pathogenesis of posttransplantation hyperlipidemia is not fully
understood, although several epidemiological factors are strongly implicated
including age, weight, pretransplantation lipid levels, and immunosuppressive
therapy. Management strategies to reduce hyperlipidemia and modify
cardiovascular risk include dietary restrictions and the use of lipid-lowering
agents. The selective use of immunosuppressants, such as tacrolimus, that have
neutral or fewer adverse effects on lipid metabolism may also provide a useful
option. A combination of lipid-lowering therapies and optimization of
immunosuppressive regimens compatible with prolonged allograft survival is
probably necessary to significantly reduce posttransplantation hyperlipidemia
and its potentially harmful consequences.
N. Ref:: 44
----------------------------------------------------
[162]
TÍTULO / TITLE: - Paraneoplastic
pemphigus in association with a retroperitoneal Castleman’s disease presenting
with a lichen planus pemphigoides-like eruption. A case report and review of
literature.
REVISTA
/ JOURNAL: - Br J Dermatol 2001 Feb;144(2):372-6.
AUTORES
/ AUTHORS: - Hsiao CJ; Hsu MM; Lee JY; Chen WC; Hsieh
WC
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology, National
Cheng-Kung University Hospital, 138 Sheng-Li Road, Tainan, Taiwan 704.
RESUMEN
/ SUMMARY: - A 50-year-old man presented with severe
mucosal erosions of the lips, oral cavity and perianal area, a lichen
planus-like eruption on the trunk and extremities and scaly plaques of the
palms and soles. The clinical impression was of Stevens—Johnson syndrome, or
paraneoplastic pemphigus (PNP). Histopathology revealed vacuolar interface and
lichenoid dermatitis with dyskeratosis and suprabasal acantholytic
vesiculation. Direct immunofluorescence showed deposition of IgG in the
intercellular space and linear deposition of C3 along the basal membrane zone.
Indirect immunofluorescence revealed circulating IgG with intercellular
staining of the epithelium of rat urinary bladder. Western blotting
demonstrated bands of 250- and 230-kDa antigens. The clinical, histological and
immunological features were consistent with the lichen planus pemphigoides
variant of PNP. A retroperitoneal hyaline-vascular Castleman’s disease was
detected and excised. The skin lesions worsened initially after tumour
resection but improved gradually, leaving extensive melanosis after cyclosporin
and mycophenolate mofetil treatment. N.
Ref:: 21
----------------------------------------------------
[163]
TÍTULO / TITLE: - Triptolide, a novel
immunosuppressive and anti-inflammatory agent purified from a Chinese herb
Tripterygium wilfordii Hook F.
REVISTA
/ JOURNAL: - Leuk Lymphoma 2001 Jul;42(3):253-65.
AUTORES
/ AUTHORS: - Chen BJ
INSTITUCIÓN
/ INSTITUTION: - Bone Marrow Transplantation Program, Duke
University Medical Center, Box 3289, 250 Carl Building, Durham, NC 27710, USA. chen0032@mc.duke.edu.
RESUMEN
/ SUMMARY: - Triptolide is a diterpenoid triepoxide
purified from a Chinese herb Tripterygium Wilfordii Hook F (TWHF). TWHF has
been used in traditional Chinese medicine for more than two thousand years.
However, its potential value was recognized by the western medicine only after
investigators observed the effectiveness of TWHF in the treatment of leprosy
and rheumatoid arthritis. Triptolide has been identified as the major component
responsible for the immunosuppressive and anti-inflammatory effects of TWHF.
Triptolide inhibits both Ca(2+)-dependent and Ca(2+)-independent pathways and
affects T cell activation through inhibition of interleukin-2 transcription at
a site different from the target of cyclosporin A. Triptolide also has
inhibitory effects on a variety of proinflammatory cytokines and mediators and
on the expression of adhesion molecules by endothelial cells. Triptolide is effective
for the treatment of a variety of autoimmune diseases and in prevention of
allograft rejection and graft-versus-host disease in both animals and humans.
Moreover, triptolide possesses antitumor and male anti-fertility effect.
However, the toxicities of triptolide may be associated with renal, cardiac,
hematopoietic and reproductive systems. Currently available data suggest that
triptolide is a promising immunosuppressive and anti-inflammatory agent and
should be explored further in autoimmune diseases and transplantation. N. Ref:: 79
----------------------------------------------------
[164]
TÍTULO / TITLE: - First human double hand
transplantation: efficacy of a conventional immunosuppressive protocol.
REVISTA
/ JOURNAL: - Clin Transplant 2003 Oct;17(5):455-60.
AUTORES
/ AUTHORS: - Petruzzo P; Revillard JP; Kanitakis J;
Lanzetta M; Hakim NS; Lefrancois N; Owen E; Dubernard JM
INSTITUCIÓN
/ INSTITUTION: - Service de Chirurgie de Transplantation,
Hopital Edouard Herriot, Lyon, France.
RESUMEN
/ SUMMARY: - Based on the results achieved in single
human hand transplantations, we decided to perform the first double hand
transplantation with a conventional immunosuppressive protocol in a patient
with a high potential for functional recovery. Two years after transplantation
the efficacy and the safety of this immunosuppressive protocol are evaluated.
The recipient was a 33-yr-old man suffering from a traumatic amputation of both
hands in 1996. Five HLA-A, -B, and -DR mismatches were present with the donor;
T and B cell cross-match was negative. Immunosuppressive protocol included
tacrolimus, prednisone, mycophenolate mofetil and, for induction, antithymocyte
globulins and then anti CD25 monoclonal antibody. Reconstitution of lymphocyte
populations proceeded normally. Neither anti-HLA antibodies nor chimerism in
peripheral blood were detected. Two episodes of acute rejection characterized
by maculopapular lesions occurred on days 53 and 82 after transplantation. Skin
biopsies revealed a dermal lymphocytic infiltrate. Both episodes were
completely and rapidly reversed by topical clobetasol and increased systemic
corticosteroid therapy. The only side-effects related to treatment were
reversible serum sickness and hyperglycemia. No infectious complications and
malignancies occurred. No signs of graft-versus-host disease have been
detected. This case of double hand transplantation shows that conventional
immunosuppression is effective and safe to ensure survival and functional
recovery of the grafted limb.
----------------------------------------------------
[165]
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
----------------------------------------------------
[166]
TÍTULO / TITLE: - Assessing cardiovascular
risk profile of immunosuppressive agents.
