#03#
Revisiones-Clínica-Etiología
& Patología *** Reviews-Clinical-Etiology & Pathology
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
La
biblioteca del conocimiento biomédico© es un servicio GRATUITO. Toda la
información ha sido obtenida de fuentes públicas, de portales de internet que
no requieren registro alguno para su uso, que no requieren estar de acuerdo con
sus Términos de uso, que son de libre acceso a todo el mundo, y son a su vez
gratuitos. La biblioteca (revisiones, guías, protocolos, medicina basada en la
evidencia, etc...) se recopila en base a una patente que permite a Effiloop la catalogación
de los artículos por campos de interés así como por el orden de su importancia
(se proveen las primeras 200 revisiones). Toda la informacion se ampara en las
leyes de libre pensamiento-expresión, y de uso justo. Este documento sólo
contiene artículos escritos en Castellano y/o Inglés.
The
biomedical library© is a FREE service. All the information has been obtained
from public sources, from web sites that do not require registration for their
use, that do not require an agreement with their Terms of use, that provide
free access for all, and are free of charge. The library (reviews, guides,
protocols, medicine based medicine, etc) is arranged according to a patent that
warrants Effiloop to catalogue the articles by fields of interest as well as to
sort articles by true relevance (the first 200 reviews are provided). All the
information is provided according to the freedom of speech and fair use laws.
Only articles written in Spanish and/or English are included.
[1]
TÍTULO / TITLE: - Integration of growth
factor and nutrient signaling: implications for cancer biology.
REVISTA
/ JOURNAL: - Mol Cell 2003 Aug;12(2):271-80.
AUTORES
/ AUTHORS: - Shamji AF; Nghiem P; Schreiber SL
INSTITUCIÓN
/ INSTITUTION: - Harvard Biophysics Program, Harvard
University, 12 Oxford Street, Cambridge, MA 02138, USA.
RESUMEN
/ SUMMARY: - Signaling networks that promote cell
growth are frequently dysregulated in cancer. One regulatory network, which
converges on effectors such as 4EBP1 and S6K1, leads to growth by promoting
protein synthesis. Here, we discuss how this network is regulated by both
extracellular signals, such as growth factors, and intracellular signals, such
as nutrients. We discuss how mutations amplifying either type of signal can
lead to tumor formation. In particular, we focus on the recent discovery that a
tumor suppressor complex whose function is lost in tuberous sclerosis patients
regulates the nutrient signal carried by the critical signaling protein TOR to
the effectors 4EBP1 and S6K1. Finally, we describe how the small molecule
rapamycin, which inhibits TOR and thereby the activation of these effectors,
could be useful to treat tumors that have become dependent upon this pathway
for growth. N. Ref:: 80
----------------------------------------------------
[2]
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
----------------------------------------------------
[3]
- 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
----------------------------------------------------
[4]
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.
----------------------------------------------------
[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: - 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
----------------------------------------------------
[8]
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
----------------------------------------------------
[9]
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
----------------------------------------------------
[10]
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
----------------------------------------------------
[11]
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.
----------------------------------------------------
[12]
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
----------------------------------------------------
[13]
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
----------------------------------------------------
[14]
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
----------------------------------------------------
[15]
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
----------------------------------------------------
[16]
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
----------------------------------------------------
[17]
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
----------------------------------------------------
[18]
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.
----------------------------------------------------
[19]
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
----------------------------------------------------
[20]
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
----------------------------------------------------
[21]
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
----------------------------------------------------
[22]
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
----------------------------------------------------
[23]
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
----------------------------------------------------
[24]
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
----------------------------------------------------
[25]
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
----------------------------------------------------
[26]
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.
----------------------------------------------------
[27]
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
----------------------------------------------------
[28]
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
----------------------------------------------------
[29]
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
----------------------------------------------------
[30]
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
----------------------------------------------------
[31]
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
----------------------------------------------------
[32]
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
----------------------------------------------------
[33]
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.
----------------------------------------------------
[34]
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
----------------------------------------------------
[35]
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
----------------------------------------------------
[36]
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.
----------------------------------------------------
[37]
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
----------------------------------------------------
[38]
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
----------------------------------------------------
[39]
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.
----------------------------------------------------
[40]
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
----------------------------------------------------
[41]
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
----------------------------------------------------
[42]
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
----------------------------------------------------
[43]
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.
----------------------------------------------------
[44]
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
----------------------------------------------------
[45]
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
----------------------------------------------------
[46]
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
----------------------------------------------------
[47]
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
----------------------------------------------------
[48]
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
----------------------------------------------------
[49]
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.
----------------------------------------------------
[50]
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
----------------------------------------------------
[51]
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
----------------------------------------------------
[52]
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
----------------------------------------------------
[53]
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
----------------------------------------------------
[54]
TÍTULO / TITLE: - Tissue factor and
coronary artery disease.
REVISTA
/ JOURNAL: - Cardiovasc Res 2002 Feb 1;53(2):313-25.
AUTORES
/ AUTHORS: - Moons AH; Levi M; Peters RJ
INSTITUCIÓN
/ INSTITUTION: - Department of Cardiology, Academic Medical
Center, Room F3-236, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
RESUMEN
/ SUMMARY: - Plaque disruption with superimposed
thrombosis is the main cause of acute coronary events such as acute myocardial
infarction and unstable angina. Among other factors, tissue factor seems to
play an important role determining plaque thrombogenicity. Tissue factor is a
potent initiator of the coagulation cascade situated within the vessel wall and
is highly exposed to the blood after plaque rupture. Several mediators involved
in the process of atherosclerotic plaque formation are capable of inducing
tissue factor expression in cells such as monocytes, macrophages and
endothelial cells, which under normal conditions do not express tissue factor
or to a limited extent only. The increased expression of tissue factor is not
limited to the plaque but is also found in circulating monocytes in patients
with acute coronary syndromes. In addition, studies have shown an important
contribution of tissue factor in the pathogenesis of thrombosis and restenosis
after balloon angioplasty. Recent basic studies focus on the therapeutic
inhibition of tissue factor. Specific and non-specific inhibitors of tissue
factor or the tissue factor/factor VIIa complex have been developed or
identified, and have been tested in experimental studies. Clinical studies are
currently being initiated. In this review, we present the current knowledge on
the role of tissue factor in atherosclerosis, arterial intervention and potential
pharmacological approaches, with focus on acute coronary syndromes. N. Ref:: 162
----------------------------------------------------
[55]
- 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
----------------------------------------------------
[56]
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
----------------------------------------------------
[57]
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
----------------------------------------------------
[58]
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
----------------------------------------------------
[59]
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
----------------------------------------------------
[60]
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
----------------------------------------------------
[61]
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
----------------------------------------------------
[62]
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.
----------------------------------------------------
[63]
TÍTULO / TITLE: - Measle virus-infected
dendritic cells develop immunosuppressive and cytotoxic activities.
REVISTA
/ JOURNAL: - Immunobiology 2001 Dec;204(5):629-38.
AUTORES
/ AUTHORS: - Vidalain PO; Azocar O; Rabourdin-Combe C;
Servet-Delprat C
INSTITUCIÓN
/ INSTITUTION: - Immunobiologie Fondamentale et Clinique, CERVI-INSERM,
Lyon, France. servet@cervi-lyon.inserm.fr
RESUMEN
/ SUMMARY: - Measle virus (MV) infection induces a
transient but profound immunosuppression characterized by a panlymphopenia
which occasionally results in opportunistic infections responsible for a high
rate of mortality in malnourished children. MV can encounter human dendritic
cells (DC) in the respiratory mucosa or in the secondary lymphoid organs. After
a brief presentation of DCs, we review progress in understanding the
immunobiology of MV-infected DCs that could account for MV-induced
immunosuppression. In addition, we develop the newly described TRAIL-mediated
cytotoxic function of DCs that is turned on by MV infection, but also by interferons
or double-stranded RNA (poly (I:C)). Finally, we propose a model where the
measles-associated lymphopenia could be mediated by TRAIL and the
measles-induced immunosuppression could be transiently prolonged by
Fas-mediated destruction of DCs. N.
Ref:: 38
----------------------------------------------------
[64]
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
----------------------------------------------------
[65]
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
----------------------------------------------------
[66]
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
----------------------------------------------------
[67]
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
----------------------------------------------------
[68]
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
----------------------------------------------------
[69]
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
----------------------------------------------------
[70]
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
----------------------------------------------------
[71]
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
----------------------------------------------------
[72]
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
----------------------------------------------------
[73]
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
----------------------------------------------------
[74]
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
----------------------------------------------------
[75]
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
----------------------------------------------------
[76]
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
----------------------------------------------------
[77]
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
----------------------------------------------------
[78]
- 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
----------------------------------------------------
[79]
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
----------------------------------------------------
[80]
TÍTULO / TITLE: - Neonatal toxic shock
syndrome-like exanthematous disease (NTED).
REVISTA
/ JOURNAL: - Pediatr Int 2003 Apr;45(2):233-7.
AUTORES
/ AUTHORS: - Takahashi N
INSTITUCIÓN
/ INSTITUTION: - Department of Pediatrics, Jichi Medical
School, Tochigi-ken, Tokyo Women’s Medical University, Tokyo, Japan. naoto-t@jichi.ac.jp
RESUMEN
/ SUMMARY: - The author and colleagues recently
discovered an emerging neonatal infectious disease: neonatal toxic shock
syndrome-like exanthematous disease (NTED), which is induced by the
superantigen toxic shock syndrome toxin-1 (TSST-1), produced by
methicillin-resistant Staphylococcus aureus (MRSA). The massively expanded
Vbeta2+ T cells were rapidly deleted in the peripheral blood of patients with
NTED. A marked depletion of Vbeta2+ T cells was also observed in the peripheral
blood before the expansion of these T cells. Anergy is specifically induced in
the TSST-1 reactive T cells of patients with NTED. Rapid recovery from NTED
without complications is expected to be related to the induction of immunologic
tolerance in neonatal patients. Anti-TSST-1 IgG antibody of maternal origin was
found to play a protective role in preventing the development of NTED. The
number of hospitals that have experience caring for patients with NTED has
increased threefold in the past 5 years. Most MRSA isolates from neonatal
intensive care units in Japan were found to be a single clone of coagulase type
II and to possess TSST-1 and staphylococcal enterotoxin C genes. The timing and
increased incidence of NTED suggest the emergence of a new MRSA clone. By
recognizing that TSST-1 can induce NTED, healthcare providers may give increased
attention to this disease in neonatal wards.
N. Ref:: 43
----------------------------------------------------
[81]
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
----------------------------------------------------
[82]
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
----------------------------------------------------
[83]
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
----------------------------------------------------
[84]
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
----------------------------------------------------
[85]
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
----------------------------------------------------
[86]
- 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
----------------------------------------------------
[87]
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
----------------------------------------------------
[88]
- 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
----------------------------------------------------
[89]
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.
----------------------------------------------------
[90]
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
----------------------------------------------------
[91]
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
----------------------------------------------------
[92]
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
----------------------------------------------------
[93]
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
----------------------------------------------------
[94]
TÍTULO / TITLE: - Pathophysiology of
traumatic brain edema: current concepts.
REVISTA
/ JOURNAL: - Acta Neurochir Suppl 2003;86:7-10.
AUTORES
/ AUTHORS: - Marmarou A
INSTITUCIÓN
/ INSTITUTION: - Division of Neurosurgery, Medical College
of Virginia, Virginia Commonwealth University, Richmond, VA 23298-0508, USA. marmarou@hsc.vcu.edu
RESUMEN
/ SUMMARY: - The generally held concept during the past
several decades is that traumatic brain edema is predominately vasogenic
emanating from the blood vessels subsequent to blood brain barrier compromise.
Much of the experimental data has focused on cryogenic injury models where
there clearly is a necrotic lesion surrounded by leaking vessels. However, in
closed head injury where brain swelling remains a critical problem, the
classification of the type of edema that develops is less clear. Most importantly,
studies in the clinical setting have ruled out vascular engorgement as one
potential mechanism and these studies have shown that edema and not blood
volume is the culprit responsible for brain swelling. We have put forth the
notion that traumatic brain edema is a combination of vasogenic and cellular
with the cellular component predominating. This article provides an update of
our current progress toward supporting this hypothesis and includes an update
on the role of aquaporins in traumatic brain edema. N. Ref:: 43
----------------------------------------------------
[95]
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
----------------------------------------------------
[96]
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
----------------------------------------------------
[97]
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
----------------------------------------------------
[98]
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
----------------------------------------------------
[99]
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
----------------------------------------------------
[100]
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.
----------------------------------------------------
[101]
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
----------------------------------------------------
[102]
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
----------------------------------------------------
[103]
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
----------------------------------------------------
[104]
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
----------------------------------------------------
[105]
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
----------------------------------------------------
[106]
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
----------------------------------------------------
[107]
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
----------------------------------------------------
[108]
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,
----------------------------------------------------
[109]
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.
----------------------------------------------------
[110]
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.
----------------------------------------------------
[111]
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
----------------------------------------------------
[112]
TÍTULO / TITLE: - Calcineurin and
hypertrophic heart disease: novel insights and remaining questions.
REVISTA
/ JOURNAL: - Cardiovasc Res 2002 Mar;53(4):806-21.
AUTORES
/ AUTHORS: - Bueno OF; van Rooij E; Molkentin JD;
Doevendans PA; De Windt LJ
INSTITUCIÓN
/ INSTITUTION: - Division of Molecular Cardiovascular
Biology, Department of Pediatrics, Children’s Hospital Medical Center,
Cincinnati OH, USA.
RESUMEN
/ SUMMARY: - In the past 2 years, an emerging body of
research has focused on a novel transcriptional pathway involved in the cardiac
hypertrophic response. Ever since its introduction, the significance of the
calcineurin-NFAT module has been subject of controversy. The aim of this review
is to provide both an update on the current status of knowledge and discuss the
remaining issues regarding the involvement of calcineurin in hypertrophic heart
disease. To this end, the molecular biology of calcineurin and its direct
downstream transcriptional effector NFAT are discussed in the context of the
genetic studies that established the existence of this signaling paradigm in
the heart. The pharmacological mode-of-action and specificity of the
calcineurin inhibitors cyclosporine A (CsA) and FK506 is discussed, as well as
their inherent limitations to study the biology of calcineurin. A critical
interpretation is given on studies aimed at analyzing the role of calcineurin
in cardiac hypertrophy using systemic immunosuppression. To eliminate the
controversy surrounding CsA/FK506 usage, recent studies employed genetic
inhibitory strategies for calcineurin, which confirm the pivotal role for this
signal transduction pathway in the ventricular hypertrophy response. Finally,
unresolved issues concerning the role of calcineurin in cardiac pathobiology
are discussed based upon the information available, including its controversial
role in cardiomyocyte viability, the reciprocal relationship between myocyte
Ca(2+) homeostasis and calcineurin activity and the relative importance of
calcineurin in relation to other hypertrophic signaling cascades. N. Ref:: 124
----------------------------------------------------
[113]
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
----------------------------------------------------
[114]
TÍTULO / TITLE: - Old and new tools to
dissect calcineurin’s role in pressure-overload cardiac hypertrophy.
REVISTA
/ JOURNAL: - Cardiovasc Res 2002 Feb 1;53(2):294-303.
AUTORES
/ AUTHORS: - Zhang W
INSTITUCIÓN
/ INSTITUTION: - Department of Internal
Medicine/Hypertension Division, The University of Texas Southwestern Medical
Center at Dallas, Dallas, TX 75390-8586, USA. wzhang@mednet.swmed.edu
RESUMEN
/ SUMMARY: - In the last several years, a number of
experiments have implicated a pivotal role of the
calcium/calmodulin-calcineurin dependent pathway as a final common signaling
mechanism by which diverse hypertrophic stimuli converge to mediate
hypertrophic responses in cardiomyocytes. Calcineurin inhibitors, i.e.
cyclosporine A (CsA) and FK506, can interrupt the pathway, thereby preventing
cardiac hypertrophy. The data that convincingly support this novel hypothesis
were derived either from in vitro studies in cultured cardiomyocytes or from in
vivo studies in transgenic mice. However, when the hypothesis was tested in
clinically relevant animal models of cardiac hypertrophy, controversial results
and conclusions emerged. In conventional models of cardiac hypertrophy, two
questions remain to be answered: (1) whether calcineurin is activated in
hypertrophied cardiac muscle, and (2) whether calcineurin inhibitors prevent
cardiac hypertrophy. In addition, clinical observations have revealed that
calcineurin inhibitors appear to exert pro-hypertrophic effects in organ
transplant recipients. The controversies suggest that current calcineurin inhibitors
are blunt tools for testing the hypothesis in pressure-overload hypertrophy in
vivo, because there are so many confounding effects that are associated with
systemic administration of the drugs. As such, new genetic approaches may
overcome some of the problems associated with pharmacological inhibitors. This
invited review will focus on the controversies surrounding the ability of
calcineurin inhibition to prevent conventional (pressure-overload) cardiac
hypertrophy and the new genetic approaches to address the question. N. Ref:: 93
----------------------------------------------------
[115]
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.
----------------------------------------------------
[116]
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
----------------------------------------------------
[117]
TÍTULO / TITLE: - The role of T
lymphocytes in the pathogenesis of asthma.
