#08#
Revisiones-Clínica-Terapéutica
& Ensayos Clínicos *** Reviews-Clinical-Therapeutics & Clinical Trials
INMUNOSUPRESIÓN
*** IMMUNOSUPPRESSION
(Conceptos
/ Keywords: Immunosuppression; Immunosuppressive ag.; Transpl. immunol.; GVH;
Antirejection therapy; Lymphocyte depletion; Transpl. conditioning; etc).
Enero /
January 2001 --- Marzo / March 2004
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[1]
TÍTULO / TITLE: - Beta lactam monotherapy
versus beta lactam-aminoglycoside combination therapy for sepsis in
immunocompetent patients: systematic review and 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): <> 2004 Mar 20;328(7441):668. Epub 2004
Mar 2.
●●
Enlace al texto completo (gratuito o de pago) 1136/bmj.38028.520995.63
AUTORES
/ AUTHORS: - Paul M; Benuri-Silbiger I; Soares-Weiser
K; Leibovici L
INSTITUCIÓN
/ INSTITUTION: - Department of Medicine E and Infectious
Diseases Unit, Rabin Medical Centre, Beilinson Campus, Petah-Tikva 49100,
Israel. mica@zahav.net.il
RESUMEN
/ SUMMARY: - OBJECTIVE: To compare beta lactam
monotherapy with beta lactam-aminoglycoside combination therapy for severe
infections. DATA SOURCES: Medline, Embase, Lilacs, Cochrane Library, and
conference proceedings, to 2003; references of included studies; contact with
all authors. No restrictions, such as language, year of publication, or
publication status. STUDY SELECTION: All randomised trials of beta lactam
monotherapy compared with beta lactam-aminoglycoside combination therapy for patients
without neutropenia who fulfilled criteria for sepsis. DATA SELECTION: Two
reviewers independently applied selection criteria, performed quality
assessment, and extracted the data. The primary outcome assessed was all cause
fatality by intention to treat. Relative risks were pooled with the random
effect model (relative risk < 1 favours monotherapy). RESULTS: 64 trials
with 7586 patients were included. There was no difference in all cause fatality
(relative risk 0.90, 95% confidence interval 0.77 to 1.06). 12 studies compared
the same beta lactam (1.02, 0.76 to 1.38), and 31 studies compared different
beta lactams (0.85, 0.69 to 1.05). Clinical failure was more common with
combination treatment overall (0.87, 0.78 to 0.97) and among studies comparing different
beta lactams (0.76, 0.68 to 0.86). There was no advantage to combination
therapy among patients with Gram negative infections (1835 patients) or
Pseudomonas aeruginosa infections (426 patients). There was no difference in
the rate of development of resistance. Nephrotoxicity was significantly more
common with combination therapy (0.36, 0.28 to 0.47). Heterogeneity was not
significant for these comparisons. CONCLUSIONS: In the treatment of sepsis the
addition of an aminoglycoside to beta lactams should be discouraged. Fatality
remains unchanged, while the risk for adverse events is increased. N. Ref:: 26
----------------------------------------------------
[2]
TÍTULO / TITLE: - Immunopathogenesis and
immunotherapy in AIDS virus infections.
REVISTA
/ JOURNAL: - Nat Med 2003 Jul;9(7):861-6.
●●
Enlace al texto completo (gratuito o de pago) 1038/nm0703-861
AUTORES
/ AUTHORS: - Letvin NL; Walker BD
INSTITUCIÓN
/ INSTITUTION: - Division of Viral Pathogenesis, Beth
Israel Deaconess Medical Center, Massachusetts General Hospital, Harvard
Medical School, Boston, Massachusetts 02114, USA.
RESUMEN
/ SUMMARY: - The heterogeneity of HIV and the different
human leukocyte antigen (HLA) backgrounds of infected individuals have posed
challenges to understanding the pathogenesis of HIV infection. But continuing
advances in our knowledge of the role of immune responses in controlling HIV
viremia should help to define goals for immune-based therapies and vaccine
strategies against AIDS. N.
Ref:: 106
----------------------------------------------------
[3]
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
----------------------------------------------------
[4]
TÍTULO / TITLE: - Routes to transplant
tolerance versus rejection; the role of cytokines.
REVISTA
/ JOURNAL: - Immunity 2004 Feb;20(2):121-31.
AUTORES
/ AUTHORS: - Walsh PT; Strom TB; Turka LA
INSTITUCIÓN
/ INSTITUTION: - University of Pennsylvania, 700 Clinical
Research Building, 415 Curie Boulevard, Philadelphia, PA 19104, USA.