REVISTA
/ JOURNAL: - Transplantation 2001 Dec 27;72(12
Suppl):S81-8.
AUTORES
/ AUTHORS: - Jardine A
N. Ref:: 57
----------------------------------------------------
[167]
TÍTULO / TITLE: - Cyclosporin for atopic
dermatitis in children.
REVISTA
/ JOURNAL: - Dermatology 2001;203(1):3-6.
AUTORES
/ AUTHORS: - Harper JI; Berth-Jones J; Camp RD; Dillon
MJ; Finlay AY; Holden CA; O’Sullivan D; Veys PA
INSTITUCIÓN
/ INSTITUTION: - Department of Paediatric Dermatology,
Great Ormond Street Hospital for Children, London, UK.
RESUMEN
/ SUMMARY: - This paper details a UK consensus
conference held in London in April 2000 to establish guidelines for the use of
cyclosporin A for atopic dermatitis in children. It should be reserved for the
severest refractory atopic dermatitis. In view of its potential toxicity,
careful monitoring is mandatory, in particular blood pressure and renal
function. N. Ref:: 4
----------------------------------------------------
[168]
TÍTULO / TITLE: - T-cell receptor-derived
peptides in immunoregulation and therapy of retrovirally induced
immunosuppression.
REVISTA
/ JOURNAL: - Crit Rev Immunol 2001;21(1-3):57-74.
AUTORES
/ AUTHORS: - Marchalonis JJ; Robey IF; Edmundson AB;
Sepulveda RT; Watson RR
INSTITUCIÓN
/ INSTITUTION: - Microbiology and Immunology, College of
Medicine, University of Arizona, Tucson 85724, USA. dianah@u.arizona.edu
RESUMEN
/ SUMMARY: - Retrovirally infected humans and mice showed
progressive acquired immunodeficiency accompanied by the production of elevated
levels of autoantibodies directed against T-cell receptor variable-domain
epitopes. Epitope mapping analyses indicated that a major determinant
recognized was defined by a 16-mer peptide containing the entire CDR1 segment
and part of the FR2 region of human Vbeta8, and that both species showed
reactivity to the same sequence. Either prophylactic or therapeutic
administration of this peptide to retrovirus-infected C57/BL/6 mice normalized
the balance of T(H)1- and T(H)2-type helper activity and restored the
resistance to infection by the opportunistic parasite Cryptosporidium.
Administration of the peptide did not generate significantly increased levels
of autoantibody, but had a profound effect on T-cell activity as well as other
aspects of inflammation, including NK-cell activity. A 16-mer derived from the
Jbeta sequence showed similar functional effects on T cells from
retrovirus-infected mice. Direct binding of the VbetaCDR1 peptide to
recombinant TCR Valpha/Vbeta constructs, as well as to IgM natural
autoantibodies, suggests that the cell surface receptor for the peptide is the
alpha/beta TCR on T cells and surface IgM in B cells. The Vbeta CDR1 peptide
stimulated division of murine splenocytes in vitro, stimulated the production
of the T(H)1 cytokine IL-2, and synergized with the T-cell mitogen concanavalin
A in proliferation and IL-2 production. These studies indicate that
administration of peptides derived from T-cell receptor variable domains to
animals immunosuppressed as a result of retroviral infection has a profound
immunomodulatory effect enhancing overall T-cell functional capacity,
particularly with respect to the cytokine production characteristic of
T(H)1-type cells. Our studies are interpreted in the context of other recent
investigations of immunomodulatory peptides.
N. Ref:: 69
----------------------------------------------------
[169]
TÍTULO / TITLE: - Current and future
applications of immunological attenuation via pegylation of cells and tissue.
REVISTA
/ JOURNAL: - BioDrugs 2001;15(12):833-47.
AUTORES
/ AUTHORS: - Chen AM; Scott MD
INSTITUCIÓN
/ INSTITUTION: - Center for Immunology and Microbial
Disease, Albany Medical College, Albany, New York, USA.
RESUMEN
/ SUMMARY: - Prevention of immunological rejection of
transplanted tissues is of crucial importance in transplantation medicine.
Current procedures primarily use pharmacological agents such as cyclosporin,
which, while effective, must be typically administered for the life of the
individual. Furthermore, the drug-induced global immunosuppression of the
patient predisposes the individual to infection and enhances their risk of
developing certain forms of cancer. Hence, additional methods are needed to
both enhance tissue engraftment and diminish the adverse effects of current
immunosuppressive therapy. Studies from blood transfusion (i.e. a specialised
form of cellular transplantation) suggest that covalent modification of cells
and tissues with methoxypoly(ethylene glycol) [mPEG] can significantly diminish
rejection episodes and may further enhance the induction of tolerance to donor
tissues. The mechanisms underlying mPEG-mediated immunocamouflage are the loss
of antigen recognition, impaired cell-cell interaction, and an inability of
endogenous antibodies (e.g. immunoglobulin G) to effectively recognise and bind
foreign epitopes. As a consequence of the global camouflage imparted by mPEG,
the weak co-stimulation of alloreactive T cells may subsequently induce
apoptosis, thus leading to tolerance. Initial studies on the transplantation of
pegylated isogeneic rat pancreatic islets demonstrates that mPEG-derivatisation
does not impair in vivo cellular signalling and function. Thus, in contrast to
the pharmacological inhibition of the recipient’s immune response, the
mPEG-mediated immunocamouflage directly addresses the inherent antigenicity and
immunogenicity of the donor tissue itself while leaving the recipient a fully
competent immune system. N.
Ref:: 43
----------------------------------------------------
[170]
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
----------------------------------------------------
[171]
TÍTULO / TITLE: - Guidelines for the
diagnosis and management of acquired aplastic anaemia.
REVISTA
/ JOURNAL: - Br J Haematol 2003 Dec;123(5):782-801.
AUTORES
/ AUTHORS: - Marsh JC; Ball SE; Darbyshire P;
Gordon-Smith EC; Keidan AJ; Martin A; McCann SR; Mercieca J; Oscier D; Roques
AW; Yin JA
INSTITUCIÓN
/ INSTITUTION: - St. George’s Hospital Medical School,
London, UK. janice@bshhya.demon.co.uk
----------------------------------------------------
[172]
TÍTULO / TITLE: - Medical management of
ulcerative colitis.