REVISTA
/ JOURNAL: - J Allergy Clin Immunol 2003
Mar;111(3):450-63; quiz 464.
AUTORES
/ AUTHORS: - Larche M; Robinson DS; Kay AB
INSTITUCIÓN
/ INSTITUTION: - Department of Allergy and Clinical
Immunology, Faculty of Medicine, Imperial College London, National Heart and
Lung Institute, London, United Kingdom.
RESUMEN
/ SUMMARY: - There is considerable evidence to support
a role for T cells in asthma, particularly the involvement of T(H)2 cells both
in atopic allergic asthma and in nonatopic and occupational asthma. There might
also be a minor contribution from T©2 CD8+ T cells. Several T(H)2 cytokines
have the potential to modulate airway inflammation, particularly IL-13, which
induces airway hyperresponsiveness independently of IgE and eosinophilia in
animal models. The identification of transcription factors controlling T(H)1
and T(H)2 development further support the T(H)2 hypothesis because GATA3 is
overexpressed and T-bet is underexpressed in the asthmatic airway. Specific T
cell directed immunotherapy might allow induction, modulation, or both of
T-cell responses, and elucidation of the mechanisms of regulatory T cells might
allow further optimization of immunotherapy. Recent advances in our
understanding of dendritic cell function in directing T-cell responses might
uncover further therapeutic targets. The efficacy of cyclosporin A and anti-CD4
treatment in patients with chronic severe asthma argues for continued T-cell
involvement, but whether remodeling contributes to pathology inaccessible to
anti-inflammatory treatment or T-cell immunotherapy will be an important future
question. N. Ref:: 145
----------------------------------------------------
[118]
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
----------------------------------------------------
[119]
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
----------------------------------------------------
[120]
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
----------------------------------------------------
[121]
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
----------------------------------------------------
[122]
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
----------------------------------------------------
[123]
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
----------------------------------------------------
[124]
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
----------------------------------------------------
[125]
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
----------------------------------------------------
[126]
TÍTULO / TITLE: - Lichen planopilaris:
report of 30 cases and review of the literature.
REVISTA
/ JOURNAL: - Int J Dermatol 2003 May;42(5):342-5.
AUTORES
/ AUTHORS: - Chieregato C; Zini A; Barba A; Magnanini
M; Rosina P
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology, Verona
University, Verona, Italy. carlochiergto@hotmail.com
RESUMEN
/ SUMMARY: - BACKGROUND: Lichen planopilaris (LPP)
affects primarily the scalp, resulting in scaling, atrophy, and alopecia with
scarring. The purpose of our study was to obtain original data on LPP and to
evaluate the efficacy of topical therapy in comparison with systemic therapies.
METHODS: We examined 30 patients affected by LPP between 1996 and 2001,
performing clinical, laboratory, histopathologic and direct immunofluorescence
examinations. Twenty-one of the patients (70%) were women and nine (30%) were men.
The average age at presentation was 51.5 years. The average duration of the
disease was 13 months at the time of the diagnosis. All patients received
topical steroids for a total of 12 weeks. RESULTS: Resolution of the
inflammatory process and blocking of the cicatricial progression were observed
in 66% of cases, a mild reduction of fibrosis and cicatrization in 20% of
patients, and no response in 13%. CONCLUSIONS: We concluded that topical
therapy may be a valid alternative to systemic therapies, especially in
patients with lesions in the early phase.
N. Ref:: 6
----------------------------------------------------
[127]
TÍTULO / TITLE: - Risk factors for
bronchiolitis obliterans: a systematic review of recent publications.
REVISTA
/ JOURNAL: - J Heart Lung Transplant 2002
Feb;21(2):271-81.
AUTORES
/ AUTHORS: - Sharples LD; McNeil K; Stewart S; Wallwork
J
INSTITUCIÓN
/ INSTITUTION: - Medical Research Council (MRC)
Biostatistics Unit, University Forvie Site, Papworth Everard, Cambridge, United
Kingdom. linda.sharples@mrc-bsu.cam.ac.uk
RESUMEN
/ SUMMARY: - BACKGROUND: Obliterative bronchiolitis
remains the major limitation to long-term survival after lung transplantation.
A thorough understanding of the factors that confer high risk of developing
obliterative bronchiolitis or its physiologic surrogate bronchiolitis
obliterans syndrome is important to help define therapeutic strategies.
METHODS: We performed a systematic review of studies published since the
beginning of 1990. The review excluded non-human studies, publications before
1990, small (less than 25 patients) studies that were predominantly concerned
with investigating the pathogenesis of obliterative bronchiolitis, studies
solely concerned with diagnosis or treatment of obliterative bronchiolitis, and
overlapping studies from the same center. Onset of bronchiolitis obliterans
syndrome or obliterative bronchiolitis was the outcome of interest. RESULTS:
Acute rejection plays an important role in obliterative bronchiolitis and
bronchiolitis obliterans syndrome onset, and late rejection is a significant
risk factor. Lymphocytic bronchitis/bronchiolitis is also a risk factor, with
some evidence that late onset is associated with greater risk. The effects of
cytomegalovirus, other infectious organisms, and human leukocyte antigen
matching are less clear and require further confirmation. There is little
evidence that recipient and donor characteristics play a major role.
CONCLUSIONS: This systematic review supports the view that obliterative
bronchiolitis arises from alloimmunologic injury marked by clinically apparent
acute rejection episodes and that inflammatory conditions, including viral
infections or ischemic injury, may also play a role. Implications for therapy
are discussed. N.
Ref:: 28
----------------------------------------------------
[128]
TÍTULO / TITLE: - Long-term care of
pediatric renal transplant patients: from bench to bedside.
REVISTA
/ JOURNAL: - Curr Opin Pediatr 2002 Apr;14(2):205-10.
AUTORES
/ AUTHORS: - Samsonov D; Briscoe DM
INSTITUCIÓN
/ INSTITUTION: - Division of Nephrology, Department of
Medicine, Children’s Hospital and Harvard Medical School, Boston, Massachusetts
02115, USA.
RESUMEN
/ SUMMARY: - In this review, we discuss current and
future issues in the management of pediatric renal transplant recipients,
including the optimization of long-term graft function and the minimization of
complications caused by immunosuppression. Long-term management involves not only
the monitoring of graft function but also the identification of patients at
risk for the development of complications. The identification of patients with
immunoreactive or immunoregulatory responses can be performed molecular
monitoring of the immune response. Also, the use of frequent surveillance
kidney biopsies, surrogate markers of chronic rejection, and glomerular
filtration rate will be a part of future management. Identifying high-risk
patients enables the physician to optimize immunosuppression to limit acute
rejection. Short-and long-term management of pediatric transplant patients also
includes adequate monitoring of growth and the monitoring for post-transplant
lymphoproliferative disease. Ongoing clinical trials are underway that focus on
these novel approaches in caring for pediatric transplant recipients. N. Ref:: 41
----------------------------------------------------
[129]
TÍTULO / TITLE: - Minimizing calcineurin
inhibitor drugs in renal transplantation.
REVISTA
/ JOURNAL: - Transplant Proc 2003 May;35(3
Suppl):118S-121S.
AUTORES
/ AUTHORS: - Flechner SM
INSTITUCIÓN
/ INSTITUTION: - Section of Renal Transplantation,
Transplant Center A110, Cleveland Clinic Foundation, Cleveland, Ohio 44195,
USA.
RESUMEN
/ SUMMARY: - Calcineurin inhibitor drugs (CNI),
primarily cyclosporine then tacrolimus, have been the centerpieces of
maintenance immunosuppression for kidney transplantation since their
introduction in the 1980s. While these drugs have been responsible for improved
short-term outcomes and diminished rates of acute rejection, they are
nephrotoxic and can cause permanent renal injury in many patients. Indeed, some
have found that at 10 years after transplantation, the benefits of CNI drugs
have been lost compared to the previous generation of maintenance
immunosuppression. The use of these agents over many years contributes to the
antigen-independent decline in renal function referred to as chronic allograft
nephropathy. However, it remains unclear to what degree the use of CNI drugs contribute
to ultimate graft loss. For these reasons immunosuppressive alternatives to CNI
drugs have begun to emerge during the past few years. The recent introduction
of the potent immunosuppressive agent sirolimus has afforded an opportunity to
develop a regimen designed to maximize prophylaxis of early acute rejection,
absent drug-induced nephrotoxicity. It was our feeling that the combination of
antibody induction therapy combined with sirolimus substitution in a three-drug
maintenance regimen, would provide the best posttransplant renal function and
lowest rates of acute rejection. We have developed a CNI-free immunosuppressive
regimen consisting of basiliximab induction, followed by sirolimus, MMF and
steroids. Using this protocol we demonstrated comparable transplant outcomes
with improved renal function in adult recipients of primary renal transplants.
Limiting nephrotoxic immunosuppression should be considered an important goal;
but requires sufficient long-term follow-up to support the benefits suggested
from initial analysis of the data. N.
Ref:: 23
----------------------------------------------------
[130]
TÍTULO / TITLE: - Chronic
graft-versus-host disease manifesting as polymyositis: an uncommon
presentation.
REVISTA
/ JOURNAL: - Bone Marrow Transplant 2002
Oct;30(8):543-6.
●●
Enlace al texto completo (gratuito o de pago) 1038/sj.bmt.1703711
AUTORES
/ AUTHORS: - Couriel DR; Beguelin GZ; Giralt S; De Lima
M; Hosing C; Kharfan-Dabaja MA; Anagnostopoulos A; Champlin R
INSTITUCIÓN
/ INSTITUTION: - Department of Blood and Marrow
Transplantation, University of Texas, MD Anderson Cancer Center, Houston, TX
77030, USA.
RESUMEN
/ SUMMARY: - Graft-versus-host disease (GVHD) remains a
major complication of allogeneic hematopoietic stem cell transplantation.
Polymyositis can occur in association with chronic GVHD and mimics the
idiopathic form of the disease. We report two cases of chronic GVHD-associated
polymyositis and review the published literature. The two patients presented 13
and 19 months after allogeneic transplantation with characteristic features of
muscular hypotrophy, proximal muscle weakness, pain, elevated creatine
phosphokinase (CPK), aldolase and SGPT. Interestingly, both patients had HLA
DR52 genes, which is frequently reported in association with idiopathic
polymyositis. Electromyogram (EMG) and muscle biopsy confirmed the diagnosis.
Treatment with cyclosporine or tacrolimus resulted in complete and sustained
remission of polymyositis in both cases. A review of the literature shows
cyclosporine and steroids are well-described treatment options for patients
with myositis in post transplant, as well as idiopathic cases. The duration of
immunosuppressive treatment has varied in different reports, and there is a
risk of recurrence when immunosuppression is tapered. N. Ref:: 32
----------------------------------------------------
[131]
TÍTULO / TITLE: - FTY720: targeting
G-protein-coupled receptors for sphingosine 1-phosphate in transplantation and
autoimmunity.
REVISTA
/ JOURNAL: - Curr Opin Immunol 2002 Oct;14(5):569-75.
AUTORES
/ AUTHORS: - Brinkmann V; Lynch KR
INSTITUCIÓN
/ INSTITUTION: - Novartis Pharma AG Transplantation
Research WSJ-386.101, CH-4002 Basel, Switzerland. volker.brinkmann@pharma.novartis.com
RESUMEN
/ SUMMARY: - The novel immunomodulator FTY720 is
remarkably effective in models of transplantation and autoimmunity. Recent data
show that phosphorylated FTY720 is an agonist at four sphingosine 1-phosphate
receptors. Stimulation of sphingosine 1-phosphate receptors leads to
sequestration of lymphocytes in secondary lymphatic tissues and thus away from
inflammatory lesions and graft sites. N.
Ref:: 44
----------------------------------------------------
[132]
TÍTULO / TITLE: - Exploring treatment
options in renal transplantation: the problems of chronic allograft dysfunction
and drug-related nephrotoxicity.
REVISTA
/ JOURNAL: - Transplantation 2001 Jun 15;71(11
Suppl):SS42-51.
AUTORES
/ AUTHORS: - Campistol JM; Grinyo JM
INSTITUCIÓN
/ INSTITUTION: - University of Barcelona, España.
RESUMEN
/ SUMMARY: - The immunosuppressive benefits of
cyclosporine and tacrolimus in short-term and medium-term renal allograft
survival are well documented. It is becoming increasingly clear that the basis
of this immunosuppression, the inhibition of calcineurin, may be linked with
nephrotoxicity, hypertension, hyperlipidemia, and new-onset diabetes mellitus,
side effects that may lead to CRAD, death due to CVD, and late renal allograft
loss. This clinical picture presents a clear need for new strategies that
produce adequate immunosuppression to prevent acute rejection while
simultaneously reducing the side effects associated with CNI-related therapies.
Sirolimus combined with cyclosporine and tacrolimus has demonstrated an ability
to reduce incidences of early acute rejection and, used as base therapy, has
provided protection against acute rejection equivalent to that of cyclosporine,
without the consequent nephrotoxicity associated with CNIs. In preliminary
results from an ongoing clinical trial, sirolimus has been used to eliminate
cyclosporine during maintenance immunosuppression, with subsequent improvements
in measures of blood pressure and renal function. In addition, the
antiproliferative properties of sirolimus and its ability to prevent graft
vascular disease in animal studies make sirolimus a promising agent to decrease
incidences of CRAD and improve long-term renal allograft survival. These
findings point to a clear need to further explore both the efficacy of
sirolimus immunotherapy and its long-term effects. N. Ref:: 126
----------------------------------------------------
[133]
TÍTULO / TITLE: - Histopathological study
of intrahepatic islets transplanted in the nonhuman primate model using
edmonton protocol immunosuppression.
REVISTA
/ JOURNAL: - J Clin Endocrinol Metab. Acceso gratuito
al texto completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://jcem.endojournals.org/
●●
Cita: J. of Clin Endocrinol & Metab: <> 2002 Dec;87(12):5424-9.
AUTORES
/ AUTHORS: - Hirshberg B; Mog S; Patterson N; Leconte
J; Harlan DM
INSTITUCIÓN
/ INSTITUTION: - Transplantation and Autoimmunity Branch,
National Institute of Diabetes and Digestive and Kidney Diseases, National
Institutes of Health, Bethesda, Maryland 20892, USA.
RESUMEN
/ SUMMARY: - While islet cell transplantation is a
promising way to restore insulin independence to patients with type I diabetes
mellitus, a detailed histological analysis of the transplanted, intraportal
islets has not yet been reported. Rhesus macaques underwent total
pancreatectomy, then had allogeneic isolated islets infused into their portal
vein, followed by daclizumab, tacrolimus, and sirolimus to prevent islet
rejection. Islets were evenly distributed among the liver lobes. Liver sections
from a primate given allogeneic islets 5 d earlier did not display any islet
capillary formation, whereas intrahepatic islets transplanted 30 and 90 d
before euthanasia showed an abundant capillary supply. Localized hepatocellular
glycogenosis was observed surrounding the islets in a primate with functioning
islets 7 months post transplant. Liver sections from a primate that rejected
islets transplanted 2 months prior displayed only islet remnants with prominent
local lymphohistiocytic inflammation and an occasional capillary. We conclude
that islets develop an abundant vascular supply within 30 d following
transplant and because capillaries persist even following rejection, that the
vascular cells are likely from the recipient. While transplanted islets were
not vascularized early post transplant, the primates remained insulin
independent. The long-term consequence of islets in the liver, marked by the
glycogenosis, remains unknown and warrants further study.
----------------------------------------------------
[134]
TÍTULO / TITLE: - Resolution of oral non-Hodgkin’s
lymphoma by reduction of immunosuppressive therapy in a renal allograft
recipient: a case report and review of the literature.
REVISTA
/ JOURNAL: - Oral Surg Oral Med Oral Pathol Oral Radiol
Endod 2002 Dec;94(6):697-701.
●●
Enlace al texto completo (gratuito o de pago) 1067/moe.2002.126889
AUTORES
/ AUTHORS: - Keogh PV; Fisher V; Flint SR
INSTITUCIÓN
/ INSTITUTION: - Department of Oral Surgery, Oral Medicine
and Oral Pathology, Dublin Dental School and Hospital, Trinity College,
Ireland. pakeogh@dental.tcd.ie
RESUMEN
/ SUMMARY: - A case of oral non-Hodgkin’s lymphoma
arising in a patient with insulin-dependent diabetes who had undergone renal
allograft transplantation is described. The resolution of the disease was
achieved by a reduction in her immunosuppressive therapy. The differential
diagnosis is discussed, and the management of posttransplantation lymphoproliferative
disorders is reviewed. N.
Ref:: 40
----------------------------------------------------
[135]
TÍTULO / TITLE: - The mucosa of the small
intestine: how clinically relevant as an organ of drug metabolism?
REVISTA
/ JOURNAL: - Clin Pharmacokinet 2002;41(4):235-53.