RESUMEN
/ SUMMARY: - The alloimmune response can be divided
into specific junctures where critical decisions between tolerance and immunity
are made which define the outcome of the transplant. At these “decision nodes”
various cytokines direct alloresponsive T cells to develop either a
proinflammatory response aimed at graft destruction or an immunoregulatory
response facilitating graft acceptance. This review will focus on the role of
these cytokines in influencing the progression of an alloimmune response
leading ultimately to either allograft survival or rejection. N. Ref:: 97
----------------------------------------------------
[5]
TÍTULO / TITLE: - Microchimerism: an
investigative frontier in autoimmunity and transplantation.
REVISTA
/ JOURNAL: - JAMA. Acceso gratuito al texto completo.
●●
Enlace a la Editora de la Revista http://jama.ama-assn.org/search.dtl
●●
Cita: JAMA: <> 2004 Mar 3;291(9):1127-31.
●●
Enlace al texto completo (gratuito o de pago) 1001/jama.291.9.1127
AUTORES
/ AUTHORS: - Adams KM; Nelson JL
INSTITUCIÓN
/ INSTITUTION: - Program in Human Immunogenetics, Clinical
Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA
98109-1024, USA.
RESUMEN
/ SUMMARY: - Recent studies indicate cells transfer
between fetus and mother during pregnancy and can persist in both decades
later. The presence within one individual of a small population of cells from
another genetically distinct individual is referred to as microchimerism.
Naturally acquired microchimerism has recently been investigated in autoimmune
diseases, including scleroderma, thyroiditis, primary biliary cirrhosis,
Sjogren syndrome, systemic lupus, dermatomyositis, and neonatal lupus. Iatrogenic
chimerism has been investigated in transplantation and following blood
transfusion. Considering findings of naturally acquired microchimerism along
with iatrogenic microchimerism suggests microchimerism can have detrimental
and/or beneficial effects in both settings. Recent identification of
tissue-specific microchimerism either from naturally acquired or iatrogenic
microchimerism (eg, cardiac myocytes) raises the possibility that
microchimerism can be a target of autoimmunity or alternatively contribute to
tissue repair. Advances in this new frontier of research with varied and
numerous implications for human health are summarized. N. Ref:: 26
----------------------------------------------------
[6]
TÍTULO / TITLE: - The allogeneic response
and tumor immunity.
REVISTA
/ JOURNAL: - Nat Med 2001 Jun;7(6):649-52.
●●
Enlace al texto completo (gratuito o de pago) 1038/89008
AUTORES
/ AUTHORS: - Fabre JW
INSTITUCIÓN
/ INSTITUTION: - Department of Clinical Sciences, Institute
of Liver Studies Guy’s, King’s and St Thomas’ School of Medicine, London, UK. john.fabre@kcl.ac.uk
RESUMEN
/ SUMMARY: - The strong allogeneic response to donor
MHC molecules in transplantation and the weak response to tumor antigens
represent two important and divergent but potentially interactive immune
responses. A patient’s response to allogeneic MHC molecules might promote an
effective T-cell response to self MHC-restricted tumor peptides and the
possibilities for this are discussed here. These allogeneic responses might
successfully be harnessed to promote the immune eradication of metastatic
cancer. N. Ref:: 45
----------------------------------------------------
[7]
TÍTULO / TITLE: - A review of activity
indices and efficacy endpoints for clinical trials of medical therapy in adults
with Crohn’s disease.
REVISTA
/ JOURNAL: - Gastroenterology 2002 Feb;122(2):512-30.
AUTORES
/ AUTHORS: - Sandborn WJ; Feagan BG; Hanauer SB; Lochs
H; Lofberg R; Modigliani R; Present DH; Rutgeerts P; Scholmerich J; Stange EF;
Sutherland LR
INSTITUCIÓN
/ INSTITUTION: - The Clinical Trials Task Force of the
International Organization of Inflammatory Bowel Disease. sandborn.william@mayo.edu N. Ref:: 115
----------------------------------------------------
[8]
TÍTULO / TITLE: - Skin cancers after
organ transplantation.
REVISTA
/ JOURNAL: - N Engl J Med. Acceso gratuito al texto
completo a partir de los 6 meses de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://content.nejm.org/
●●
Cita: New England J Medicine (NEJM): <> 2003 Apr 24;348(17):1681-91.
●●
Enlace al texto completo (gratuito o de pago) 1056/NEJMra022137
AUTORES
/ AUTHORS: - Euvrard S; Kanitakis J; Claudy A
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology, Edouard Herriot
Hospital, Lyons, France. sylvie.euvrard@numericable.fr N. Ref:: 100
----------------------------------------------------
[9]
TÍTULO / TITLE: - Haematopoietic cell
transplantation as immunotherapy.