REVISTA
/ JOURNAL: - Hosp Med 2003 Dec;64(12):703-7.
AUTORES
/ AUTHORS: - Thuraisingam A; Leiper K
INSTITUCIÓN
/ INSTITUTION: - Department of Gastroenterology, Royal
Liverpool and Broadgreen University Hospitals, Liverpool L7 8XP.
RESUMEN
/ SUMMARY: - Patients with ulcerative colitis have no
increased mortality compared to population controls and the disease can be
cured be colectomy. This review concentrates on the medical management of
ulcerative colitis including the management of active colitis, acute severe
colitis and first presentation of colitis, maintenance of remission and
long-term complications. N.
Ref:: 26
----------------------------------------------------
[173]
TÍTULO / TITLE: - P-glycoprotein in acute
myeloid leukaemia: therapeutic implications of its association with both a
multidrug-resistant and an apoptosis-resistant phenotype.
REVISTA
/ JOURNAL: - Leuk Lymphoma 2002 Jun;43(6):1221-8.
AUTORES
/ AUTHORS: - Pallis M; Turzanski J; Higashi Y; Russell
N
INSTITUCIÓN
/ INSTITUTION: - Academic Haematology, Nottingham City
Hospital, Nottingham, UK. monica.pallis@nottingham.ac.uk
RESUMEN
/ SUMMARY: - P-glycoprotein (Pgp) expression is an independent
prognostic factor for response to remission-induction chemotherapy in acute
myeloblastic leukaemia, particularly in the elderly. There are several
potential agents for modulating Pgp-mediated multi-drug resistance, such as
cyclosporin A and PSC833, which are currently being evaluated in clinical
trials. An alternative therapeutic strategy is to increase the use of drugs
which are unaffected by Pgp. However, in this review, we explain why this may
be more difficult than it appears. Evidence from in vitro studies of primary
AML blasts supports the commonly held supposition that chemoresistance may be
linked to apoptosis-resistance. We have found that Pgp has a drug-independent
role in the inhibition of in vitro apoptosis in AML blasts. Modulation of cytokine
efflux, signalling lipids and intracellular pH have all been suggested as ways
by which Pgp may affect cellular resistance to apoptosis; these are discussed
in this review. For a chemosensitising agent to be successful, it may be more
important for it to enhance apoptosis than to increase drug uptake. N. Ref:: 95
----------------------------------------------------
[174]
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
----------------------------------------------------
[175]
TÍTULO / TITLE: - The potential of
antibody-based immunosuppressive agents for corneal transplantation.
REVISTA
/ JOURNAL: - Immunol Cell Biol 2003 Apr;81(2):93-105.
AUTORES
/ AUTHORS: - Thiel MA; Coster DJ; Williams KA
INSTITUCIÓN
/ INSTITUTION: - Department of Ophthalmology, Flinders
University of South Australia, Adelaide, Australia.
RESUMEN
/ SUMMARY: - Corneal transplantation is a
sight-restorative procedure but its success is limited by irreversible graft
rejection, which accounts for up to 50 per cent of failures. The normal eye is
an immune-privileged site. Multiple mechanisms maintain ocular privilege,
including the blood-eye barrier, the lack of blood vessels and lymphatics in
the normal cornea, the relative paucity of mature antigen-presenting cells in
the central cornea, the presence of immunomodulatory factors in ocular fluids,
and the constitutive expressive of CD95L (Fas ligand) within the eye. However,
privilege can be eroded by the sequelae of inflammation and neovascularization.
Corneal graft rejection in humans is currently suppressed with topical
glucocorticosteroids, which are moderately effective. Systemically administered
immunosuppressive therapy is of limited efficacy and may be accompanied by
unacceptable morbidity. Alternative therapies are needed to improve outcomes.
Corneal graft rejection is primarily a cell-mediated response controlled by the
CD4+ T cell, and thus CD4 and costimulatory molecule blockade are appealing
targets for new therapeutic interventions. A number of monoclonal antibodies
have shown promise as immunosuppressants to prolong corneal graft survival in
experimental animal models, and may eventually prove to be useful adjuncts to
corticosteroids. N.
Ref:: 205
----------------------------------------------------
[176]
TÍTULO / TITLE: - A retrospective review
of sirolimus (Rapamune) therapy in orthotopic liver transplant recipients
diagnosed with chronic rejection.
REVISTA
/ JOURNAL: - Liver Transpl 2003 May;9(5):477-83.
●●
Enlace al texto completo (gratuito o de pago) 1053/jlts.2003.50119
AUTORES
/ AUTHORS: - Neff GW; Montalbano M; Slapak-Green G;
Berney T; Bejarano PA; Joshi A; Icardi M; Nery J; Seigo N; Levi D; Weppler D;
Pappas P; Ruiz J; Schiff ER; Tzakis AG
INSTITUCIÓN
/ INSTITUTION: - University of Miami, Department of
Medicine, Miami, FL 33136, USA. gneff@med.miami.edu
RESUMEN
/ SUMMARY: - Treatment options are limited for
orthotopic liver transplant (OLT) recipients suffering from chronic rejection
(CR). We performed a retrospective review of OLT recipients diagnosed with CR
and treated with sirolimus. The medical records of all OLT recipients treated
with sirolimus between October, 1998 and October, 2000 were retrospectively
reviewed. The diagnosis of CR was made by both clinical and histologic
criteria: bile duct to hepatic artery ratio less than 0.7, histologic activity
index, hepatic arterial wall thickening, and chronic elevation of liver
chemistries. Two groups were defined in regard to sirolimus response: sirolimus
responders (SR) and sirolimus nonresponders (SNR). Response to treatment was
granted only when patients were found to have resolution of abnormal liver
transaminases and an improvement in hepatic artery to bile duct ratio. Serum
collections for liver chemistries were collected on days 1, 30, 60, and 90.
Liver biopsies were reviewed in blinded fashion from day 1 and at least 180
days on therapy by double-blinded pathologists. Sirolimus-related complications
were recorded and include drug toxicity, anemia with and without treatment,
hospitalizations, infections, immunosuppression complications, lipid profile
disorders, edema, muscle aches, and gastrointestinal complaints. Twenty-one
patients were diagnosed with CR. The SR group included 13 of 21, and 8 of 21
were in the SNR group. Anemia was diagnosed in 12 of 21 patients: SR, 7 of 13;
SNR, 5 of 8; with 5 patients requiring red blood cell transfusions (2 SR, 3
SNR). Recombinant erythropoietin was started in 5 of 21 patients. Sirolimus
serum levels were found to be greater than 20 ng/dL in 12 patients. Sirolimus
was discontinued in 9 patients,
----------------------------------------------------
[177]
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.