AUTORES
/ AUTHORS: - Doherty MM; Charman WN
INSTITUCIÓN
/ INSTITUTION: - Department of Pharmaceutics, Victorian
College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Victoria
3052, Australia. margaret.doherty@vcp.monash.edu.au
RESUMEN
/ SUMMARY: - The intestinal mucosa is capable of
metabolising drugs via phase I and II reactions. Increasingly, as a result of
in vitro and in vivo (animal and human) data, the intestinal mucosa is being
implicated as a major metabolic organ for some drugs. This has been supported
by clinical studies of orally administered drugs (well-known examples include
cyclosporin, midazolam, nifedipine and tacrolimus) where intestinal drug metabolism
has significantly reduced oral bioavailability. This review discusses the
intestinal properties and processes that contribute to drug metabolism. An
understanding of the interplay between the processes controlling absorption,
metabolism and P-glycoprotein-mediated efflux from the intestinal mucosa into
the intestinal lumen facilitates determination of the extent of the intestinal
contribution to first-pass metabolism. The clinical relevance of intestinal
metabolism, however, depends on the relative importance of the metabolic
pathway involved, the therapeutic index of the drug and the inherent inter- and
intra-individual variability. This variability can stem from genetic
(metabolising enzyme polymorphisms) and/or non-genetic (including concomitant
drug and food intake, route of administration) sources. An overwhelming
proportion of clinically relevant drug interactions where the intestine has
been implicated as a major contributor to first-pass metabolism involve drugs
that undergo cytochrome P450 (CYP) 3A4-mediated biotransformation and are
substrates for the efflux transporter P-glycoprotein. Much work is yet to be
done in characterising the clinical impact of other enzyme systems on drug
therapy. In order to achieve this, the first-pass contributions of the
intestine and liver must be successfully decoupled. N. Ref:: 130
----------------------------------------------------
[136]
TÍTULO / TITLE: - Transplantation:
toxicokinetics and mechanisms of toxicity of cyclosporine and macrolides.
REVISTA
/ JOURNAL: - Curr Opin Investig Drugs 2003
Nov;4(11):1287-96.
AUTORES
/ AUTHORS: - Serkova N; Christians U
INSTITUCIÓN
/ INSTITUTION: - Department of Anesthesiology, Clinical
Research & Development, University of Colorado Health Sciences Center, 4200
East Ninth Ave, Room UH-2122, Campus Box B113, Denver, CO 80262, USA.
RESUMEN
/ SUMMARY: - For over two decades, calcineurin
inhibitors (CIs) have been the mainstay of immunosuppressive therapy following
solid-organ transplantation. However, CI nephrotoxicity is one of the main
contributors to chronic kidney allograft dysfunction. A novel class of
immunosuppressants that inhibit the kinase mammalian target of rapamycin
(mTOR), although not nephrotoxic themselves, enhance CI nephrotoxicity. The
biochemical basis of CI toxicity and their toxicodynamic interaction with mTOR
inhibitors is still poorly understood. Studies using a magnetic resonance
spectroscopy-based metabonomic approach indicate that CI toxicity is caused by
drug-induced mitochondrial dysfunction and that mTOR inhibitors enhance the
negative effects of CIs on cell energy metabolism. N. Ref:: 77
----------------------------------------------------
[137]
TÍTULO / TITLE: - Risk factors for and
management of post-transplantation cardiovascular disease.
REVISTA
/ JOURNAL: - BioDrugs 2001;15(4):261-78.
AUTORES
/ AUTHORS: - Fellstrom B
INSTITUCIÓN
/ INSTITUTION: - Department of Medical Sciences, University
Hospital, SE-751 85 Uppsala, Sweden. bengt.fellstrom@medsci.uu.se
RESUMEN
/ SUMMARY: - The mortality rates due to cardiovascular
disease (CVD) in transplant recipients are greater than in the general
population. CVD is a major cause of both graft loss and patient death in renal
transplant recipients, and improving cardiovascular health in transplant
recipients will presumably help to extend both patient and graft survival.
Further studies are needed to better evaluate the effectiveness of risk
modification on subsequent CVD morbidity and mortality. There is no reason to
consider risk factors for CVD such as hyperlipidaemia, hypertension and
diabetes mellitus in transplant recipients differently from in the general
population. In addition, there are specific transplantation risk factors such
as acute rejection episodes and the use of immunosuppressive drugs. It is
obvious that several of the immunosuppressive agents used today have
disadvantageous influences on risk factors for CVD such as hyperlipidaemia,
hypertension and post-transplantation diabetes mellitus (PTDM), but the
relative importance of immunosuppressant-induced increases in these risk
factors is basically unknown. This may be a strong argument for the selective
use and individual tailoring of immunosuppressive agents based upon the risk
factor profile of the patient, without jeopardising the function of the graft.
Hyperlipidaemia is common after transplantation, and immunosuppression with
corticosteroids, cyclosporin, or sirolimus (rapamycin) causes different types
of post-transplantation hyperlipidaemia. However, to date, no studies have
demonstrated that lipid lowering strategies significantly reduce CVD morbidity
or mortality and improve allograft survival in transplant recipients. Several
studies using preventive or interventional approaches are ongoing and will be
reported in the near future. Post-transplantation hypertension appears to be a
major risk factor determining graft and patient survival, and immunosuppressive
agents have different effects on hypertension. Controlled studies support the
opinion that post-transplantation hypertension must be treated as strictly as
in a population with essential hypertension, diabetes mellitus, or chronic
renal failure. As increasing numbers of immunosuppressive agents become
available for use, we may be in a better position to tailor immunosuppressive
therapy to the individual patient, avoiding the use of diabetogenic drugs, drug
combinations, or inappropriate doses in patients susceptible to PTDM. Multiple
acute rejection episodes have also been demonstrated to be a risk factor for
CVD - a strong argument for the use of immunosuppressive drugs to reduce acute
rejection. Until we have a better understanding from ongoing landmark studies
on the management of CVD, presently available therapy to reduce risk factors
needs to be used together with individual tailoring of immunosuppressive
therapy with the aim of reducing CVD in these patients. N. Ref:: 138
----------------------------------------------------
[138]
TÍTULO / TITLE: - The cytology of HIV-induced
immunosuppression. Changing pattern of disease in the era of highly active
antiretroviral therapy.
REVISTA
/ JOURNAL: - Cytopathology 2001 Oct;12(5):281-96.
AUTORES
/ AUTHORS: - Kocjan G; Miller R
INSTITUCIÓN
/ INSTITUTION: - Department of Histopathology, Royal Free
and University College Medical School, University College London, UK. N. Ref:: 89
----------------------------------------------------
[139]
TÍTULO / TITLE: - The effect of
immunosuppressive protocols on spontaneous CNS remyelination following
toxin-induced demyelination.
REVISTA
/ JOURNAL: - J Neuroimmunol 2001 Oct 1;119(2):261-8.
AUTORES
/ AUTHORS: - Smith PM; Franklin RJ
INSTITUCIÓN
/ INSTITUTION: - Department of Clinical Veterinary
Medicine, University of Cambridge, Madingley Road, CB3 0ES, Cambridge, UK.
RESUMEN
/ SUMMARY: - Glial cell transplantation is a potential
therapy for human demyelinating disease, though obtaining large numbers of
human myelinating cells for transplantation remains a major stumbling block.
Autologous transplantation is currently not possible, since the adult human CNS
is not a good source of oligodendrocyte precursors, and long-term
immunosuppression of engrafted allogeneic or xenogeneic cells is therefore
likely to be necessary. Immunosuppressive drugs may need to be used in
situations where more recent, active areas of demyelination are undergoing
endogenous remyelination. It is therefore pertinent to establish the extent to
which immunosuppressive protocols will suppress spontaneous remyelination. In
order to investigate this issue, we created demyelinating lesions in the spinal
cord of adult rats and compared the extent of remyelination in animals
receiving different immunosuppressive treatments. In animals given only
cyclosporin A, there was no difference in the extent of either Schwann cell or
oligodendrocyte remyelination of ethidium bromide-induced demyelinating
lesions. However, in animals given cyclophosphamide, either alone or in
combination with cyclosporin, there was a significant reduction in the extent
of oligodendrocyte-mediated remyelination. These results demonstrate that
cyclophosphamide is deleterious to oligodendrocyte remyelination and for this
reason should be used with caution in patients with demyelinating disease.
----------------------------------------------------
[140]
TÍTULO / TITLE: - Non-steroidal topical
immunomodulators provide skin-selective, self-limiting treatment in atopic
dermatitis.
REVISTA
/ JOURNAL: - Eur J Dermatol 2003 Sep-Oct;13(5):455-61.
AUTORES
/ AUTHORS: - Bos JD
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology A0-235, Academic
Medical Centre, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The
Netherlands. j.d.bos@amc.uva.nl
RESUMEN
/ SUMMARY: - Topical corticosteroids are the mainstay
of treatment for atopic dermatitis; however, their clinical utility is limited
by potential side effects. Recently, the steroid-free topical immunomodulators
tacrolimus ointment and pimecrolimus cream have become available. These agents
provide effective treatment without causing skin atrophy or other steroidal
side effects, and their physiochemical properties, such as relatively large
molecular size and high lipophilicity, limit diffusion through skin and into the
bloodstream, providing skin-selective treatment. Clinical trials with more than
1,700 paediatric and adult patients have demonstrated that treatment with
either agent is associated with minimal systemic absorption of tacrolimus or
pimecrolimus. Additionally, studies have shown that percutaneous absorption of
tacrolimus decreases as treatment continues and clinical improvement occurs.
This self-limiting facet of the treatment, together with the skin-selectivity
of topical immunomodulators, is reflected in the good safety and tolerability
profiles of these agents, which promise to significantly improve the long-term
management of atopic dermatitis. N.
Ref:: 56
----------------------------------------------------
[141]
TÍTULO / TITLE: - Bilateral keratoconjunctivitis
associated with lichen planus.
REVISTA
/ JOURNAL: - Cornea 2004 Jan;23(1):100-5.
AUTORES
/ AUTHORS: - Rhee MK; Mootha VV
INSTITUCIÓN
/ INSTITUTION: - Eye and Ear Institute of Pittsburgh,
University of Pittsburgh, Pittsburgh, PA, USA.
RESUMEN
/ SUMMARY: - PURPOSE: To describe a case of bilateral
keratoconjunctivitis in a patient with lichen planus. METHODS: Case report and
review of the English literature. RESULTS: To our knowledge, this is the fourth
reported case of keratoconjunctivitis associated with lichen planus. A
33-year-old Navajo man with lichen planus had recurrent and progressive
keratoconjunctivitis that failed to improve on multiple topical medications.
Tapered oral prednisone, 2% topical cyclosporin, and amniotic membrane transplantation
pacified the acute exacerbation. CONCLUSIONS: Our patient with lichen planus
developed an ocular surface disease with cicatricial conjunctivitis,
keratouveitis, keratoconjunctivitis sicca, punctate epithelial erosions, and
persistent epithelial defects leading to noninfectious or infectious corneal
ulceration. Amniotic membrane transplantation may play an adjunctive role in
refractory cases of lichen planus-related keratoconjunctivitis. Topical
cyclosporin may stabilize the ocular surface when combined with systemic
immunosuppression in severe cases. N.
Ref:: 20
----------------------------------------------------
[142]
TÍTULO / TITLE: - Therapeutic drug
monitoring of immunosuppressant drugs in clinical practice.
REVISTA
/ JOURNAL: - Clin Ther 2002 Mar;24(3):330-50;
discussion 329.
AUTORES
/ AUTHORS: - Kahan BD; Keown P; Levy GA; Johnston A
INSTITUCIÓN
/ INSTITUTION: - Division of Immunology and Organ
Transplantation, University of Texas Health Science Center at Houston Medical
School, 77030, USA. Barry.D.Kahan@uth.tmc.edu
RESUMEN
/ SUMMARY: - BACKGROUND: Therapeutic drug monitoring
(TDM) is essential to maintain the efficacy of many immunosuppressant drugs
while minimizing their toxicity. TDM has become more refined with the
development of new monitoring techniques and more specific assays. OBJECTIVE:
This article summarizes current data on TDM of the following immunosuppressant
drugs used in organ transplantation: cyclosporine, tacrolimus, sirolimus,
everolimus, and mycophenolate mofetil. METHODS: Published data were identified
by a MEDLINE search of the English-language literature through March 2001 using
the terms therapeutic drug monitoring, cyclosporine, tacrolimus, sirolimus,
everolimus, and mycophenolate mofetil. Relevant conference abstracts were also
included. RESULTS: TDM of cyclosporine has been well studied, and recent
findings indicate that monitoring of drug levels 2 hours after dosing is a more
sensitive predictor of outcome than trough (C0) monitoring. C0 levels are being
used more widely in TDM of tacrolimus; however, the relationship between C0 and
area under the curve has varied widely in clinical trials, with correlations
ranging from 0.11 to 0.92. The use of TDM of sirolimus, everolimus, and
mycophenolate mofetil is evolving rapidly. CONCLUSIONS: TDM of
immunosuppressant drugs that have a narrow therapeutic index is an increasingly
useful tool for minimizing drug toxicity while maximizing prevention of graft
loss and organ rejection. N.
Ref:: 85
----------------------------------------------------
[143]
TÍTULO / TITLE: - Immunosuppressive and
cytotoxic drugs in the treatment of rheumatic skin disorders.
REVISTA
/ JOURNAL: - Semin Cutan Med Surg 2001 Mar;20(1):58-68.
AUTORES
/ AUTHORS: - Callen JP
INSTITUCIÓN
/ INSTITUTION: - Division of Dermatology, University of
Louisville School of Medicine, KY 40202, USA. jefca@aol.com
RESUMEN
/ SUMMARY: - Cytotoxic and immunosuppressive drugs are
regularly used to treat proliferative, immunologically mediated inflammatory
disorders and some neoplastic diseases of the skin. Methotrexate, azathioprine,
mycophenolate mofetil, cyclosporin cyclophosphamide, chlorambucil, and other
related drugs have potential benefits in the treatment of severe and/or
recalcitrant rheumatic skin diseases. The therapeutic window for these agents
is narrow. The major uses of these drugs are for life-threatening cutaneous
disorders or as steroid-sparing agents.
N. Ref:: 57
----------------------------------------------------
[144]
TÍTULO / TITLE: - Drug-eluting stents in
peripheral vascular disease: eliminating restenosis.
REVISTA
/ JOURNAL: - Mt Sinai J Med. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.mssm.edu/msjournal/
●●
Cita: Mount Sinai J. of Medicine, New York: <> 2003 Nov;70(6):417-9.
AUTORES
/ AUTHORS: - Ellozy SH; Carroccio A
INSTITUCIÓN
/ INSTITUTION: - Department of Surgery, Mount Sinai School
of Medicine, One East 100th Street, New York, NY 10029, USA. sharif.ellozy@msnyuhealth.org
RESUMEN
/ SUMMARY: - Transcatheter endovascular therapy for
peripheral atherosclerotic disease has become more popular. In general, good
results have been reported in focal aortoiliac disease. However, the long-term
patency of angioplasty in longer, more distal lesions has been less
satisfactory. Stenting has not been shown to improve long-term patency compared
to angioplasty alone. Drug-eluting stents have shown promise in preventing
coronary restenosis, and preliminary results in peripheral arterial disease are
encouraging. This review article will discuss the current status of
endovascular therapy of aortoiliac and femoropopliteal atherosclerotic disease,
the theoretic and experimental basis for the use of drug-eluting stents, and
the preliminary results in human studies.
N. Ref:: 48
----------------------------------------------------
[145]
TÍTULO / TITLE: - Cyclosporine in the
treatment of idiopathic focal segmental glomerulosclerosis.
REVISTA
/ JOURNAL: - Semin Nephrol 2003 Mar;23(2):234-41.
●●
Enlace al texto completo (gratuito o de pago) 1053/snep.2003.50022
AUTORES
/ AUTHORS: - Cattran DC
INSTITUCIÓN
/ INSTITUTION: - Department of Medicine, Toronto General
Hospital, University Health Network, Toronto, Ontario, Canada. daniel.cattran@uhn.on.ca
RESUMEN
/ SUMMARY: - Cyclosporine a known powerful
immunosuppressive medication and has been used in the treatment of focal
segmental glomerulosclerosis (FSGS) for over a decade. Its precise mechanism of
action in this disorder is still debated and is likely at more than one level
related to the pathophysiology of the disease. Multiple studies have been
performed but the numbers of randomized trials of this drug in this disease are
very limited. However, both the best studies in children and adults indicate in
the steroid-resistant patients that 50% to 70% will have a response in terms of
a significant reduction in proteinuria. Provided the total dose is kept to 5
mg/kg or less and duration to less than 12 months, the drug is safe but careful
monitoring is required to maintain the blood pressure at ideal levels and to
avoid nephrotoxicity. Relapses are common, but rather than considering this a
failure of therapy the drug should be reintroduced because in most cases it
will reestablish control of the proteinuria. Although in the past cyclosporine
has been considered a second-line agent in FSGS, emerging data would suggest in
the high-risk patients related to corticosteroid toxicity it should be
considered primary therapy. N.
Ref:: 37
----------------------------------------------------
[146]
TÍTULO / TITLE: - The potential of
chitosan in ocular drug delivery.
REVISTA
/ JOURNAL: - J Pharm Pharmacol 2003 Nov;55(11):1451-63.