----------------------------------------------------
[178]
TÍTULO / TITLE: - Transition from
methotrexate and cyclosporine to other therapies including retinoids,
ultraviolet light and biologic agents in the management of patients with
psoriasis.
REVISTA
/ JOURNAL: - J Dermatolog Treat 2003;14 Suppl 2:7-16.
AUTORES
/ AUTHORS: - Maryles S; Rozenblit M; Lebwohl M
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology, Mount Sinai
School of Medicine, 1 Gustave Levy Place, New York, NY 10029-6574, USA.
RESUMEN
/ SUMMARY: - Patients with psoriasis typically face
longterm therapy for their chronic disease. Often, the therapeutic agents that
physicians use to treat them may become less effective or may cause safety or
toxicity issues. The clinician must then decide the next therapy for his/her
patient and assess benefit/risk of the next therapeutic agent or combination.
In moving the patient from one therapy to the next, specific characteristics of
the transition must be assessed, and how to stop the existing therapy, and
introduce the new agent(s). The decision making process must take into account
the longterm risks to the patient. This article focuses on the transition for
patients with psoriasis being managed with methotrexate and cyclosporine to
retinoids, phototherapy, and newer agents.
N. Ref:: 97
----------------------------------------------------
[179]
TÍTULO / TITLE: - Effects of tacrolimus
on ischemia-reperfusion injury.
REVISTA
/ JOURNAL: - Liver Transpl 2003 Feb;9(2):105-16.
●●
Enlace al texto completo (gratuito o de pago) 1053/jlts.2003.50020
AUTORES
/ AUTHORS: - St
Peter SD; Moss AA; Mulligan DC
INSTITUCIÓN
/ INSTITUTION: - Department of Transplant Surgery, Mayo
Clinic Scottsdale, AZ, USA.
RESUMEN
/ SUMMARY: - In addition to efficacious
immunosuppression for the benefit of organ transplantation, tacrolimus has
diverse actions that result in amelioration of ischemia-reperfusion injury.
Knowledge is accumulating rapidly on the mechanisms through which tacrolimus
exerts these cytoprotective effects, including alterations in microcirculation,
free radical metabolism, calcium-activated pathways, inflammatory cascades,
mitochondrial stability, apoptosis, stress-response proteins, and tissue
recovery. Within the nucleus, actions mediating the effects of tacrolimus
appear to be dominantly influenced by interactions with the transcription
factor, nuclear factor-kappaB. Because tacrolimus is a cornerstone agent in
immunosuppression regimens throughout the world and knowledge of its cellular
mechanisms is evolving, it is important to update the clinical literature with
this information. We reviewed the published literature with intent to portray
the interactions of tacrolimus in the intricate cellular mechanisms initiated
by ischemia and reperfusion. N.
Ref:: 122
----------------------------------------------------
[180]
TÍTULO / TITLE: - Combining the new
biologic agents with our current psoriasis armamentarium.
REVISTA
/ JOURNAL: - J Am Acad Dermatol 2003 Aug;49(2
Suppl):S118-24.
AUTORES
/ AUTHORS: - Lebwohl M
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology, Mount Sinai
School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA. sinaiderm@aol.com
RESUMEN
/ SUMMARY: - Combination therapy, rotational therapy,
and sequential therapy have been used for psoriasis in attempts to achieve
greater efficacy and greater safety. The purpose of this manuscript is to
review potential advantages and disadvantages of new biologic agents as we look
forward to their use in combination regimens with other systemic, topical, and
light therapies. Data on the efficacy and toxicity of existing systemic
therapies and new biologic agents is reviewed with an emphasis on potential
additive or synergistic benefits or toxicities. The mechanism of action of
biologic agents differs from systemic agents currently in use, suggesting that
there may be additive effects in treating psoriasis. The absence of
hepatotoxicity and nephrotoxicity are important advantages when considering
combination therapy with biologic agents. The advantages of the use of biologic
therapies in combination or rotation with other systemic agents will have to be
demonstrated in clinical trials. Mechanisms of action of the biologic therapies
suggest that there is potential for additive benefit when used in combination
regimens. N. Ref:: 45
----------------------------------------------------
[181]
TÍTULO / TITLE: - A pilot protocol of a
calcineurin-inhibitor free regimen for kidney transplant recipients of marginal
donor kidneys or with delayed graft function.
REVISTA
/ JOURNAL: - Clin Transplant 2003;17 Suppl 9:31-4.
AUTORES
/ AUTHORS: - Shaffer D; Langone A; Nylander WA; Goral
S; Kizilisik AT; Helderman JH
INSTITUCIÓN
/ INSTITUTION: - Department of Surgery, Vanderbilt University
Medical Center, Nashville, TN 37232, USA. david.schaffer@vanderbilt.edu
RESUMEN
/ SUMMARY: - The worsening shortage of cadaver donor
kidneys has prompted use of expanded or marginal donor kidneys (MDK), i.e.
older age or donor history of hypertension or diabetes. MDK may be especially
susceptible to calcineurin-inhibitor (CI) mediated vasoconstriction and
nephrotoxicity. Similarly, early use of CI in patients with delayed graft
function may prolong ischaemic injury. We developed a CI-free protocol of
antibody induction, sirolimus, mycophenolate mofetil, and prednisone in
recipients with MDK or DGF. METHODS: Adult renal transplant recipients who
received MDK or had DGF were treated with a CI-free protocol consisting of
antibody induction (basiliximab or thymoglobulin), sirolimus, mycophenolate
mofetil, and prednisone. Serial biopsies were performed for persistent DGF.
Patients were followed prospectively with the primary endpoints being patient
and graft survival, biopsy-proven acute rejection, and sirolimus-related
toxicity. RESULTS: Nineteen recipients were treated. Mean follow-up was 294
days. Actuarial 6- and 12-month patient survival was 100% and 100% and graft
survival was 93% and 93%, respectively. The only graft loss was due to primary
non-function (PNF). The incidence of AR was 16%. Mean serum creatinine at last
follow-up was 1.6 mg/dL. Sirolimus-related toxicity included lymphocele (1),
wound infection (2), thrombocytopenia (1). and interstitial pneumonitis (1).