●●
Enlace al texto completo (gratuito o de pago) 1211/0022357022476
AUTORES
/ AUTHORS: - Alonso MJ; Sanchez A
INSTITUCIÓN
/ INSTITUTION: - Department of Pharmacy and Pharmaceutical
Technology, Faculty of Pharmacy, University of Santiago de Compostela, 15782
Santiago de Compostela, España. ffmjalon@usc.es
RESUMEN
/ SUMMARY: - This paper presents an overview of the
potential of chitosan-based systems for improving the retention and
biodistribution of drugs applied topically onto the eye. Besides its low
toxicity and good ocular tolerance, chitosan exhibits favourable biological
behaviour, such as bioadhesion- and permeability-enhancing properties, and also
interesting physico-chemical characteristics, which make it a unique material
for the design of ocular drug delivery vehicles. The review summarizes the
techniques for the production of chitosan gels, chitosan-coated colloidal
systems and chitosan nanoparticles, and describes their mechanism of action
upon contact with the ocular mucosa. The results reported until now have
provided evidence of the potential of chitosan gels for enhancing and
prolonging the retention of drugs on the eye surface. On the other hand,
chitosan-based colloidal systems were found to work as transmucosal drug
carriers, either facilitating the transport of drugs to the inner eye
(chitosan-coated colloidal systems containing indometacin) or their
accumulation into the corneal/conjunctival epithelia (chitosan nanoparticles containing
ciclosporin). Finally, the tolerance, toxicity and biodegradation of the
carriers under evaluation were reviewed.
N. Ref:: 75
----------------------------------------------------
[147]
TÍTULO / TITLE: - Rejection rate in
living donor kidney transplantation with and without basiliximab in
tacrolimus/mycophenolate mofetil-based protocol.
REVISTA
/ JOURNAL: - Transplant Proc 2003 Mar;35(2):653-4.
AUTORES
/ AUTHORS: - Rahamimov R; Yussim A; After T; Lustig S;
Bar-Nathan N; Shaharabani E; Shapira Z; Shabthai E; Mor E
INSTITUCIÓN
/ INSTITUTION: - Department of Transplantation, Rabin
Medical Center, Beilinson Campus, Petah-Tiqwa, Israel. rutir@clalit.org.il
----------------------------------------------------
[148]
TÍTULO / TITLE: - B19 virus infection in
renal transplant recipients.
REVISTA
/ JOURNAL: - J Clin Virol. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.elsevier.com/gej-ng/29/46/32/show/Products/VIRUSINT/index.htt
●●
Cita: J Clinical Virology: <> 2003 Apr;26(3):361-8.
AUTORES
/ AUTHORS: - Cavallo R; Merlino C; Re D; Bollero C;
Bergallo M; Lembo D; Musso T; Leonardi G; Segoloni GP; Ponzi AN
INSTITUCIÓN
/ INSTITUTION: - Virology Unit, Department of Public Health
and Microbiology, University of Turin, Via Santena 9, 10126, Turin, Italy. rossana.cavallo@unito.it
RESUMEN
/ SUMMARY: - BACKGROUND: B19 virus infection with
persistent anaemia has been reported in organ transplant recipients. Detection
of B19 virus DNA in serum is the best direct marker of active infection.
OBJECTIVE: The present study evaluated the incidence and clinical role of
active B19 virus infection in renal transplant recipients presenting with
anaemia. STUDY DESIGN: Forty-eight such recipients were investigated by nested
PCR on serum samples. The controls were 21 recipients without anaemia. Active
HCMV infection was also investigated as a marker of high immunosuppression.
RESULTS AND CONCLUSIONS: In 11/48 (23%) patients B19 virus DNA was demonstrated
in serum versus only 1/21 (5%) of the controls. Ten of these 11 patients had
already been seropositive at transplantation and active infection occurred in
eight of them during the first 3 months after transplantation. The remaining
patient experienced a primary infection 9 months after transplantation. Eight
(73%) of these 11 patients displayed a concomitant HCMV infection and four
(36%) showed increasing serum creatinine levels but none developed
glomerulopathy; 3/11 (27%) recovered spontaneously from anaemia whereas 8/11
(73%) needed therapy. In conclusion, the relatively high occurrence (23%) of
B19 virus infection in patients presenting with anaemia, suggests that it
should be considered in the differential diagnosis of persistent anaemia in
renal transplant recipients. Presence of the viral DNA should be assessed early
from transplantation and the viral load should be monitored to follow
persistent infection and better understand the relation between active
infection and occurrence of anaemia, and to assess the efficacy of IVIG therapy
and/or immunosuppression reduction in clearing the virus. N. Ref:: 56
----------------------------------------------------
[149]
- Castellano -
TÍTULO / TITLE:Nuevos tratamientos
inmunodepresores de induccion en el trasplante renal. New induction
immunosuppression treatments in kidney transplantation.
REVISTA
/ JOURNAL: - Med Clin (Barc). Acceso gratuito al texto
completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://db.doyma.es/
●●
Cita: Medicina Clínica: <> 2001 Jun 30;117(4):147-57.
AUTORES
/ AUTHORS: - Pascual J; Ortuno J
INSTITUCIÓN
/ INSTITUTION: - Servicio de Nefrologia. Universidad de
Alcala. Hospital Ramon y Cajal. Madrid. jpascual@hrc.insalud.es N. Ref:: 94
----------------------------------------------------
[150]
TÍTULO / TITLE: - Therapeutic monitoring
of mycophenolate mofetil in organ transplant recipients: is it necessary?
REVISTA
/ JOURNAL: - Clin Pharmacokinet 2002;41(5):319-27.
AUTORES
/ AUTHORS: - Mourad M; Wallemacq P; Konig J; de Frahan
EH; Eddour DC; De Meyer M; Malaise J; Squifflet JP
INSTITUCIÓN
/ INSTITUTION: - Department of Kidney and Pancreas
Transplantation, University Hospital Saint Luc, Universite Catholique de
Louvain, Brussels, Belgium. Michel.Mourad@chir.ucl.ac.be
RESUMEN
/ SUMMARY: - Adequate immunosuppression minimising the
risk of organ rejection with acceptable tolerability of the used drugs is a
crucial step in organ transplantation. The primary goal is to maintain a
consistent time-dependent target concentration by tailoring individual dosage leading
to the best efficacy and tolerability combination. The use of therapeutic drug
monitoring (TDM) to optimise immunosuppressive therapy is routinely employed
for maintenance drugs such as cyclosporin and tacrolimus. The question whether
therapeutic monitoring of mycophenolic acid (MPA) in organ transplant
recipients treated with mycophenolate mofetil is necessary is not definitely
answered. The correlation of mycophenolic acid pharmacokinetic parameters with
efficacy and toxicity makes the therapeutic monitoring of this drug promising.
However, further studies are mandatory to draw the best guidelines in order to
achieve higher levels of evidence that MPA-TDM may improve patient
outcome. N. Ref:: 63
----------------------------------------------------
[151]
TÍTULO / TITLE: - Osteoporosis after
solid organ and bone marrow transplantation.
REVISTA
/ JOURNAL: - Osteoporos Int 2003 Aug;14(8):617-30. Epub
2003 Aug 8.
●●
Enlace al texto completo (gratuito o de pago) 1007/s00198-003-1426-z
AUTORES
/ AUTHORS: - Cohen A; Shane E
INSTITUCIÓN
/ INSTITUTION: - College of Physicians & Surgeons of
Columbia University, 630 West 168th Street, New York, NY 10032, USA.
RESUMEN
/ SUMMARY: - Organ transplantation has become
increasingly common as a therapy for end-stage renal, liver, cardiac and
pulmonary disease. The population of patients who have survived organ transplantation
has grown dramatically over the last 2 decades. Although organ transplant
recipients now benefit from greatly improved survival, long-term complications
of organ transplantation, such as osteoporosis, adversely affect quality of
life and must be addressed. In the early post-transplantation period, the
effects of high dose glucocorticoids, combined with other immunosuppressive
drugs such as cycosporine A and tacrolimus, cause rapid bone loss particularly
at the spine and proximal femur. In this setting, fracture incidence rates as
high as 25-65% have been reported. Treatment and prevention strategies must
target this early post-transplant period, as well as the patient awaiting
transplantation and the long-term transplant recipient. This review will
discuss the clinical features of transplantation osteoporosis, the
pathophysiology of post-transplantation bone loss and prevention and therapy of
this unique bone disease. N.
Ref:: 182
----------------------------------------------------
[152]
TÍTULO / TITLE: - The Rapamune era of
immunosuppression 2003: the journey from the laboratory to clinical
transplantation.
REVISTA
/ JOURNAL: - Transplant Proc 2003 May;35(3
Suppl):18S-24S.
AUTORES
/ AUTHORS: - Camardo J
INSTITUCIÓN
/ INSTITUTION: - Wyeth Research, Collegeville, Pennsylvania
19426, USA.
RESUMEN
/ SUMMARY: - The story of Rapamune (sirolimus,
rapamycin) began with the isolation of an antibiotic from a soil sample sent to
Ayerst Laboratories in Montreal. More than 25 years later, sirolimus was approved
for use by transplant physicians in the United States. Development programs for
new drugs for transplantation face significant challenges. Four key challenges
were critical to the development of sirolimus as a drug for transplantation:
First, sirolimus was not intended to be an antirejection agent. Second,
sirolimus was not easy to make or purify into a palatable substance for human
use and the development of a pharmaceutical form was an important and critical
hurdle. Third, sirolimus showed potent antirejection activity when tested in de
novo allograft recipients, but the development program required careful
attention to its optimal use in multidrug transplant regimens. Fourth, the
clinical program approved in the United States was rejected in Europe, and it
was only with additional studies and a unique appeal process that sirolimus
became available in Europe. Currently, sirolimus (Rapamune) is available
throughout most of the world except in Japan, having achieved regulatory
approvals in North America, Europe, the Middle East, Latin America, and Asia.
Although sirolimus failed in its original role as an antifungal agent, it
ultimately succeeded as an antirejection drug. Today, sirolimus holds
additional promise both as a drug useful for the prevention of restenosis after
coronary angioplasty and as an antitumor agent. N. Ref:: 39
----------------------------------------------------
[153]
TÍTULO / TITLE: - Cicatricial pemphigoid
in the upper aerodigestive tract: diagnosis and management in severe laryngeal
stenosis.
REVISTA
/ JOURNAL: - Ann Otol Rhinol Laryngol 2003
Mar;112(3):271-5.
AUTORES
/ AUTHORS: - Boedeker CC; Termeer CC; Staats R; Ridder
GJ
INSTITUCIÓN
/ INSTITUTION: - Department of Otorhinolaryngology-Head and
Neck Surgery, Albert-Ludwigs-University, Freiburg, Germany.
RESUMEN
/ SUMMARY: - Pemphigoid is a group of rare, acquired,
autoimmune subepithelial blistering diseases. The condition has been
subclassified into bullous pemphigoid and cicatricial pemphigoid (CP).
Diagnosis is based on clinical presentation, evidence of subepithelialvesicles
or bullae on routine histologic analysis, and direct and indirect
immunofluorescence studies. Cicatricial pemphigoid is characterized by linear
deposition of immunoreactants, principally IgG and complement factor 3, along
epithelial basement membranes. Cicatricial pemphigoid usually leads to mucosal
scarring. We present a case of severe CP that led to laryngeal and subglottic
stenosis and involvement of both eyes and the oral, nasal, and nasopharyngeal
mucosae. Treatment with dapsone, corticosteroids, azathioprine sodium,
cyclosporine A, cyclophosphamide, methotrexate sodium, and mycophenolate
mofetil between 1997 and 2001 only resulted in temporary disease control. The
patient has been treated with leflunomide for the past 8 months, and there have
been no relapses. Treatment of CP with leflunomide has not been described in
the literature until now. N.
Ref:: 25
----------------------------------------------------
[154]
TÍTULO / TITLE: - Molecular diagnosis of
an Enterocytozoon bieneusi human genotype C infection in a moderately
immunosuppressed human immunodeficiency virus seronegative liver-transplant
recipient with severe chronic diarrhea.
REVISTA
/ JOURNAL: - J Clin Microbiol. Acceso gratuito al texto
completo a partir de los 6 meses de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://jcm.asm.org/
●●
Cita: J. Clinical Microbiology: <> 2001 Jun;39(6):2371-2.
AUTORES
/ AUTHORS: - Sing A; Tybus K; Heesemann J; Mathis
A N. Ref:: 5
----------------------------------------------------
[155]
TÍTULO / TITLE: - Rapamycin: friend, foe,
or misunderstood?
REVISTA
/ JOURNAL: - Liver Transpl 2003 May;9(5):469-72.
●●
Enlace al texto completo (gratuito o de pago) 1053/jlts.2003.50101
AUTORES
/ AUTHORS: - Fung J; Marcos A N. Ref:: 19
----------------------------------------------------
[156]
TÍTULO / TITLE: - Eradication of
parvovirus B19 infection after renal transplantation requires reduction of
immunosuppression and high-dose immunoglobulin 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 Oct;17(10):1840-2.
AUTORES
/ AUTHORS: - Liefeldt L; Buhl M; Schweickert B;
Engelmann E; Sezer O; Laschinski P; Preuschof L; Neumayer HH
INSTITUCIÓN
/ INSTITUTION: - Department of Nephrology, Charite,
Humboldt-University Berlin, Germany. lutz.liefeldt@charite.de N. Ref:: 17
----------------------------------------------------
[157]
TÍTULO / TITLE: - Recent advances in
immunosuppressive therapy for renal transplantation.
REVISTA
/ JOURNAL: - Semin Dial 2001 May-Jun;14(3):218-22.
AUTORES
/ AUTHORS: - Peddi VR; First MR
INSTITUCIÓN
/ INSTITUTION: - Division of Nephrology and Hypertension,
Department of Internal Medicine, University of Cincinnati College of Medicine,
Cincinnati, Ohio 45267-0585, USA. ram.peddi@uc.edu
RESUMEN
/ SUMMARY: - Recent advances in immunosuppression have
focused on more effective, safer, and targeted therapies that have resulted in
improved short- and intermediate-term renal allograft survival. During the past
decade there has been a marked decrease in acute rejection rates following
renal transplantation because of the use of newer immunosuppressive agents.
Recent data indicate that the average yearly reduction in the relative hazard
of graft failure beyond 1 year was 4.2% for all recipients (0.4% for those
recipients who had an acute rejection episode and 6.3% for those who did not
have an acute rejection). Despite these improvements the currently available
immunosuppressive agents are associated with significant cardiovascular risk
factors, an increased risk of infection, and the development of malignancies in
the long term. Predictive parameters of donor-specific hyporesponsiveness are
needed so as to allow identification of patients in whom immunosuppressive
therapy can be safely reduced. Immunosuppressive agents that have recently been
approved for use in the United States and those that are in clinical and
preclinical studies are discussed. N.
Ref:: 27
----------------------------------------------------
[158]
TÍTULO / TITLE: - Impact of
immunosuppressive therapy on recurrence of hepatitis C.
REVISTA
/ JOURNAL: - Liver Transpl 2002 Oct;8(10 Suppl
1):S19-27.
●●
Enlace al texto completo (gratuito o de pago) 1053/jlts.2002.35852
AUTORES
/ AUTHORS: - Everson GT
INSTITUCIÓN
/ INSTITUTION: - Hepatology, University of Colorado School
of Medicine, Denver, CO 80262, USA. greg.everson@ucshc.edu
RESUMEN
/ SUMMARY: - 1. Approximately 10% to 25% of hepatitis C
virus-infected recipients of liver allografts will develop cirrhosis within 5
years of transplantation; this acceleration of the natural history of hepatitis
C is caused in part by immunosuppression. 2. Risk factors for aggressive
recurrence, graft loss, and death are treated acute cellular rejection,
methylprednisolone pulse therapy, and use of OKT3. There appears to be no
consistent difference between cyclosporine and tacrolimus in their effects on
hepatitis C. 3. The benefit of steroid withdrawal, although commonly practiced
in transplant recipients with hepatitis C, has not been proven. 4.
Mycophenolate mofetil may show synergistic antiviral properties when used with
interferon; however, posttransplantation use has not been associated with
consistent beneficial or deleterious effects. 5. Effects of other agents, such
as sirolimus or interleukin-2-receptor antibodies, have not been adequately
defined. Early reports suggest that disease activity may be more aggressive
when these agents are constituents of the immunosuppressive regimen. N. Ref:: 54
----------------------------------------------------
[159]
TÍTULO / TITLE: - Limited dose monoclonal
IL-2R antibody induction protocol after primary kidney transplantation.
REVISTA
/ JOURNAL: - Am J Transplant 2002 Jul;2(6):568-73.
AUTORES
/ AUTHORS: - Ahsan N; Holman MJ; Jarowenko MV; Razzaque
MS; Yang HC
INSTITUCIÓN
/ INSTITUTION: - Nephrology and Transplant Division,
University of Medicine and Dentistry of New Jersey, New Brunswick 08904, USA. ahsanna@umdnj.edu
RESUMEN
/ SUMMARY: - This study prospectively compared
immunoprophylaxis with a single intraoperative dose (2 mg/kg) of monoclonal
interleukin-2 receptor (IL-2R) antibody vs. noninduction in kidney transplant
recipients treated with tacrolimus (FK 506), mycophenolate mofetil (MMF) and a
prednisone-based immunosuppression regimen. One hundred recipients of
first-kidney transplant were enrolled into the study to receive either
anti-IL-2R monoclonal antibody, daclizumab (2 mg/kg intraoperatively, limited
anti-IL-2R) or no induction (control). Each patient also received oral
tacrolimus (dosed to target trough level 10-15 ng/mL), MMF (500 mg bid) and
prednisone. The primary efficacy end-point was the incidence of biopsy proven
acute rejection during the first 6 months post-transplant. The patients were
also followed for 12-month graft function, and graft and patient survival
rates. Other than the donor’s age being significantly lower in the control
group, both groups were comparable with respect to age, weight, gender, race,
human leukocyte antigen (HLA)-DR mismatch, panel reactive antibody (%PRA), cold
ischemic time, cytomegalovirus (CMV) status, causes of renal failure, and
duration and modes of renal replacement therapy (RRT). During the first 6
months, episodes of first biopsy confirmed acute rejection was 3/50 (6%) in the
limited anti-IL-2R group and 8/50 (16%) in the controls (p < 0.05).