CONCLUSION: A CI-free protocol with antibody induction and sirolimus results in
low rates of AR and PNF and excellent early patient and graft survival in
patients with MDK and DGF. CI-free protocols may allow expansion of the kidney donor
pool by encouraging utilization of MDK at high risk for DGF or CI-mediated
nephrotoxicity.
----------------------------------------------------
[182]
TÍTULO / TITLE: - Potential role of
immune modulation in the effective long-term control of HIV-1 infection.
REVISTA
/ JOURNAL: - J Biol Regul Homeost Agents 2002
Jan-Mar;16(1):83-90.
AUTORES
/ AUTHORS: - Rizzardi GP; Lazzarin A; Pantaleo G
INSTITUCIÓN
/ INSTITUTION: - MOLMED, Milan, Italy. paolo.rizzardi@molmed.it
RESUMEN
/ SUMMARY: - Recent advances in HIV-1 pathogenesis, and
in defining virological and immunological responses to highly active
antiretroviral therapy (HAART), along with the identification of the numerous
drawbacks of HAART, have clearly demonstrated that the eradication of the virus
is not a feasible therapeutic goal, and that there is an urgent need to develop
other approaches to fight HIV-1 infection. Novel therapeutic approaches of
immune modulation have recently been evaluated in pilot clinical trials. First,
treating primary HIV-1 infection with cyclosporin A (CsA) coupled with HAART to
target massive immune activation extends the benefits achieved with HAART
during primary HIV-1 infection and might contribute to the establishment of a
more favourable immunological set-point affecting the ultimate pattern and rate
of disease progression. Second, treating chronic HIV-1 infection in patients
with long-term suppression of virus replication induced by HAART, with the
addition of mycophenolate mofetil (MMF) reduces the pool of activated CD4+ T
lymphocytes able to support productive HIV-1 infection, and might have an
indirect impact on the pool of resting, latently infected CD4+ T cells,
contributing to its depletion in vivo. The important question is clearly
whether these results will have an impact on the clinical management of
patients with HIV-1 infection, determining the precise therapeutic function of
drugs like CsA and MMF, thus investigating the effects of these drugs on
residual viral replication and the decay of the latent reservoir, on long-term
immunological benefit, and, ultimately, on clinical benefit. N. Ref:: 95
----------------------------------------------------
[183]
TÍTULO / TITLE: - Review article: medical
treatment of severe ulcerative colitis.
REVISTA
/ JOURNAL: - Aliment Pharmacol Ther 2002 Jul;16 Suppl
4:7-12.
AUTORES
/ AUTHORS: - Daperno M; Sostegni R; Rocca R; Rigazio C;
Scaglione N; Castellino F; Ercole E; Pera A
INSTITUCIÓN
/ INSTITUTION: - U.O.A. Di Gastroenterologia, Ospedale
Mauriziano Umberto I, Torino, Italy.
RESUMEN
/ SUMMARY: - Approximately 15% of patients with
ulcerative colitis have a severe attack requiring hospitalization at some time
during their illness. This treatment leads to a remission in 60-80% of patients
and non-responders may require a total colectomy. Mortality in severe episodes
of ulcerative colitis decreased from 31-61% in the 1950s to 5-9% in the 1960s
thanks to the introduction of steroids and to a policy of early colectomy.
Recently, some new drugs have been shown to be effective in the treatment of
severe steroid-refractory ulcerative colitis. This review concentrates on the
clinical evaluation, prognostic factors and new developments in medical therapy
in severe ulcerative colitis. A retrospective evaluation of a consecutive
series of patients with severe ulcerative colitis admitted to a
Gastroenterology Department in Torino, Italy, is also reported. N. Ref:: 37
----------------------------------------------------
[184]
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
----------------------------------------------------
[185]
TÍTULO / TITLE: - Extragonadal seminoma
after renal transplantation and immunosuppression; treatment in the presence of
renal dysfunction: a case report and literature review.
REVISTA
/ JOURNAL: - Med Oncol 2001;18(3):221-5.
AUTORES
/ AUTHORS: - Kosmas C; Tsavaris NB; Vadiaka M; Chiras
T; Boletis J; Kostakis A
INSTITUCIÓN
/ INSTITUTION: - Department of Pathophysiology, Athens
University School of Medicine, Laikon General Hospital, Greece. ckosm@ath.forthnet.gr
RESUMEN
/ SUMMARY: - A 37-yr-old man who had undergone renal
transplantation for end-stage renal failure presented with a large right pelvic
mass obstructing the transplanted kidney. Initially, this was diagnosed as an
anaplastic tumor while he had been on immunosuppressive treatment for kidney
allograft rejection after transplantation. Despite difficulties of classic
histopathology to reveal the origin of his tumor, FISH analysis revealed the
presence of chromosome 12p abnormalities, strongly indicative of a germ-cell
tumor-more likely seminoma-with extragonadal presentation. Because of renal
dysfunction, he was treated with carboplatin (dose adjusted according to renal
clearance) and etoposide, and when he experienced a rather atypical progression
with bone metastases, he was treated with single-agent paclitaxel, and died
almost 13 mo after initial presentation. The case adds further to the existing
small list of seminoma/GCTs developing in transplant recipients, points to the
unusual presentation patterns and diagnostic histopathology challenges, and
presents the difficulty in therapeutic options, as a result of frequent renal
dysfunction and intercurrent immunosuppressive therapy. All of these issues
together with an extensive literature review are discussed in detail.
----------------------------------------------------
[186]
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
----------------------------------------------------
[187]
TÍTULO / TITLE: - Persistent remission
after immunosuppressive therapy of hairy cell leukemia mimicking aplastic
anemia: two case reports.
REVISTA
/ JOURNAL: - Int J Hematol 2003 May;77(4):391-4.
AUTORES
/ AUTHORS: - Sugimori C; Kaito K; Nakao S
INSTITUCIÓN
/ INSTITUTION: - Cellular Transplantation Biology, Kanazawa
University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.
RESUMEN
/ SUMMARY: - Some patients with hairy cell leukemia
(HCL) manifest pancytopenia and bone marrow hypoplasia without an apparent
increase in atypical cells, so their disease resembles severe aplastic anemia
at onset. We treated 2 HCL patients, who were initially diagnosed with aplastic
anemia, with antithymocyte globulin (ATG) in combination with cyclosporine or
antilymphocyte globulin (ALG). Both patients obtained partial remission in
response to the immunosuppressive therapy and did not need transfusion treatment
for more than 3 years. Sustained improvement of hematopoiesis in such B-cell
malignancies after ATG/ ALG therapy suggests that the mechanisms underlying
successful immunosuppressive therapy for aplastic anemia may involve B-cell
suppression, inhibiting hematopoietic stem cells. N. Ref:: 18
----------------------------------------------------
[188]
TÍTULO / TITLE: - Immunophilins in
nervous system degeneration and regeneration.
REVISTA
/ JOURNAL: - Curr Top Med Chem 2003;3(12):1376-82.
AUTORES
/ AUTHORS: - Avramut M; Achim CL
INSTITUCIÓN
/ INSTITUTION: - Department of Pathology, School of
Medicine, University of Pittsburgh, S-433 Biomedical Science Tower, 200 Lothrop
Street, Pittsburgh, PA 15213, USA. avramut@pitt.edu
RESUMEN
/ SUMMARY: - Immunophilins are receptors for
immunosuppressive drugs like cyclosporin A, FK506, rapamycin and their non-
immunosuppressive analogs, which are collectively referred to as “immunophilin
ligands” (IPL). Cyclosporin A binds to a class of IP called cyclophilins,
whereas the receptors for FK506 and rapamycin belong to the family of FK506-
binding proteins (FKBP). The latter are designated according to their molecular
weight: FKBP12, 25, 52 etc. FKBP levels in the rat brain are up to 50 times
higher than in the immune system. FKBP12 is associated with IP3 and ryanodine
receptors present on the endoplasmic reticulum and plays a role in stabilizing
calcium release. It has also been proposed to be a modulator of the TGFbeta receptor
activity. Crush injury of facial or sciatic nerves in rat leads to markedly
increased FKBP12 levels in the respective nerve nuclei and this increase is
related to nerve regeneration. Cyclophilin A protects cells from death
following expression of mutant Cu/ Zn superoxide dismutase, which is associated
with familial amyotrophic lateral sclerosis. Our recent studies show that
FKBP12 and FKBP52 are expressed in the human nervous system, especially in the
substantia nigra- deep gray matter axis. In neurodegenerative diseases, FKBP12
levels increase in neurons situated in areas of pathology. This IP colocalizes
with synaptophysin and alpha- synuclein, suggesting that it may become a novel
marker of pathology. Immunophilins participate in axonal transport, synaptic
vesicle assembly and may play a role in neuroprotection against abnormal
protein aggregation, suggesting a potential avenue of therapeutic
interventions. N.
Ref:: 62
----------------------------------------------------
[189]
TÍTULO / TITLE: - Rapamycin in
combination with cyclosporine or tacrolimus in liver, pancreas, and kidney
transplantation.
REVISTA
/ JOURNAL: - Transplant Proc 2003 May;35(3
Suppl):201S-208S.
AUTORES
/ AUTHORS: - MacDonald AS
INSTITUCIÓN
/ INSTITUTION: - Department of Surgery, Dalhousie
University, Halifax, Nova Scotia, Canada. Allan.macdonald@dal.ca
RESUMEN
/ SUMMARY: - A 10-year experience with the
immunosuppressive drug rapamycin that begins in the laboratory then extends through
multicentre trials in combination with cyclosporine in kidney transplant
recipients, exploration of its use as a single agent and in combination with
tacrolimus, and its potential in nonrenal organs is described. Rapamycin is a
potent inhibitor of endothelial injury in rat aortic allografts. When added to
full-dose cyclosporine it achieves low rejection rates, but it augments the
nephrotoxicity and hyperlipidemia of cyclosporine. On the other hand, it allows
discontinuation of calcineurin inhibitors in stable kidney and liver patients
suffering from nephrotoxicity late posttransplant. At least in Caucasian
patients, discontinuation of cyclosporine is possible as early as 3 months
post-kidney transplant. In combination with low-dose tacrolimus, exceptionally
low rates of rejection were seen in recipients of kidney, pancreas, and liver
recipients with preservation of excellent renal function. These pilot studies
have been confirmed in several single-centre and, more recently, multicentre
trials in kidney and pancreas transplantation. The side-effect profile of
hyperlipidemia, lymphocoeles, delayed wound healing, and possible liver effects
are coming into focus, and ways of minimizing these problems being introduced.
The lessons learned include the need for early adequate blood levels, the lack
of correlation between dose and drug exposure, and the potency that allows
marked dose reductions in calcineurin inhibitors and steroids. N. Ref:: 36
----------------------------------------------------
[190]
TÍTULO / TITLE: - Current systemic
therapies for psoriasis: where are we now?
REVISTA
/ JOURNAL: - J Am Acad Dermatol 2003 Aug;49(2
Suppl):S66-77.
●●
Enlace al texto completo (gratuito o de pago) 1016/mjd.2003.550
AUTORES
/ AUTHORS: - Yamauchi PS; Rizk D; Kormeili T; Patnaik
R; Lowe NJ
INSTITUCIÓN
/ INSTITUTION: - Clinical Research Specialists, UCLA School
of Medicine, 2001 Santa Monica Boulevard, Santa Monica, CA 90404, USA.
RESUMEN
/ SUMMARY: - Many systemic agents are used in the
treatment of psoriasis. They provide good control of psoriasis in the majority
of patients and have improved their life quality indices. Frequently,
combination therapy is utilized to synergize the efficacy of these medications.
Many dermatologists are hesitant in prescribing systemic agents because of
their adverse effects. However, such potential toxicities arising from these
medications can largely be avoided if proper patient selection and close
monitoring are performed. N.
Ref:: 83
----------------------------------------------------
[191]
TÍTULO / TITLE: - Treatment of atopic
dermatitis and impact on quality of life: a review with emphasis on topical
non-corticosteroids.
REVISTA
/ JOURNAL: - Pharmacoeconomics 2003;21(3):159-79.
AUTORES
/ AUTHORS: - Schiffner R; Schiffner-Rohe J; Landthaler
M; Stolz W
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology, University of
Regensburg, Regensburg, Germany. jr.schiffner@t-online.de
RESUMEN
/ SUMMARY: - Atopic dermatitis (AD) is a chronic skin
disease with increasing prevalence and rising costs. Stigmatisation and
pruritus are only some aspects of potential quality-of-life (QOL) impairments.