Twelve-month patient 100/98 (%) and graft survival 100/96 (%) were not
statistically different. The group receiving limited anti-IL-2R did not have
any adverse reactions. Our study demonstrates that a limited (single) 2 mg/kg
immunoprophylaxis dose with monoclonal IL-2R antibody (daclizumab) when
combined with tacrolimus/MMF/steroid allows significant reduction in early
renal allograft rejection to the single digit level. The therapy with
anti-IL-2R antibody is simple and is well tolerated.
----------------------------------------------------
[160]
TÍTULO / TITLE: - The utility of
monoclonal antibody therapy in renal transplantation.
REVISTA
/ JOURNAL: - Transplant Proc 2002 May;34(3):797-800.
AUTORES
/ AUTHORS: - Loertscher R
INSTITUCIÓN
/ INSTITUTION: - Division of Transplantation, McGill
University Health Centre, Montreal, Quebec, Canada. rolf.loertscher@mcgill.ca N. Ref:: 37
----------------------------------------------------
[161]
TÍTULO / TITLE: - Tacrolimus in cardiac
transplantation: efficacy and safety of a novel dosing protocol.
REVISTA
/ JOURNAL: - Transplantation 2002 Oct 27;74(8):1136-41.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000034030.29014.88
AUTORES
/ AUTHORS: - Baran DA; Galin I; Sandler D; Segura L;
Cheng J; Courtney MC; Correa R; Chan M; Fallon JT; Spielvogel D; Lansman SL;
Gass AL
INSTITUCIÓN
/ INSTITUTION: - Zena and Michael A. Weiner Cardiovascular
Institute, Mt. Sinai Medical Center, Box 1030, New York, NY 10029, USA. David.Baran@mountsinai.org
RESUMEN
/ SUMMARY: - BACKGROUND: Although used for more than 20
years, optimal dosing strategies of most immunosuppressants have never been
determined. Tacrolimus, one of the newer agents used in solid-organ
transplantation, is gaining increasing popularity because of its ability to
reverse refractory rejection in cyclosporine-treated patients and its favorable
side-effect profile. As with many other immunosuppressive agents, absorption
and metabolism vary between individuals, which complicates dosing. METHODS: We
hypothesized that a 1-mg dose of tacrolimus may be used to gauge each patient’s
metabolism. A novel dosing scheme was evaluated to establish the safety and
efficacy of this approach. Outcomes were incidence of renal insufficiency and
treatment efficacy as assessed by the rejection grade on the first
endomyocardial biopsy. RESULTS: The risk of renal insufficiency was low, with
only a 3% rise in creatinine at 7 days posttransplant. The risk of renal
insufficiency was highest during the first 3 days of tacrolimus therapy, and
the change in tacrolimus level during this time was identified as the single
best predictor of renal insufficiency. From days 4 to 7, the rise in tacrolimus
level had much less influence on renal function. Ninety-two percent of patients
had a low- or intermediate-grade first cardiac biopsy. CONCLUSIONS: It was
shown that this conservative initial dosing approach, which guarantees renal
safety, is not associated with an increased risk of allograft rejection. We
conclude that administration of tacrolimus via a tailored protocol soon after
transplantation ensures a safe and effective means of immunosuppression.
----------------------------------------------------
[162]
TÍTULO / TITLE: - Recommendations for the
implementation of Neoral C(2) monitoring in clinical practice.
REVISTA
/ JOURNAL: - Transplantation 2002 May 15;73(9
Suppl):S19-22.
AUTORES
/ AUTHORS: - Cole E; Midtvedt K; Johnston A; Pattison
J; O’Grady C
INSTITUCIÓN
/ INSTITUTION: - University of Toronto, Toronto General
Hospital, 621 University Ave., Toronto, Ontario M5G 2C4, Canada.
----------------------------------------------------
[163]
TÍTULO / TITLE: - Safety and efficacy of
TOR inhibitors in pediatric renal transplant recipients.
REVISTA
/ JOURNAL: - Am J Kidney Dis 2001 Oct;38(4 Suppl
2):S22-8.
AUTORES
/ AUTHORS: - Ettenger RB; Grimm EM
INSTITUCIÓN
/ INSTITUTION: - Department of Pediatrics, Mattel
Children’s Hospital at UCLA, Los Angeles, CA 90095-1752, USA. Rettenger@mednet.ucla.edu
RESUMEN
/ SUMMARY: - Information about the pharmacokinetics,
safety, and efficacy of target of rapamycin (TOR) inhibitors, such as sirolimus
and everolimus, in pediatric renal transplant recipients is limited. In an
ascending single-dose pharmacokinetic study of sirolimus in pediatric dialysis
patients, no clinically significant association was observed between patient
age and absorption of sirolimus from the gastrointestinal tract. However, young
pediatric patients (5 to 11 years of age) exhibited significantly greater
apparent oral clearances, suggesting that pediatric patients require slightly
higher doses than do adults when adjusted for body weight or surface area.
Similarly, in studies performed in pediatric renal transplant recipients, the
half-life of sirolimus was shorter and the clearance was greater in younger
patients. On the other hand, in single-dose pharmacokinetic studies of
everolimus, the apparent clearance was reduced in pediatric renal transplant
recipients compared with clearance in adults. This reduced clearance was
attributed to a smaller apparent volume of distribution in pediatric patients,
rather than to a difference in terminal half-life. This suggested that,
although the adult 12-hour dosing interval was appropriate for pediatric
patients, they would require reduced dosing based on body size compared with
adults. In a large trial (N = 719) of sirolimus versus azathioprine in
combination with cyclosporine microemulsion and prednisone, 6 pediatric patients
(13 to 18 years of age) received sirolimus at 2 mg/d, 3 received sirolimus at 5
mg/d, and 3 received azathioprine. Seven of the nine patients who received
sirolimus experienced no rejection episodes. Six infectious episodes occurred
in the 6 patients receiving sirolimus at 2 mg/d, 10 episodes occurred in the 3
patients receiving sirolimus at 5 mg/d, and 8 episodes occurred in the 3
patients receiving azathioprine. At 6 months after transplantation, renal
function was similar in all 3 groups, although there was a statistically
nonsignificant increase in the group receiving sirolimus at 5 mg/d. The mean
cholesterol and triglyceride levels were generally comparable in all 3 groups.
TOR inhibitors are promising agents for the prevention of graft rejection in pediatric
renal transplant recipients, but more pharmacokinetic data are required to
assess the optimal dosing regimens in this population. In addition, further
data are needed on the efficacy and safety of TOR inhibitors in combination
with other agents in pediatric transplantation recipients to best assess the
role of TOR inhibition in corticosteroid and/or calcineurin inhibitor-sparing
regimens. N. Ref:: 13
----------------------------------------------------
[164]
TÍTULO / TITLE: - Low-intensity hematopoietic
stem-cell transplantation across human leucocyte antigen barriers in
dyskeratosis congenita.
REVISTA
/ JOURNAL: - Bone Marrow Transplant 2003
May;31(10):847-50.
●●
Enlace al texto completo (gratuito o de pago) 1038/sj.bmt.1703931
AUTORES
/ AUTHORS: - Dror Y; Freedman MH; Leaker M; Verbeek J;
Armstrong CA; Saunders FE; Doyle JJ
INSTITUCIÓN
/ INSTITUTION: - Marrow Failure and Myelodysplasia
Programme, Division of Haematology and Oncology, Department of Paediatrics, The
Hospital for Sick Children and the University of Toronto, Toronto, Ontario,
Canada.
RESUMEN
/ SUMMARY: - Since the results of conventional
hematopoietic stem-cell transplantation (HSCT) for patients with dyskeratosis
congenita (DC) are poor owing to the high incidence of transplant-related
complications, we explored the use of a low-intensity HSCT regimen. We report
two children with DC with severe cytopenia, who underwent successful HSCT from
a matched unrelated donor after conditioning with fludarabine,
cyclophosphamide, and antithymocyte globulin. Graft-versus-host-disease (GVHD)
prophylaxis consisted of corticosteroids and cyclosporin A. The regimen was
well tolerated, no significant transplant-related complications were observed,
and engraftment was rapid and complete. At 15 and 16 months after HSCT, the
children were fully engrafted, in excellent clinical condition, full-donor
chimerism, and no signs of GVHD. We conclude that a low-intensity regimen is
sufficient to induce durable engraftment using matched unrelated donor HSCT in
DC patients, with minimal 1-year transplant-related toxicity. Longer follow-up
will determine whether this regimen also reduces long-term toxicity. N. Ref:: 35
----------------------------------------------------
[165]
TÍTULO / TITLE: - Tacrolimus versus
cyclosporine after lung transplantation: a prospective, open, randomized
two-center trial comparing two different immunosuppressive protocols.
REVISTA
/ JOURNAL: - J Heart Lung Transplant 2001
May;20(5):511-7.
AUTORES
/ AUTHORS: - Treede H; Klepetko W; Reichenspurner H;
Zuckermann A; Meiser B; Birsan T; Wisser W; Reichert B
INSTITUCIÓN
/ INSTITUTION: - Ludwig-Maximilians-University, Munich,
Germany.
RESUMEN
/ SUMMARY: - BACKGROUND: The need for better
immunosuppressive protocols after lung transplantation led us to investigate
tacrolimus (Tac) in combination with mycophenolate mofetil (MMF) and steroids
or cyclosporine (CsA) in combination with MMF and steroids in a prospective,
open, randomized trial after lung transplantation. METHODS: Between September
1997 and April 1999, 50 lung transplant recipients were randomized to receive
either Tac (n = 26) or CsA (n = 24) in combination with MMF and steroids. All
patients underwent induction therapy with rabbit antithymocyte globulin (ATG)
for 3 days. Freedom from acute rejection (AR), patient survival, infection
episodes, and side effects were monitored. RESULTS: There was no difference in
patient demographics between the two groups. Six-month and 1-year survival was
similar (84.6% and 73.1% in the Tac group vs 83.3% and 79.2% in the CsA group).
Freedom from AR at 6 months and 1 year after lung transplantation was slightly
higher in the Tac group (57.7% and 50% vs 45.8% and 33.3%, p = not significant
[n.s.]), whereas the number of treated rejection episodes per 100 patient days
in the Tac group was significantly lower (0.225 vs 0.426, p < .05). Four
patients in the CsA group had to be switched to Tac. Two patients in the CsA
group had to be retransplanted. Incidence of infections was similar in both
groups with a trend toward more fungal infections in the Tac group (n = 7 vs n
= 1, p = n.s.). CONCLUSIONS: The combination of Tac and MMF seems to have
slightly higher immunosuppressive potential compared with CsA and MMF. The
effectiveness of Tac as a rescue agent is not paralleled with undue signs of
overimmunosuppression.
----------------------------------------------------
[166]
TÍTULO / TITLE: - Donor cell-derived
acute myeloid leukemia developing 14 months after matched unrelated bone marrow
transplantation for chronic myeloid leukemia.
REVISTA
/ JOURNAL: - Bone Marrow Transplant 2001
Oct;28(7):705-7.
●●
Enlace al texto completo (gratuito o de pago) 1038/sj/bmt/1703225
AUTORES
/ AUTHORS: - Hambach L; Eder M; Dammann E; Battmer K;
Stucki A; Heil G; Ganser A; Hertenstein B
INSTITUCIÓN
/ INSTITUTION: - Department of Hematology and Oncology,
Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
RESUMEN
/ SUMMARY: - We report a patient with Ph-positive CML
who developed a Ph-negative AML in donor cells 14 months after BMT from an
HLA-identical male unrelated donor. The Ph translocation could not be detected
by either conventional cytogenetics, FISH or RT-PCR analysis excluding relapse
of CML in myeloid blast crisis. Chimerism studies were performed by variable
number of tandem repeats (VNTR) analysis. These revealed donor-type
hematopoiesis in both unseparated mononuclear cells and CD34+ selected blasts
proving the leukemia to be of donor origin. The patient received three cycles
of polychemotherapy with mitoxantrone, topotecan and ara-c resulting in CR
after the first treatment cycle and reconstitution with donor hematopoiesis. A
second transplant from a female alternative matched unrelated donor was
performed after conditioning with fludarabine and 200 cGy TBI and was well tolerated.
Nine months after the second transplant the patient is at home and in CR. T
cell chimerism was studied by sex chromosome analysis and revealed complete
female donor chimerism. N.
Ref:: 13
----------------------------------------------------
[167]
TÍTULO / TITLE: - Antioxidant nutrients
protect against cyclosporine A nephrotoxicity.
REVISTA
/ JOURNAL: - Toxicology 2003 Jul 15;189(1-2):99-111.
AUTORES
/ AUTHORS: - Parra Cid T; Conejo Garcia JR; Carballo
Alvarez F; de Arriba G
INSTITUCIÓN
/ INSTITUTION: - Unidad de Investigacion, Hospital
Universitario de Guadalajara, C/Donante de Sangre s/n, 19.002 Guadalajara,
España. tparracid@hotmail.com
RESUMEN
/ SUMMARY: - The immunosuppressive drug cyclosporine A (CsA)
has been successfully used in several diseases with immunological basis and in
transplant patients. Nephrotoxicity is the main secondary effect of CsA
treatment. Although the mechanisms of nephrotoxitity are not completely
defined, there is evidence that suggests the role of reactive oxygen species
(ROS) in its pathogenesis. It has been demonstrated in numerous in vivo and in
vitro experiments that CsA induced renal failure and increased the synthesis of
ROS, thromboxane (TX) and lipid peroxidation products in the kidney.
Furthermore, CsA modified the expression and activity of several renal enzymes
(ciclooxygenase, superoxide-dismutase, catalase and glutathione-peroxidase).
Antioxidant nutrients (e.g. Vitamins E and C) can neutralize some of the effects
that CsA produced in the kidney. Thus, Vit E inhibited the synthesis of ROS and
TX and the lipid peroxidation process induced by CsA in kidney structures.
Antioxidants can also improve renal function and histological damage produced
by CsA administration. Although there are few data in humans treated with CsA,
the possibility exists that antioxidants can also neutralize CsA nephrotoxicity
and LDL oxidation. Thus, antioxidant nutrients could have a therapeutic role in
transplant patients treated with CsA. N.
Ref:: 79
----------------------------------------------------
[168]
TÍTULO / TITLE: - Vascular and cellular
mechanisms of chronic renal allograft dysfunction.
REVISTA
/ JOURNAL: - Transplantation 2001 Jun 15;71(11
Suppl):SS37-41.
AUTORES
/ AUTHORS: - Morris RE
INSTITUCIÓN
/ INSTITUTION: - Stanford University School of Medicine,
California, United States. N.
Ref:: 29
----------------------------------------------------
[169]
TÍTULO / TITLE: - Role of prostanoids and
endothelins in the prevention of cyclosporine-induced nephrotoxicity.
REVISTA
/ JOURNAL: - Prostaglandins Leukot Essent Fatty Acids
2001 Apr-May;64(4-5):231-9.
●●
Enlace al texto completo (gratuito o de pago) 1054/plef.2001.0265
AUTORES
/ AUTHORS: - Darlametsos IE; Varonos DD
INSTITUCIÓN
/ INSTITUTION: - Centre Franco-Hellenique de Recherches
Biomedicales, Nikolaos Papanikolaou, Corporation of the Municipality Agrinion,
Agrinion, 30100, Greece. darlamet@otenet.gr
RESUMEN
/ SUMMARY: - Cyclosporine A nephrotoxicity includes
both functional toxicity and histological changes, whose seriousness is
dependent upon the dose and the duration of the drug administration. Several
vasoactive agents have been found to be implicated in cyclosporine induced
nephrotoxicity, among which prostanoids and endothelins are the most important.
In previous studies we were able to prevent the early stage (7 days) of
cyclosporine (37.4 micromol [45 mg]/kg/day) induced nephrotoxicity in rats
either by the administration, i) of OKY-046, a thromboxane A(2)synthase
inhibitor, ii) of ketanserine, an antagonist of S(2)serotonergic,
a(1)adrenergic, and H(1)histaminergic receptors and iii) of nifedipine, a
calcium channel blocker, or by diet supplementation either with evening
primrose oil or fish oil. All these protective agents elevated ratios of
excreted renal prostanoid vasodilators (prostaglandins E(2), 6ketoF(1 alpha))
to vasoconstrictor (thromboxane B(2)), a ratio which was decreased by the
administration of cyclosporine alone. Nifedipine averted the cyclosporine
induced increase of urinary endothelin-1 release. All protections were
associated with the reinstatement of glomerular filtration rate forwards normal
levels whereas renal damage defence, consisting of a decrease of the
cyclosporine induced vacuolizations, was variable. Ketanserine and evening
primrose oil were the only agents which prevented the animal body weight loss.
These data suggest that prostanoids and endothelin-1 may mediate functional
toxicity while thromboxane A(2)is involved the morphological changes too,
provoked in the early stage of cyclosporine treatment. However, other
nephrotoxic factors and additional mechanisms could also be implicated in the
cyclosporine induced nephrotoxicity. N.
Ref:: 91
----------------------------------------------------
[170]
TÍTULO / TITLE: - Role of chiral
chromatography in therapeutic drug monitoring and in clinical and forensic
toxicology.
REVISTA
/ JOURNAL: - Ther Drug Monit 2002 Apr;24(2):290-6.
AUTORES
/ AUTHORS: - Williams ML; Wainer IW
INSTITUCIÓN
/ INSTITUTION: - Department of Oncology, Leicester
University, Leicester, United Kingdom.
RESUMEN
/ SUMMARY: - Advances in chiral chromatographic
separations have given pharmacologists and toxicologists the tools to examine
unexpected clinical results involving chiral drugs. The ability to unravel
complex phenomena associated with drug transport and drug metabolism is
presented in this manuscript. The relation between the chirality of the drug
mefloquine and the intracellular concentrations of the drug cyclosporine is
illustrated by examining the effect of the enantiomers of mefloquine on the
transport activity of P-glycoprotein (Pgp). These studies were conducted using
a liquid chromatographic column containing immobilized Pgp. The results
demonstrated that (+)-mefloquine competitively displaced the Pgp substrate
cyclosporine whereas (-)-mefloquine had no effect on cyclosporine-Pgp binding.
The data suggest that cyclosporine cellular and CNS concentrations can be
increased through the concomitant administration of (+)-mefloquine. The use of
chirality in clinical and forensic situations is also illustrated by the
metabolism of the enantiomers of ketamine (KET). The plasma concentrations of
(+)-KET and (-)-KET and the norketamine metabolites (+)-NK and (-)-NK were
measured in rat plasma using enantioselective gas chromatography. The
separations were accomplished using a gas chromatography chiral stationary phase
based on beta-cyclodextrin. The pharmacokinetic profiles of (+)-, (-)-KET and
(+)-, (-)-NK were determined in control and protein-calorie malnourished (PCM)
rats to determine the effect of PCM on ketamine metabolism and clearance. The
results indicate that PCM produced a significant and stereoselective decrease
in KET and NK metabolism. The data suggest that the effects of environmental
factors (smoking, alcohol use, diet) and drug interactions (coadministered
agents) can be measured using the changes in stereochemical metabolic and
pharmacokinetic patterns of KET and similar drugs. N. Ref:: 33
----------------------------------------------------
[171]
TÍTULO / TITLE: - Ten years of sirolimus
therapy in orthotopic liver transplant recipients.
REVISTA
/ JOURNAL: - Transplant Proc 2003 May;35(3
Suppl):209S-216S.
AUTORES
/ AUTHORS: - Neff GW; Montalbano M; Tzakis AG
INSTITUCIÓN
/ INSTITUTION: - University of Miami, Miami, Florida, USA.
RESUMEN
/ SUMMARY: - BACKGROUND: Sirolimus therapy has been
used in orthotopic liver transplant (OLT) recipients diagnosed with a variety
of diseases; chronic graft rejection (CR), calcineurin associated renal
toxicity, preemptive immune suppression, calcineurin related neurotoxicity,
preemptive therapy in transplant recipients with history of hepatocellular
carcinoma, and steroid resistant allograft rejection. METHODS: A search for the
medical literature and experiences involving sirolimus was done. RESULTS:
Several animal and human reports evaluating the use sirolimus in liver
transplant recipients are found and discussed. CONCLUSION: Sirolimus has been
used for multitude of indications, primarily based on anecdotal experiences.
However, reports of sirolimus related side effects have decreased the
transplant communities’ enthusiasm towards promoting this agent as a safe
immune suppression agent. N.
Ref:: 92
----------------------------------------------------
[172]
TÍTULO / TITLE: - Suggested guidelines
for the use of tacrolimus in cardiac transplant recipients.
REVISTA
/ JOURNAL: - J Heart Lung Transplant 2001
Jul;20(7):734-8.
AUTORES
/ AUTHORS: - Taylor DO; Barr ML; Meiser BM; Pham SM;
Mentzer RM; Gass AL
INSTITUCIÓN
/ INSTITUTION: - Department of Medicine, Division of
Cardiology, University of Utah, Salt Lake City, Utah 84132, USA. N. Ref:: 11
----------------------------------------------------
[173]
TÍTULO / TITLE: - Combined intravenous
pulse methylprednisolone and oral cyclosporine A in the treatment of corneal
graft rejection: 5-year experience.
REVISTA
/ JOURNAL: - Eye 2002 May;16(3):304-8.
●●
Enlace al texto completo (gratuito o de pago) 1038/sj/eye/6700144
AUTORES
/ AUTHORS: - Young AL; Rao SK; Cheng LL; Wong AK; Leung
AT; Lam DS
INSTITUCIÓN
/ INSTITUTION: - Department of Ophthalmology & Visual
Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital,
Shatin, NT, Hong Kong.
RESUMEN
/ SUMMARY: - PURPOSE: To report the mid-term results of
a treatment strategy using topical steroids, intravenous pulse methyl
prednisolone and oral cyclosporine A (CSA) for the treatment of acute corneal
graft rejection. METHODS: Noncomparative, interventional case series. Treatment
of corneal graft rejection included 1% prednisolone eye drops, intravenous
infusion of 500 mg methyl prednisolone, and oral CSA in two regimens—standard
dose was 15 mg/kg/day for 2 days, 7.5 mg/kg/day for 2 days, then adjusted to
maintain trough blood levels of 100-200 microg/l; low dose was 2 mg/kg/day with
no loading dose. RESULTS: Outcome in 34 eyes of 34 patients (21 M;13 F) aged 60
+/- 17.7 years (range 9-83 years), who presented after an average duration of
6.6 +/- 6.3 days (range 0-30 days) following acute corneal graft rejection, are
reported. Twenty-five patients received standard dose CSA while nine patients
received the low dose regimen. Mean duration of treatment before reversal of
graft rejection was 13.6 +/- 12.1 days (range 3-54 days). Treatment was
successful in reversing the graft rejection in 32/34 (94%) eyes. Irreversible
graft failure occurred in one eye in each group. During a mean follow-up period
of 19.2 +/- 16.7 months (range 1-55 months), further episodes of graft
rejection were seen in 1/32 (3%) eyes. Complications due to treatment included:
duodenal ulcer in one patient that responded to medical treatment, and
transient elevation in serum creatinine levels in three patients, which
returned to normal after decrease in dosage or cessation of oral CSA.
CONCLUSION: Our 5-year experience with the use of oral CSA in the treatment of
acute corneal graft rejection has shown this treatment approach to be safe and
effective in reversing the rejection process. This approach may also protect
the graft from subsequent episodes of allograft rejection. A randomised
controlled trial to further delineate the role of CSA in reversing acute graft
rejection seems warranted. N.
Ref:: 17
----------------------------------------------------
[174]
TÍTULO / TITLE: - Diffusion-weighted MR
imaging of posterior reversible leukoencephalopathy syndrome: a pictorial essay.
REVISTA
/ JOURNAL: - Clin Imaging 2003 Sep-Oct;27(5):307-15.
AUTORES
/ AUTHORS: - Kinoshita T; Moritani T; Shrier DA;
Hiwatashi A; Wang HZ; Numaguchi Y; Westesson PL
INSTITUCIÓN
/ INSTITUTION: - Department of Radiology, Division of
Radiology, University of Rochester Medical Center, 601 Elmwood Avenue Box 648,
Rochester, NY 14642, USA. kino@grape.med.tottori-u.ac.jp
RESUMEN
/ SUMMARY: - Posterior reversible leukoencephalopathy
syndrome is characterized by reversible white matter lesions. However, ischemic
injury with irreversible damage may occur. This pictorial essay illustrates MR
features associated with posterior reversible leukoencephalopathy syndrome. We
will emphasize the role of diffusion-weighted imaging for the discrimination of
irreversible ischemic injury from reversible vasogenic edema. N. Ref:: 9
----------------------------------------------------
[175]
TÍTULO / TITLE: - New therapeutic
modalities in the treatment of graft-versus-host disease.
REVISTA
/ JOURNAL: - Crit Rev Oncol Hematol 2001
May;38(2):129-38.
AUTORES
/ AUTHORS: - Basara N; Kiehl MG; Fauser AA
INSTITUCIÓN
/ INSTITUTION: - Clinic of Bone Marrow Transplantation and
Haematology/Oncology, Dr Ottmar-Kohler Str. 2, 55743, Idar Oberstein, Germany. office@bmt-center-io.com
RESUMEN
/ SUMMARY: - Acute and chronic GvHD are still a major
concern in allogeneic hematopoietic stem cell transplantation, still
contributing substantially to morbidity and mortality in this therapeutic
procedure. Over the past decade, many advances have been made with regard to
the prevention and treatment of GvHD using various drugs such as cyclosporine
A, FK506, mycophenolate mofetil and/or monoclonal IL-2 receptor antagonists.
Despite these measurements with regard to the prevention of acute GvHD, it is
very difficult to treat these clinical conditions successfully. However, if
patients do not experience any GvHD often the desired effect of graft versus
leukemia (GvL) remains absent increasing the probability of a relapse, in
particular, in patients transplanted, which are considered at higher risk for
relapse. At the present time, new strategies in the prevention of acute GvHD
are in progress in particular the use of genetic manipulated donor T cells
expressing suicide genes. Further clinical and laboratory studies are required
in order to improve the prevention and, in particular, the therapy of
established GvHD. N.
Ref:: 84
----------------------------------------------------
[176]
TÍTULO / TITLE: - New strategies to
reduce nephrotoxicity.
REVISTA
/ JOURNAL: - Transplantation 2001 Dec 27;72(12
Suppl):S99-104.
AUTORES
/ AUTHORS: - Kreis H
RESUMEN
/ SUMMARY: - Since the introduction of cyclosporine,
CNIs have formed the basis of immunosuppressive therapy in renal
transplantation. The propensity of these agents to ultimately damage the very
organs they were intended to protect was always recognized, but largely ignored
due to their impressive ability to improve short-term outcomes. With the
availability of equally powerful new immunosuppressive agents devoid of major
nephrotoxicity, the irony of this situation has become all too apparent, and
investigators are beginning to reevaluate the role of CNIs in renal
transplantation. In this paper, we looked at strategies using MMF or sirolimus
to reduce, withdraw, or replace CNIs in renal transplantation. Although MMF has
proved effective in combination with CNIs, particularly in reducing acute
rejection rates, its use as base therapy to allow CNI therapy to be withdrawn
or eliminated is questionable. On the basis of initial trials, sirolimus holds
promise for use as base therapy. To date, it is probably the only agent used in
renal transplantation that provides immunosuppression comparable to
cyclosporine or tacrolimus, which may someday allow sirolimus to replace. CNIs
or allow early withdrawal of CNI therapy. Further study is needed to better
clarify the role of sirolimus in improving long-term renal transplantation
outcomes. N. Ref:: 61
----------------------------------------------------
[177]
TÍTULO / TITLE: - Monitoring of cellular
resistance to cancer chemotherapy.
REVISTA
/ JOURNAL: - Hematol Oncol Clin North Am 2002
Apr;16(2):357-72, vi.
AUTORES
/ AUTHORS: - Krishan A; Arya P
INSTITUCIÓN
/ INSTITUTION: - Radiation Oncology Department, University
of Miami Medical School, Division of Experimental Therapeutics (R-71), P.O. Box
01690, Miami, FL 33101, USA. akrishan@med.miami.edu
RESUMEN
/ SUMMARY: - Cellular resistance to a broad spectrum of
natural products used as antitumor drugs is believed to be a major cause for
the failure of chemotherapy. Flow cytometry has been used for monitoring the
expression of drug resistance markers, determining accumulation of fluorescent
drugs, and for screening of drugs that enhance chemosensitivity by blocking
efflux and enhancing drug retention. This article reviews recent developments
in our understanding of the multiple drug resistance phenotype and the use of
flow cytometry for the study of drug efflux and its modulation in human tumor
cells. N. Ref:: 77
----------------------------------------------------
[178]
TÍTULO / TITLE: - Sirolimus therapy in
cardiac transplantation.
REVISTA
/ JOURNAL: - Transplant Proc 2003 May;35(3
Suppl):171S-176S.
AUTORES
/ AUTHORS: - Radovancevic B; Vrtovec B
INSTITUCIÓN
/ INSTITUTION: - Texas Heart Institute at St. Luke’s
Episcopal Hospital, Houston, Texas, USA.
RESUMEN
/ SUMMARY: - Rapamycin powerfully inhibits the
progression of antigen-activated T cells through the cell cycle. In animal
heart transplantation models, rapamycin therapy has been associated with
profound immunosuppressive effects on host humoral and cellular responses. In
consequence, further studies have been conducted to evaluate the efficiency of
rapamycin in preventing acute heart allograft rejection, treating refractory
acute heart allograft rejection, inducing transplantation tolerance, and
preventing and treating transplant coronary artery disease. The results of
these studies indicated that rapamycin can effectively prevent acute graft
rejection and inhibit refractory acute graft rejection in heart transplant
recipients by exerting potent immunosuppressive and antiproliferative effects
without adversely affecting renal function. This supports the use of rapamycin
therapy in heart transplant recipients, especially in those with renal
dysfunction, for whom treatment with calcineurin inhibitors is contraindicated.
Rapamycin may also halt and even reverse the progression of cardiac allograft
vasculopathy, which warrants further clinical trials in humans. Finally,
rapamycin may be able to induce transplantation tolerance, thus making it one
of the most promising modalities for improving the long-term survival of heart
transplant recipients. N.
Ref:: 41
----------------------------------------------------
[179]
TÍTULO / TITLE: - Pimecrolimus (Elidel,
SDZ ASM 981)--preclinical pharmacologic profile and skin selectivity.
REVISTA
/ JOURNAL: - Semin Cutan Med Surg 2001
Dec;20(4):233-41.
AUTORES
/ AUTHORS: - Stuetz A; Grassberger M; Meingassner JG
INSTITUCIÓN
/ INSTITUTION: - Novartis Research Institute, Vienna,
Austria.
RESUMEN
/ SUMMARY: - The ascomycin macrolactam derivative
pimecrolimus (Elidel, SDZ ASM 981; Novartis Pharma AG, Basel Switzerland) is a
cell-selective inhibitor of inflammatory cytokines specifically developed for
the treatment of inflammatory skin diseases, such as atopic dermatitis,
allergic contact dermatitis, irritant contact dermatitis, and plaque-type
psoriasis. It inhibits the production of inflammatory cytokines in T cells and
mast cells and prevents the release of preformed inflammatory mediators from
mast cells. Topically administered pimecrolimus is as effective as the
high-potency corticosteroid clobetasol-17-propionate in a pig model of allergic
contact dermatitis (ACD). Unlike clobetasol, however, it does not cause skin
atrophy. Given orally, pimecrolimus is as potent or superior to tacrolimus (FK
506) in treating ACD in mice and rats. Pimecrolimus also effectively reduces
skin inflammation and pruritus in hypomagnesemic hairless rats, a model that
mimics acute signs of atopic dermatitis. Pimecrolimus shows only a low
potential to impair systemic immune responses when compared with tacrolimus as
shown in rats in (1) the localized graft-versus-host reaction, (2) the antibody
formation to sheep red blood cells, and (3) kidney transplantation.
Pimecrolimus permeates through pig skin in vitro at a 10-times lower rate than
tacrolimus, indicating a lower potential for percutaneous absorption in vivo.
The data suggest that pimecrolimus combines high anti-inflammatory activity in
the skin with a low potential to impair systemic immune reactions. N. Ref:: 31
----------------------------------------------------
[180]
TÍTULO / TITLE: - Molecular actions of
sirolimus: sirolimus and mTor.
REVISTA
/ JOURNAL: - Transplant Proc 2003 May;35(3
Suppl):227S-230S.
AUTORES
/ AUTHORS: - Kirken RA; Wang YL
INSTITUCIÓN
/ INSTITUTION: - Department of Integrative Biology and
Pharmacology, The University of Texas Health Science Center at Houston,
Houston, Texas 77030, USA. robert.a.kirken@uth.tmc.edu
RESUMEN
/ SUMMARY: - Recent therapeutic strategies to combat
organ allograft rejection have focused on T-cell signaling pathways and the
molecules that comprise them. The macrolide antibiotic produced by the
bacterium Streptomyces hygroscopicus, known as sirolimus or rapamycin, has
shown great therapeutic potential in the transplant setting. Sirolimus alone or
in combination with other immunosuppressive agents can block acute rejection,
chronic graft destruction, and promote permanent allograft acceptance.