AD is not curable and repeated treatments are often necessary. At present,
treatment with topically-applied corticosteroids is state-of-the-art for mild
to moderate flare-ups. However, many patients are worried about the use of
corticosteroids due to the widespread fear of adverse effects. In this review
the present literature is analysed concerning impact on quality of life for
topically-applicable alternatives to the state-of-the-art treatment. For
comparison reasons, data from other treatment modalities are additionally
given. Characteristics of studies were analysed using ‘general’ (year and mode
of publication, type and aim of study, number of patients, and clinical measurement)
and ‘QOL specific’ criteria (type and number of QOL measurements including
relevance for study aim and age group, validation in used language, sensitivity
to change, and improvement at end of study). QOL data are published only in the
minority of studies evaluating treatment efficacy and do not cover the variety
of possible therapies. Data are available for tacrolimus, pimecrolimus, UVA/UVB
combination and UVB narrowband (topical non-corticosteroidal treatments), as
well as for topical corticosteroids, cyclosporin, and inpatient treatment. All
studies provided a marked improvement in quality of life after therapy. One
study assessed quality of life after a treatment-free follow-up period
obtaining a clear increase in impact on quality of life. Since studies used
different QOL measurements and vary in inclusion criteria, treatment schedules
and presentation of results, a comparison of QOL improvement is not
recommended. A single randomised study compared topically applied
non-corticosteroidal treatment (UVA/UVB combination) with another treatment
modality (cyclosporin) and found no difference in QOL improvement. At present,
there is a clear lack of controlled randomised studies evaluating different
active treatment modalities and their impact on quality of life. Consensus
meetings are desirable to formulate guidelines for the selection and correct
use of QOL measurements. Patients’ fear of side effects (e.g. concerning
corticosteroids) should be integrated in QOL questionnaires for evaluation of
possible compliance problems and real costs. Since relapse after treatment is
frequent in AD, QOL measurements should also be performed after a
treatment-free follow-up period. At present, we can not answer the question
‘which treatment best improves quality of life in AD?’. N. Ref:: 128
----------------------------------------------------
[192]
TÍTULO / TITLE: - Cardiac allograft
vasculopathy: current concepts and treatment.
REVISTA
/ JOURNAL: - Transpl Int 2003 Jun;16(6):367-75. Epub
2003 May 17.
●●
Enlace al texto completo (gratuito o de pago) 1007/s00147-003-0580-8
AUTORES
/ AUTHORS: - Waller J; Brook NR; Nicholson ML
INSTITUCIÓN
/ INSTITUTION: - Division of Transplant Surgery, Professorial
Unit, Leicester General Hospital, Leicester, Leicestershire, UK. julian@waller720.fsnet.co.uk
RESUMEN
/ SUMMARY: - Cardiac allograft vasculopathy (CAV)
remains the leading limiting factor of patient and graft survival after the
first post-operative year. The pathogenesis involves both immunological and
non-immunological factors. Here, we present recent advances and discuss
potential preventative and treatment regimens. A review of the current literature
of heart transplantation, detailing molecular mechanisms, pharmacological risk
factors and novel immunosuppression regimens was performed. Recent findings
demonstrate the pivotal role of the endothelium, resulting in release of
pro-fibrotic cytokines, recruitment of circulating leucocytes, proliferation of
vascular smooth muscle cells, and deposition of extracellular matrix proteins
(ECMs). The role of HMG-CoA reductase inhibitors and anti-hypertensives remains
controversial, but there is increasing evidence advocating their prophylactic
use. We can conclude that novel immunosuppressive agents such as rapamycin,
mycophenolate mofetil and FTY-720 are experimental immunosuppressive agents
that are undergoing evaluation in clinical trials. The prophylactic use of
statins and anti-hypertensive drugs needs to be defined but needs to suggest
potential strategies to prolong cardiac allograft survival. N. Ref:: 102
----------------------------------------------------
[193]
TÍTULO / TITLE: - The evolving role of
sirolimus in renal transplantation.
REVISTA
/ JOURNAL: - Qjm. Acceso gratuito al texto completo a
partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://qjmed.oupjournals.org/
●●
Cita: QJM: <> 2003 Jun;96(6):401-9.
AUTORES
/ AUTHORS: - Dupont P; Warrens AN
INSTITUCIÓN
/ INSTITUTION: - Division of Medicine, Imperial College
London, London, UK. N.
Ref:: 66
----------------------------------------------------
[194]
TÍTULO / TITLE: - Transplant
immunosuppressant agents and their role in autoimmune rheumatic diseases.
REVISTA
/ JOURNAL: - Curr Opin Rheumatol 2003 May;15(3):219-25.
AUTORES
/ AUTHORS: - Mayer DF; Kushwaha SS
INSTITUCIÓN
/ INSTITUTION: - Division of Rheumatology, Mayo Clinic and
Mayo Foundation, Rochester, Minnesota, USA.
RESUMEN
/ SUMMARY: - This article examines immunosuppressant
transplant agents used to treat the various rheumatic diseases. The older drugs
of this type have been used in this dual role for decades. There is a new
generation of immunosuppressant drugs with established use in the arena of
transplantation medicine. Only recently have the potential rheumatologic
applications for these agents been investigated. The authors review in depth
the published experience with the newer agents. The authors also discuss novel
rheumatologic uses for the older agents that have been described within the
past year. N. Ref:: 59
----------------------------------------------------
[195]
TÍTULO / TITLE: - St John’s Wort
supplements endanger the success of organ transplantation.
REVISTA
/ JOURNAL: - Arch Surg 2002 Mar;137(3):316-9.
AUTORES
/ AUTHORS: - Ernst E
INSTITUCIÓN
/ INSTITUTION: - Department of Complementary Medicine,
School of Sport and Health Sciences, University of Exeter, 25 Victoria Park Rd,
Exeter EX2 4NT, England. E.Ernst@ex.ac.uk
RESUMEN
/ SUMMARY: - HYPOTHESIS: St John’s wort is one of the
most popular herbal medicines, and health care professionals often are unaware
that their patients take such supplements. St John’s wort causes a decrease in
cyclosporine levels, thus endangering the success of organ transplantations.