Sirolimus targets a unique serine-threonine kinase, mammalian target of
rapamycin (mTor), which plays a key role in mitogenic and nutritional cells
signals. Within T cells, mTor regulates a number of proteins likely dependent
on T cell growth factors such as interleukin 2. This review is focused on the
molecular mechanisms by which mTor may regulate T-cell signaling cascades and
affect T-cell responsiveness, and how sirolimus likely uncouples this
activity. N. Ref:: 32
----------------------------------------------------
[181]
TÍTULO / TITLE: - Treatment of patients
with chronic idiopathic urticaria.
REVISTA
/ JOURNAL: - Clin Rev Allergy Immunol 2002
Oct;23(2):233-41.
AUTORES
/ AUTHORS: - Stanaland BE
INSTITUCIÓN
/ INSTITUTION: - Division of Allergy and Immunology,
University of South Florida Health Sciences Center, USA.
RESUMEN
/ SUMMARY: - Treatment of patients with chronic
idiopathic urticaria (CIU) involves reducing symptoms with the least invasive
therapy and carefully balancing risk and benefit. The mainstay of therapy is
the use of antihistamines with or without the use of intermittent pulses of
corticosteroids. Alternative therapies to chronic corticosteroids include
leukotriene antagonists, plasma-phoresis, dapsone, stanazolol,
hydroxychloroquine, methotrexate, cyclosporin, tacrolimus, and warfarin. A
practical approach to CIU bases treatment and severity on the patients’
previous response to therapy. Therapy goals are to reduce symptoms until
spontaneous resolution occurs. Management of CIU patients can be both
frustrating and rewarding. N.
Ref:: 34
----------------------------------------------------
[182]
TÍTULO / TITLE: - Long-term kidney
transplant survival.
REVISTA
/ JOURNAL: - Am J Kidney Dis 2001 Dec;38(6 Suppl
6):S44-50.
AUTORES
/ AUTHORS: - Hariharan S
INSTITUCIÓN
/ INSTITUTION: - Froedert Memorial Hospital, Medical
College of Wisconsin, Milwaukee, WI 53226, USA. hari@mcw.edu
RESUMEN
/ SUMMARY: - With improvements in short-term kidney
graft survival, focus has shifted towards long-term survival. There has also
been a substantial improvement in long-term survival as measured by kidney
half-life. Long-term graft failure is secondary to chronic allograft
nephropathy (CAN), recurrent disease, and death with a functioning graft. CAN
is secondary to a combination of chronic rejection, chronic cyclosporine
toxicity, and/or donor kidney disease. Risk factors for chronic rejection have
been attributed to both immunological and nonimmunological causes. With a
marked reduction in acute rejection rates-an important risk factor for
CAN-there is a substantial improvement in kidney half-life. There are still
nonimmunological factors, such as donor age, that adversely affect long-term
graft survival. In addition, African-American recipients continue to have a
shorter graft half-life. Recurrent disease is becoming an important cause of
late graft failure. Despite the introduction of various potent
immunosuppressive agents, there has been little or no impact on the prevalence
as well as progression of recurrent diasease. With the reduction of acute
rejection rates and improved short- and long-term graft survival, further
improvements of long-term graft survival will be an important focus in the 21st
century. N. Ref:: 45
----------------------------------------------------
[183]
TÍTULO / TITLE: - Intestinal
graft-versus-host disease: mechanisms and management.
REVISTA
/ JOURNAL: - Drugs 2003;63(1):1-15.
AUTORES
/ AUTHORS: - Takatsuka H; Iwasaki T; Okamoto T;
Kakishita E
INSTITUCIÓN
/ INSTITUTION: - Second Department of Internal Medicine,
Hyogo College of Medicine, Hyogo, Japan. hematol@hyo-med.ac.jp
RESUMEN
/ SUMMARY: - Allogeneic haematopoietic stem cell
transplantation remains the treatment of choice for a number of malignancies.
However, graft-versus-host disease (GVHD) has long been regarded as a serious
complication of this procedure. Although GVHD may affect any organ, intestinal
GVHD is particularly important because of its frequency, severity and impact on
the general condition of the patient. Recent studies have led to progressive
elucidation of the mechanism of GVHD. Donor T cells are critical for the
induction of GVHD, because depletion of T cells from bone marrow grafts
effectively prevents GVHD but also results in an increase of leukaemia relapse.
It has been shown that the gastrointestinal tract plays a major role in the
amplification of systemic disease because gastrointestinal damage increases the
translocation of endotoxins, which promotes further inflammation and additional
gastrointestinal damage. Consequently, the management of intestinal GVHD (and
the intestine itself) is a subject that should be highlighted. In this article,
approaches to the prevention of intestinal GVHD are discussed after being
classified into three categories: regimens in common clinical use, regimens
under investigation and original regimens used at our hospital. The standard
regimen that is used most widely for prevention of GVHD is cyclosporin plus
short-term methotrexate. Corticosteroids can be added to this regimen but
careful consideration of the adverse effects of these hormones should be
considered. Tacrolimus is a newer, more potent alternative to cyclosporin.
T-cell depletion (TCD) after transplantation has been shown to prevent acute
GVHD, however, the survival benefit of TCD has not been as great as expected.
Mycophenolate mofetil can be useful for the treatment of acute GVHD as part of
combination therapy. Regimens currently under investigation in animal
experiments include suppression of inflammatory cytokines and inhibition of
T-cell activation, and, specifically at our institution, hepatocyte growth
factor gene therapy. The evidence-based therapy used at our institution includes
systemic antibacterial therapy (including eradication of intestinal bacteria)
to prevent the intestinal translocation of lipopolysaccharide and avoid the
subsequent increase of various inflammatory cytokines. In addition, because of
the similarities between intestinal GVHD and ulcerative colitis, sulfasalazine,
betamethasone enemas and eicosapentaenoic acid have been used to treat
intestinal GVHD in some patients. N.
Ref:: 125
----------------------------------------------------
[184]
TÍTULO / TITLE: - The mosaic of
immunosuppressive drugs.
REVISTA
/ JOURNAL: - Mol Immunol 2003 Jul;39(17-18):1073-7.
AUTORES
/ AUTHORS: - Masri MA
INSTITUCIÓN
/ INSTITUTION: - Rizk Hospital, P.O Box 11-3288, Beirut,
Lebanon. marwan.masri@mysalima.com
RESUMEN
/ SUMMARY: - Graft rejections as well as tolerance are
true representation of the specificity, sophistication and redundancy of an
elegantly and meticulously designed immune system. Tolerance is in a way
similar to the process of self-recognition where lymphoid clones, during
development, baring self-reactive receptor are eliminated or rendered in active
by “clonal deletion” leading to a state of accommodation and acceptance
(anergic). On the other hand, both acute and chronic rejections are
manifestation of the purpose of existence of the immune system, which is to
defend the host against foreign invaders. Thus, in order to treat (control)
graft rejection it is necessary to determine and understand the steps leading to
recognition, stimulation, activation, and amplification of the immune system.
The first step leading to the initiation of the immune system cascade is
recognition. Which can either be direct where donor antigens of the major
histocompatibility complex (MHC) expressed on the donor cells (passenger
leukocytes) or tissues are recognised by the host immune system. The direct
recognition pathway initiates acute graft rejection. Alternatively processed
donor MHC peptides presented by the recipient antigen presenting cells (APC)
initiate the indirect pathway of immune response, which is as important as the
direct recognition especially in chronic rejection. Recognition is followed by
the ligation of a series of adhesion molecules starting with an antigen to its
specific T-cell receptor (TCR)/cluster of differentiation (CD) complex,
expressed on the surface of the T cell. In order for the activation to precede
additional costimulatory signals, such as ligation of the CD28/B7, CD4/HLA
class II and CD/HLA class I antigens are required. The activation process is
accompanied by an increase of cytokines production such as interleukin (IL)-2,
IL-12, interferon (INF) and tumour necrosis factor (TNF) by the primed T cell.
The complexity and the polymorphic nature of the immune system have
necessitated designing agents that inhibit the immune system at different
levels. Cyclosporine and Tacrolimus, collectively known as calcineurin
inhibitors, seems to act on the IL-2 by inhibiting its production thus leading
to a decrease in the proliferation of the activated lymphocyte. Rapamycin,
which is similar to Tacrolimus, inhibits graft rejection by blocking IL-2
activation and phosphorylation of 70 S6 kinase thus inhibiting the progression
of T-cell from G to S phase. While Cellcept (MMF) reduce the proliferation of T
cell by inhibiting purine synthesis and by its action on ionosine monophosphate
dehydrogenase. Anti-lymphocyte antibodies (ATG) deplete circulating lymphocytes
while selective monoclonal antibodies are directed against IL-2 receptor thus
reducing the rate of proliferation of activated T cells. Recently, antibodies
to the CD40/CD40 ligand have been shown to induce long-term graft survival with
the inhibition of the Th1 cytokines (INF), IL-2 and IL-12 and upregulating the
Th2 cytokines IL-4 and IL-10. Lastly graft rejection can be reduced by blockade
of the B7/CD28 costimulation pathway with the fusion protein CTLA-4Ig. With the
availability of such potent and diverse agents it is now possible to develop
multi drug regiments that can depress the immune system at the different steps
of the activation cascade, with minimal side effects, thus improving graft and
patient survival rates. N.
Ref:: 73
----------------------------------------------------
[185]
TÍTULO / TITLE: - Prevention strategies
for type 1 diabetes mellitus: current status and future directions.
REVISTA
/ JOURNAL: - BioDrugs 2003;17(1):39-64.
AUTORES
/ AUTHORS: - Winter WE; Schatz D
INSTITUCIÓN
/ INSTITUTION: - Department of Pathology, University of
Florida, Gainesville, Florida 32610, USA. winter@pathology.ufl.edu
RESUMEN
/ SUMMARY: - Type 1 diabetes mellitus affects about 1
in 300 people in North America and Europe. Epidemiological studies indicate
that the incidence and thus prevalence of type 1 diabetes is rising worldwide.
Intervention in autoimmune type 1a diabetes could occur at the time of
diagnosis or, preferably, prior to clinical presentation during the
‘prediabetic’ period (e.g. prevention). Prediabetes is best recognised by the
detection of islet autoantibodies in the serum. Promising intervention
strategies include monoclonal antibody therapies (e.g. anti-CD3, anti-CD25,
anti-CD52 or anti-CD20 monoclonal antibodies), immunosuppression (e.g. calcineurin
inhibitors, B7 blockade, glucocorticoids, sirolimus (rapamycin), azathioprine
or mycophenolate mofetil), immunomodulatory therapies (e.g. plasmapheresis,
intravenous immunoglobulin, cytokine administration, adoptive cellular gene
therapy) and tolerisation interventions (e.g. autoantigen administration or
avoidance, altered peptide ligand or peptide-based therapies). To date, islet
and pancreas transplantation have essentially been reserved for patients with
long-standing diabetes who have complications and are also in need of a
concurrent kidney transplant. None of the therapies attempted to date has
produced long-term remissions in new-onset type 1 diabetes patients and no
therapies have been shown to prevent the disease. Nevertheless, with advances
in our understanding of basic immunology and the cellular and molecular
mechanisms of tolerance induction and maintenance, successful intervention
therapies will be developed. The balance between safety and efficacy is
critical. Higher rates of adverse events might be more tolerable in new-onset
type 1 diabetes patients if the therapy is extremely effective at inducing a
permanent remission. However, therapies must not harm the beta-cells themselves
or any organ system that is a potential target of diabetes complications, such
as the nervous system, retina, cardiovascular system or kidney. In the
treatment of prediabetes, successful therapies should provide a level of safety
similar to that of currently used vaccines and a high level of efficacy. N. Ref:: 244
----------------------------------------------------
[186]
TÍTULO / TITLE: - Tailoring
immunosuppressive therapy based on donor and recipient risk factors.
REVISTA
/ JOURNAL: - Transplant Proc 2001 May;33(3):2207-11.
AUTORES
/ AUTHORS: - First MR
INSTITUCIÓN
/ INSTITUTION: - University of Cincinnati Medical Center,
Cincinnati, Ohio 45267-0585, USA. N.
Ref:: 35
----------------------------------------------------
[187]
TÍTULO / TITLE: - Cytokine and
immunosuppressive therapies of type 1 diabetes mellitus.
REVISTA
/ JOURNAL: - Endocrinol Metab Clin North Am 2002
Jun;31(2):477-95.
AUTORES
/ AUTHORS: - Gottlieb PA; Hayward AR
INSTITUCIÓN
/ INSTITUTION: - Barbara Davis Center for Childhood
Diabetes, Department of Pediatrics, University of Colorado Health Sciences
Center, Box B140, 4200 East 9th Ave., Denver, CO 80262, USA.
RESUMEN
/ SUMMARY: - In this article, the authors covered a
number of issues that affect how researchers approach prevention of diabetes.
The focus has been the use of cytokines and immunosuppressive therapies. The
historical understanding of cytokine and immunosuppressive approaches, new
developments in using these agents in humans, and the issues involved in
designing diabetes prevention trials were reviewed. Although progress at times
appears slow, the current research activities predict new developments in the
next few years that may improve the understanding of the progression of
diabetes and possible ways to intervene.
N. Ref:: 79
----------------------------------------------------
[188]
TÍTULO / TITLE: - Maintenance
immunosuppression in the renal transplant recipient: an overview.
REVISTA
/ JOURNAL: - Am J Kidney Dis 2001 Dec;38(6 Suppl
6):S25-35.
AUTORES
/ AUTHORS: - Gaston RS
INSTITUCIÓN
/ INSTITUTION: - Division of Nephrology, University of
Alabama at Birmingham, Birmingham, AL 35294, USA. rgaston@nrtc.uab.edu
RESUMEN
/ SUMMARY: - Managing maintenance immunosuppressive
regimens after kidney transplantation is often challenging and confusing,
requiring careful attention to efficacy, dosing, adverse effects, and costs of
multiple medications. Most protocols combine a primary immunosuppressant
(cyclosporine or tacrolimus) with one or two adjunctive agents (azathioprine,
mycophenolate mofetil, sirolimus, corticosteroids). Avoiding drug-drug
interactions is a major part of effective immunosuppressant management, and
special situations (eg, pregnancy, intravenous dosing, caring for minority
patients) can prove especially daunting. This review summarizes available data
regarding current practices in maintenance immunosuppression, emphasizing
issues that arise in day-to-day management of renal transplant recipients. N. Ref:: 69
----------------------------------------------------
[189]
TÍTULO / TITLE: - Regulation of
endothelial-type NO synthase expression in pathophysiology and in response to
drugs.
REVISTA
/ JOURNAL: - Nitric Oxide 2002 Nov;7(3):149-64.
AUTORES
/ AUTHORS: - Li H; Wallerath T; Munzel T; Forstermann U
INSTITUCIÓN
/ INSTITUTION: - Department of Pharmacology, Johannes
Gutenberg University, Obere Zahlbacher Strasse 67, D-55101, Mainz, Germany.
RESUMEN
/ SUMMARY: - In many types of cardiovascular
pathophysiology such as hypercholesterolemia and atherosclerosis, diabetes,
cigarette smoking, or hypertension (with its sequelae stroke and heart failure)
the expression of endothelial NO synthase (eNOS) is altered. Both up- and
downregulation of eNOS have been observed, depending on the underlying disease.
When eNOS is upregulated, the upregulation is often futile and goes along with
a reduction in bioactive NO. This is due to an increased production of
superoxide generated by NAD(P)H oxidase and by an uncoupled eNOS. A number of
drugs with favorable effects on cardiovascular disease upregulate eNOS
expression. The resulting increase in vascular NO production may contribute to
their beneficial effects. These compounds include statins,
angiotensin-converting enzyme inhibitors, AT1 receptor antagonists, calcium
channel blockers, and some antioxidants. Other drugs such as glucocorticoids,
whose administration is associated with cardiovascular side effects,
downregulate eNOS expression. Stills others such as the immunosuppressants
cyclosporine A and FK506/tacrolimus or erythropoietin have inconsistent effects
on eNOS. Thus regulation of eNOS expression and activity contributes to the
overall action of several classes of drugs, and the development of compounds
that specifically upregulate this protective enzyme appears as a desirable target
for drug development. N.
Ref:: 201
----------------------------------------------------
[190]
TÍTULO / TITLE: - Novel
pharmacotherapeutic approaches to prevention and treatment of GVHD.
REVISTA
/ JOURNAL: - Drugs 2002;62(6):879-89.
AUTORES
/ AUTHORS: - Jacobsohn DA; Vogelsang GB
INSTITUCIÓN
/ INSTITUTION: - Oncology and Pediatrics, The Johns Hopkins
University School of Medicine, Baltimore, Maryland, USA. jacobda@jhmi.edu
RESUMEN
/ SUMMARY: - Acute and chronic graft versus host
disease (GVHD) remain the major barriers to successful hematopoietic cell
transplantation. The induction of GVHD may be divided into three phases:
recipient conditioning;donor T-cell activation; andeffector cells mediating
GVHD. This review examines GVHD prevention and treatment using this conceptual
model as framework. The various pharmacological agents discussed impact on
different phases of the GVHD cascade. For example, keratinocyte growth factor
and interleukin (IL)-11 are cytokines that may be useful in disrupting phase I
of the GVHD cascade by blocking gastrointestinal tract damage, and lowering
serum levels of lipopolysaccharide and tumour necrosis factor (TNF)-alpha.