DESIGN: Systematic review. METHODS: Five independent computerized literature
searches were conducted to identify all reports of such interactions. Data were
extracted and are summarized in narrative form. RESULTS: Eleven case reports
and 2 case series were located. In most instances, causality between St John’s
wort and the clinical or biochemical result is well established. The mechanism
of interaction between St John’s wort and cyclosporine has been recently
elucidated and involves both P-glycoprotein and cytochrome P 450 3A4
expression. Collectively these data leave little doubt that St John’s wort
interacts with cyclosporine, causing a decrease of cyclosporine blood levels
and leading in several cases to transplant rejection. CONCLUSIONS: St John’s
wort can endanger the success of organ transplantations. Adequate information
may be the best way to avoid future incidences. N. Ref:: 33
----------------------------------------------------
[196]
TÍTULO / TITLE: - Sirolimus and
mycophenolate mofetil for calcineurin-free immunosuppression in renal
transplant recipients.
REVISTA
/ JOURNAL: - Am J Kidney Dis 2001 Oct;38(4 Suppl
2):S16-21.
AUTORES
/ AUTHORS: - Pescovitz MD; Govani M
INSTITUCIÓN
/ INSTITUTION: - Departments of Surgery,
Microbiology/Immunology, and Medicine, Indiana University, Indianapolis, IN
46202, USA. mpescov@iupui.edu
RESUMEN
/ SUMMARY: - Calcineurin inhibitors, such as
cyclosporine and tacrolimus, have been available for almost 20 years. Although
these drugs are highly effective and represent the mainstay of transplant
immunosuppression, they are associated with acute and chronic nephrotoxicity.
Acute nephrotoxicity, which occurs in the early period after transplantation,
leads to a higher rate of dialysis, and chronic nephrotoxicity may eventually
result in graft loss. Acute and chronic nephrotoxicity is becoming more common
as the use of marginal kidneys for transplantation increases. Two recently
available immunosuppressive agents, mycophenolate mofetil and sirolimus
(rapamycin), have no nephrotoxicity. The use of these drugs in combination with
other agents has led to the development of new paradigms of immunosuppressive
therapy. This paper reviews the results of clinical trials that have
investigated these new approaches to immunosuppression in renal transplant recipients. N. Ref:: 9
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[197]
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
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[198]
TÍTULO / TITLE: - Inflammatory bowel
disease: sorting out the treatment options.
REVISTA
/ JOURNAL: - Cleve Clin J Med. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.ccjm.org/
●●
Cita: Cleveland Clinic J. of Medicine: <> 2002 Aug;69(8):621-6, 629-31.
AUTORES
/ AUTHORS: - Wolf JM; Lashner BA
INSTITUCIÓN
/ INSTITUTION: - Department of Gastroenterology, The
Cleveland Clinic Foundation, Ohio 44195, USA.
RESUMEN
/ SUMMARY: - An increasing array of treatments such as
immunosuppressive drugs and tumor necrosis factor inhibitors can offer patients
with ulcerative colitis and Crohn disease improved relief from symptoms with
fewer adverse effects. Several additional drugs have shown promise, including
nicotine, antimicrobials, and heparin. N.
Ref:: 59
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[199]
TÍTULO / TITLE: - St John’s wort
(Hypericum perforatum): drug interactions and clinical outcomes.
REVISTA
/ JOURNAL: - Br J Clin Pharmacol 2002 Oct;54(4):349-56.
AUTORES
/ AUTHORS: - Henderson L; Yue QY; Bergquist C; Gerden
B; Arlett P
INSTITUCIÓN
/ INSTITUTION: - Pharmacovigilance Group, Medicines Control
Agency, UK. leigh.henderson@mca.gsi.gov.uk
RESUMEN
/ SUMMARY: - AIMS: The aim of this work is to identify
the medicines which interact with the herbal remedy St John’s wort (SJW), and
the mechanisms responsible. METHODS: A systematic review of all the available
evidence, including worldwide published literature and spontaneous case reports
provided by healthcare professionals and regulatory authorities within Europe
has been undertaken. RESULTS: A number of clinically significant interactions
have been identified with prescribed medicines including warfarin,
phenprocoumon, cyclosporin, HIV protease inhibitors, theophylline, digoxin and
oral contraceptives resulting in a decrease in concentration or effect of the
medicines. These interactions are probably due to the induction of cytochrome
P450 isoenzymes CYP3A4, CYP2C9, CYP1A2 and the transport protein P-glycoprotein
by constituent(s) in SJW. The degree of induction is unpredictable due to
factors such as the variable quality and quantity of constituent(s) in SJW
preparations. In addition, possible pharmacodynamic interactions with selective
serotonin re-uptake inhibitors and serotonin (5-HT(1d)) receptor-agonists such
as triptans used to treat migraine were identified. These interactions are
associated with an increased risk of adverse reactions. CONCLUSIONS: In Sweden
and the UK the potential risks to patients were judged to be significant and
therefore information about the interactions was provided to health care
professionals and patients. The product information of the licensed medicines
involved has been amended to reflect these newly identified interactions and
SJW preparations have been voluntarily labelled with appropriate warnings. N. Ref:: 44
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[200]
TÍTULO / TITLE: - Treatment of
gammaherpesvirus-related neoplastic disorders in the immunosuppressed host.
REVISTA
/ JOURNAL: - Semin Hematol 2003 Apr;40(2):163-71.
●●
Enlace al texto completo (gratuito o de pago) 1053/shem.2003.50016
AUTORES
/ AUTHORS: - Little RF; Yarchoan R
INSTITUCIÓN
/ INSTITUTION: - HIV and AIDS Malignancy Branch, Center for
Cancer Research, National Cancer Institute, National Institutes of Health,
Bethesda, MD 20892, USA.
RESUMEN
/ SUMMARY: - Neoplastic disease is a frequent
complication in patients with acquired immunodeficiency disease (AIDS) and
other immunodeficiencies. Many such neoplasms are caused by either Epstein-Barr
virus (EBV) or Kaposi’s sarcoma-associated herpes virus (KSHV). The treatment
of such patients can be challenging. At the same time, the viral origin of
these tumors offers targets to develop pathogenesis-based therapies. Standard
therapies for these diseases involve such approaches as treating the underlying
immunodeficiency, cytotoxic chemotherapy, and immunologic antitumor therapy.
Novel therapy approaches include specific immune therapy and anti-angiogenesis approaches,
now under development. N.
Ref:: 105
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