Cyclosporin, tacrolimus (FK-506) and sirolimus (rapamycin) are some of the main
agents that disrupt phase II (donor T-cell activation). Mycophenolate mofetil
and tresperimus probably act on this phase as well. Other novel drugs that
affect phase II are tolerance-induction agents such as CTLA-4 and anti-CD40-ligand
monoclonal antibodies, and preliminary results using CTLA-4 monoclonal antibody
in GVHD prevention are encouraging. Examples of agents that disrupt phase III
are the IL-2 receptor antagonist daclizumab and the anti-TNFalpha monoclonal
antibody infliximab. These anti-cytokine antibodies have shown promising
results in early studies. The most effective approach to GVHD prevention will
probably be a combination regimen where the three phases of the GVHD cascade
are disrupted. Once GVHD has occurred, all three phases of the cascade are
activated. Developments of combination therapy for treatment of both acute and
chronic GVHD are likely to yield better results than monotherapy. The numerous
new treatment modalities presented should improve the outlook for patients with
acute and chronic GVHD. N.
Ref:: 74
----------------------------------------------------
[191]
TÍTULO / TITLE: - What’s in the pipeline?
New immunosuppressive drugs in transplantation.
REVISTA
/ JOURNAL: - Am J Transplant 2002 Nov;2(10):898-903.
AUTORES
/ AUTHORS: - Vincenti F
INSTITUCIÓN
/ INSTITUTION: - University of California, San Francisco,
Kidney Transplant Service, 505 Parnassus Avenue, Room 884M, San Francisco, CA
94143-0116, USA. vincentif@surgery.ucsf.edu
RESUMEN
/ SUMMARY: - In the pipeline, there are a number of
novel immunosuppressive drugs in preclinical development or in early clinical
trials. The major target of new agents are cell-surface molecules important in
immune cell interactions (especially the costimulatory pathway), signaling
pathways that activate T cells, T-cell proliferation and trafficking and
recruitment of immune cells responsible for rejection. The most promising
biologic agents include a humanized anti-CD11a (anti-LFA1), humanized
anti-B7.1/B7.2, a second-generation CTLA4Ig (LEA29Y) and a humanized antibody
to anti-CD45 RB. Inhibitors of T-cell activation and signaling are still in
preclinical development. The most interesting inhibitors of T-cell proliferation
include inhibitors of the Janus protein tyrosine kinase, JAK3, and FK778, a
leflunomide analog. Chemokines play an important role in rejection by virtue of
their critical role as regulator of trafficking and activation of lymphocytes.
Early trials of FTY720, a synthetic small molecule with functional homology to
sphingosine-1 phosphate leading to lymphocyte sequestration, appear very
promising; however, enthusiasm for this drug is mitigated by its potential
cardiac side-effects. Antagonists to several chemokine receptors, including
CCR1, CXCR3 and CCR5, have been shown to be effective in experimental
transplantation and are likely to be considered for clinical development. N. Ref:: 46
----------------------------------------------------
[192]
TÍTULO / TITLE: - Current and potential
agents for the treatment of alopecia areata.
REVISTA
/ JOURNAL: - Curr Pharm Des 2001 Feb;7(3):213-30.
AUTORES
/ AUTHORS: - Freyschmidt-Paul P; Hoffmann R; Levine E;
Sundberg JP; Happle R; McElwee KJ
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology, Philipp
University, Marburg, Germany. freyschm@mailer.uni-marburg.de
RESUMEN
/ SUMMARY: - Alopecia areata is considered to be a
T-cell mediated autoimmune disease of the hair follicle. Current
immunosuppressive approaches and immunomodulatory treatment with contact
sensitizers such as diphenylcyclopropenone and squaric acid dibutylester are
dealt with in this review article. The efficacy of the various modes of treatment
is evaluated by a review of literature and their mode of action is discussed.
In accordance with the mechanism of autoimmune pathogenesis of AA, improved
future treatments may be immunosuppressive or immunomodulatory, or they should
otherwise protect the hair follicle from the injurious effects of the
inflammation. Such possible future therapeutic approaches include the use of
liposomes as an improved vehicle, application of immunosuppressive cytokines
like TGF-beta and IL-10, inhibition of apoptosis mediated by the Fas-FasL
system, inhibition of the lymphocyte homing receptor CD44v10, induction of
tolerance as well as principles of gene therapy. N. Ref:: 141
----------------------------------------------------
[193]
TÍTULO / TITLE: - Oral lichen planus: an
update.
REVISTA
/ JOURNAL: - Drugs Today (Barc) 2002 Aug;38(8):533-47.
AUTORES
/ AUTHORS: - Agarwal R; Saraswat A
INSTITUCIÓN
/ INSTITUTION: - Pharmaceutics Research Division,
University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh,
India. ravindra_angarwal1@yahoo.com
RESUMEN
/ SUMMARY: - Oral lichen planus (OLP) is a chronic
autoimmune disease of unknown etiology that affects the skin and mucosae,
including the oral cavity. The disease is characterized by lacy, thin white
lines on a violaceous background on the oral mucosa, usually on the inside of
the cheeks. The disease is also characterized by chronic inflammation and is
often associated with severe pain and a burning sensation in the mouth. The
etiopathogenesis of lichen planus is complex, with the involvement of T
lymphocytes, mast cells, intercellular adhesion molecule-1 (ICAM-1) and major
histocompatibility complex class II antigens. The immunologic process results in
vacuolar degeneration, lysis of basal cells and, ultimately, liquefaction of
the basal cells. The precipitating factors of OLP can be: stress, particular
foods, dental plaque, systemic illness and poor oral hygiene. Often no
medication is necessary for benign disease. In the case of severe pain and the
burning sensation, high potency topical corticosteroids remain the most
reliably effective treatment. Other available treatments are topical
cyclosporine, tacrolimus, retinoids and other immunosuppressive agents.
Systemic corticosteroids may be indicated in patients whose condition is
unresponsive to topical corticosteroids. However, OLP remains a challenging
disease to treat, in spite of the numerous treatments tried in the patient
population. N. Ref:: 120
----------------------------------------------------
[194]
TÍTULO / TITLE: - Early clinical
experience with a novel rapamycin derivative.
REVISTA
/ JOURNAL: - Ther Drug Monit 2002 Feb;24(1):53-8.
AUTORES
/ AUTHORS: - Nashan B
INSTITUCIÓN
/ INSTITUTION: - Klinik fur Viszeral-und
Transplantationschirurgie, Medizinische Hochschule Hannover, Hannover, Germany.
nashan@tx-amb.mh-hannover.de
RESUMEN
/ SUMMARY: - SDZ RAD (everolimus, Certican is a novel
macrolide immunosuppressant that blocks growth factor-driven transduction
signals in the T-cell response to alloantigen. After stimulation of the IL-2
receptor on the activated T-cell, SDZ RAD inhibits p70S6 kinase, acting at a
later stage in the T-cell mediated response than do cyclosporine and other
calcineurin inhibitors (CNIs). Unlike the CNIs, SDZ RAD is a proliferation
signal inhibitor, blocking growth factor-driven proliferation of both
hematopoietic and nonhematopoietic cells. These activities are complementary to
those of cyclosporine and provide a rationale for the addition of SDZ RAD to
cyclosporine-based immunosuppression, with the potential for minimizing CNI
nephrotoxicity, reducing the incidence of acute rejection, and favoring
long-term graft survival. Potential also exists for beneficial effects on other
factors that may influence the development of chronic rejection. These factors
include comorbid diseases such as hypertension, which may affect transplant
vasculopathy, and opportunistic infection with cytomegalovirus (CMV) and other
viruses, which may increase the risk of chronic rejection. The synergistic
effect of SDZ RAD and cyclosporine has been confirmed in preclinical models,
with graft survival being significantly prolonged in rat models of kidney and
heart allotransplantation. Clinical experience with SDZ RAD in
cyclosporine-based immunosuppression, including low-dose cyclosporine regimens,
has also resulted in predictable and favorable clinical outcomes. Low rates of
acute rejection, excellent rates of patient and graft survival, lower incidence
of CMV infections, better cholesterol, triglyceride and creatinine profiles,
and better renal function have been demonstrated with SDZ RAD and lower doses
of cyclosporine (Neoral; Novartis) in recipients of renal transplants. These
findings, combined with good tolerability rates and an acceptable side-effect
profile, indicate that the synergistic profile of SDZ RAD in combination with
nontoxic dosages of CNI’s and IL2 inhibitors will further improve longterm
results in renal transplantation. N.
Ref:: 48
----------------------------------------------------
[195]
TÍTULO / TITLE: - Tolerance to islet
autoantigens in type 1 diabetes.
REVISTA
/ JOURNAL: - Annu Rev Immunol 2001;19:131-61.
●●
Enlace al texto completo (gratuito o de pago) 1146/annurev.immunol.19.1.131
AUTORES
/ AUTHORS: - Bach JF; Chatenoud L
INSTITUCIÓN
/ INSTITUTION: - INSERM U 25, Hopital Necker, 161 rue de
Sevres, Paris Cedex 15, 75743 France. bach@necker.fr
RESUMEN
/ SUMMARY: - Tolerance to beta cell autoantigens
represents a fragile equilibrium. Autoreactive T cells specific to these
autoantigens are present in most normal individuals but are kept under control
by a number of peripheral tolerance mechanisms, among which CD4(+) CD25(+)
CD62L(+) T cell-mediated regulation probably plays a central role. The
equilibrium may be disrupted by inappropriate activation of autoantigen-specific
T cells, notably following to local inflammation that enhances the expression
of the various molecules contributing to antigen recognition by T cells. Even
when T cell activation finally overrides regulation, stimulation of regulatory
cells by CD3 antibodies may reset the control of autoimmunity. Other procedures
may also lead to disease prevention. These procedures are essentially focused
on Th2 cytokines, whether used systemically or produced by Th2 cells after
specific stimulation by autoantigens. Protection can also be obtained by NK T
cell stimulation. Administration of beta cell antigens or CD3 antibodies is now
being tested in clinical trials in prediabetics and/or recently diagnosed
diabetes. N. Ref:: 153
----------------------------------------------------
[196]
TÍTULO / TITLE: - Early experience using
calcineurin-free protocol in recipients of high-risk cadaver renal transplants.
REVISTA
/ JOURNAL: - Transplant Proc 2002 Aug;34(5):1627-8.
AUTORES
/ AUTHORS: - El-Sabrout R; Delaney V; Butt F; Qadir M;
Rashid I; Hanson P; Butt K
INSTITUCIÓN
/ INSTITUTION: - Departments of Transplantation/Vascular
Surgery, New York Medical College, Valhalla, New York, USA.
----------------------------------------------------
[197]
TÍTULO / TITLE: - Reactivation of
replication of hepatitis B and C viruses after immunosuppressive therapy: an
unresolved issue.
REVISTA
/ JOURNAL: - Lancet Oncol 2002 Jun;3(6):333-40.
AUTORES
/ AUTHORS: - Vento S; Cainelli F; Longhi MS
INSTITUCIÓN
/ INSTITUTION: - Section of Infectious Diseases, Department
of Pathology, University of Verona, Borgo Trento Hospital, Verona, Italy. ventosandro@yahoo.it
RESUMEN
/ SUMMARY: - The liver is susceptible to the toxic
effects of many cytotoxic or immunosuppressive treatments. However, in carriers
of hepatitis B virus (HBV) and, less frequently, of hepatitis C virus, liver
damage due to reactivation of viral replication can occur after withdrawal of
immunosuppressive drugs. These reactivations, which are associated with
fulminant forms of hepatitis in up to 25% of cases, are observed both in
symptom-free chronic carriers of hepatitis B surface antigen and in patients
who have chronic hepatitis B or C and concurrent haematological tumours or solid
neoplasms or who have received transplants. HBV-related complications may cause
delays or modifications of therapy, and the chance of cure is reduced. In this
review, we analyse clinical, biochemical, and serological issues in
reactivation of viral replication and examine the role of immune reactions in
the pathogenesis and the possible toxicity of immunosuppressive drugs. We
emphasise the importance of identifying predictive markers of a clinically
relevant reactivation, review difficulties in drug prevention and treatment,
indicate studies that are needed to address the key clinical issues, and give
practical recommendations to practising physicians and oncologists. N. Ref:: 60
----------------------------------------------------
[198]
TÍTULO / TITLE: - Hepatitis B virus (HBV)
reactivation after cytotoxic or immunosuppressive therapy—pathogenesis and
management.
REVISTA
/ JOURNAL: - Rev Med Virol 2001 Sep-Oct;11(5):287-99.
●●
Enlace al texto completo (gratuito o de pago) 1002/rmv.322 [pii]
AUTORES
/ AUTHORS: - Xunrong L; Yan AW; Liang R; Lau GK
INSTITUCIÓN
/ INSTITUTION: - University Department of Medicine, Queen
Mary Hospital, 102 Pokfulum Road, Hong Kong SAR, China.
RESUMEN
/ SUMMARY: - In an endemic area for chronic hepatitis B
infection, reactivation of this virus is a serious cause of morbidity and
mortality in patients undergoing cytotoxic or immunosuppressive therapy.
Careful prospective serological testing has shown that hepatitis B virus
reactivation is a two-staged process. The initial stage occurs during intense
cytotoxic or immunosuppressive therapy and is characterised by enhanced viral
replication, as reflected by increases in the serum levels of hepatitis B virus
DNA, hepatitis B e antigen, hepatitis B virus DNA polymerase and infection of
naive hepatocytes with hepatitis B virus. The second stage is related to
restoration of immune function following withdrawal of cytotoxic or
immunosuppressive therapy, which causes rapid immune-mediated destruction of
infected hepatocytes. Clinically, this can lead to hepatitis, hepatic failure
and even death. The occurrence and severity of hepatitis B virus reactivation after
various cytotoxic or immunosuppressive therapy is unpredictable and treatment
has been disappointing, largely due to the late administration of therapy.
Recently, pre-emptive treatment of chronic hepatitis B patients undergoing
cytotoxic or immunosuppressive therapy, with potent nucleoside analogues has
shown some promising results. Further controlled studies are needed to define
the incidence and risk factors of hepatitis B reactivation so that pre-emptive
treatment with nucleoside analogues could be administered to those patients at
high risk of disease. N.
Ref:: 93
----------------------------------------------------
[199]
TÍTULO / TITLE: - Osteoporosis after
liver transplantation.
REVISTA
/ JOURNAL: - Liver Transpl 2003 Apr;9(4):321-30.
●●
Enlace al texto completo (gratuito o de pago) 1053/jlts.2003.50044
AUTORES
/ AUTHORS: - Compston JE
INSTITUCIÓN
/ INSTITUTION: - Department of Medicine, University of
Cambridge School of Clinical Medicine, United Kingdom. jec1001@cam.ac.uk
RESUMEN
/ SUMMARY: - Osteoporosis remains a serious potential
complication of liver transplantation, although its incidence may be
significantly reduced by the use of lower doses of glucocorticoids. Additional
factors likely to contribute to its pathogenesis include other
immunosuppressive agents, particularly cyclosporin A and FK506, vitamin D
insufficiency, secondary hyperparathyroidism, hypogonadism and pre-existing
bone disease. Bone density assessment and spinal X-rays should be performed
before transplantation to assess subsequent fracture risk and vitamin D and
gonadal status assessed. Measures should be taken to optimise bone health prior
to transplantation; in those with low bone mineral density and/or previous
fragility fracture, prophylaxis against bone loss after transplantation should
be considered. Although anti-fracture efficacy has not been established for any
agent there is evidence, mainly in patients undergoing other forms of solid
organ transplantation, that repeated infusions of pamidronate may be effective
in preventing bone loss. N.
Ref:: 81
----------------------------------------------------
[200]
TÍTULO / TITLE: - Management of internal
fistulas in Crohn’s disease.
REVISTA
/ JOURNAL: - Inflamm Bowel Dis 2002 Mar;8(2):106-11.
AUTORES
/ AUTHORS: - Levy C; Tremaine WJ
INSTITUCIÓN
/ INSTITUTION: - IBD Clinic, Division of Gastroenterology
and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, U.S.A.
RESUMEN
/ SUMMARY: - Internal fistulas occur in 5-10% of
patients with Crohn’s disease. The clinical presentation of each of the three
main types of internal fistulas—enteroenteric, enterovaginal, and enterovesical
fistulas—is important in determining the best management. Asymptomatic fistulas
usually require no treatment, but fistulas that cause severe or persistent
symptoms necessitate intervention. Previously regarded as a surgical condition
requiring resection, some internal fistulas are amenable to a more conservative
approach involving medical therapy, surgical repair, or both. So far, there
have not been any prospective studies designed specifically to assess the
efficacy of a medical treatment of internal fistulas, and information about treatment
results is gleaned from trials in which patients with internal fistulas have
been included and from retrospective reports. Drugs that have been reported to
close internal fistulas partially or completely include azathioprine,
6-mercaptopurine, mycophenolate mofetil, cyclosporine A, tacrolimus, and
infliximab. Reparative surgical techniques include transrectal and transvaginal
mucosal advancement flaps, cutaneous advancement flap, and anal stricturectomy
in combination with a rectal mucosal advancement sleeve. Prospective trials of
medical therapy and combination medical and surgical therapy for internal
fistulas are needed to provide evidence to support the use of these new
therapeutic approaches. N.
Ref:: 44
----------------------------------------------------