REVISTA
/ JOURNAL: - Nature 2001 May 17;411(6835):385-9.
●●
Enlace al texto completo (gratuito o de pago) 1038/35077251
AUTORES
/ AUTHORS: - Appelbaum FR
INSTITUCIÓN
/ INSTITUTION: - Clinical Research Division, Fred
Hutchinson Cancer Research Center, 1100 Fairview Avenue North, D5-310, PO Box
19024, Seattle, Washington 98109-1024, USA.
RESUMEN
/ SUMMARY: - The graft-versus-tumour effect seen after
allogeneic (genetically different) haematopoietic cell transplantation for
human malignancies represents the clearest example of the power of the human
immune system to eradicate cancer. Recent advances in our understanding of the
immunobiology of stem-cell engraftment, tolerance and tumour eradication are
allowing clinicians to better harness this powerful effect. N. Ref:: 60
----------------------------------------------------
[10]
TÍTULO / TITLE: - Chronic graft-vs-host
disease.
REVISTA
/ JOURNAL: - JAMA. Acceso gratuito al texto completo.
●●
Enlace a la Editora de la Revista http://jama.ama-assn.org/search.dtl
●●
Cita: JAMA: <> 2003 Nov 19;290(19):2599-603.
●●
Enlace al texto completo (gratuito o de pago) 1001/jama.290.19.2599
AUTORES
/ AUTHORS: - Bhushan V; Collins RH Jr
INSTITUCIÓN
/ INSTITUTION: - Hematopoietic Cell Transplantation
Program, Department of Internal Medicine, University of Texas Southwestern
Medical Center, Dallas 75390-8852, USA.
N. Ref:: 26
----------------------------------------------------
[11]
TÍTULO / TITLE: - Interferon-gamma
reduces interleukin-4- and interleukin-13-augmented transforming growth
factor-beta2 production in human bronchial epithelial cells by targeting Smads.
REVISTA
/ JOURNAL: - Chest. Acceso gratuito al texto completo a
partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.chestjournal.org/
●●
Cita: Chest: <> 2003 Mar;123(3 Suppl):372S-3S.
AUTORES
/ AUTHORS: - Wen FQ; Liu XD; Terasaki Y; Fang QH;
Kobayashi T; Abe S; Rennard SI
INSTITUCIÓN
/ INSTITUTION: - Pulmonary and Critical Care Medicine
Section, University of Nebraska Medical Center, Omaha, NE 68198-5125, USA. N. Ref:: 0
----------------------------------------------------
[12]
TÍTULO / TITLE: - Ex vivo selection of
recipient-type alloantigen-specific CD4(+)CD25(+) immunoregulatory T cells for
the control of graft-versus-host disease after allogeneic hematopoietic
stem-cell transplantation.
REVISTA
/ JOURNAL: - Transplantation 2004 Jan 15;77(1
Suppl):S32-4.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000106470.07410.CA
AUTORES
/ AUTHORS: - Trenado A; Fisson S; Braunberger E;
Klatzmann D; Salomon BL; Cohen JL
INSTITUCIÓN
/ INSTITUTION: - Biologie et Therapeutique des Pathologies
Immunitaires, Hopital Pitie-Salpetriere, Paris, France.
RESUMEN
/ SUMMARY: - Allogeneic hematopoietic stem-cell
transplantation (HSCT) is the treatment of choice for many malignant and
nonmalignant hematologic disorders. Donor T cells present in the hematopoietic
stem-cell transplant improve engraftment and immune reconstitution and
contribute to the graft-versus-leukemia effect, but are also responsible for
the life-threatening graft-versus-host disease (GVHD). CD4(+)CD25(+)
immunoregulatory T cells, which play a pivotal role in preventing
organ-specific diseases, can also modulate GVHD if administered in equal
numbers of T cells at the time of grafting. In this article, the authors
describe a procedure of ex vivo selection and expansion of regulatory T cells
specific for recipient-type alloantigens. These expanded regulatory T cells
controlled GVHD. Their therapeutic use in HSCT should allow specific
suppression of the activation of donor alloreactive T cells involved in GVHD
while preserving the beneficial effects of other T cells. N. Ref:: 27
----------------------------------------------------
[13]
TÍTULO / TITLE: - Hemochromatosis gene
modifies course of hepatitis C viral infection.
REVISTA
/ JOURNAL: - Gastroenterology 2003 May;124(5):1509-23.
AUTORES
/ AUTHORS: - Pietrangelo A
INSTITUCIÓN
/ INSTITUTION: - Department of Internal Medicine, Centre
for Hemochromatosis and Metabolic Liver Diseases, University of Modena and
Reggio Emilia, Modeno, Italy. antonello@unimore.it N. Ref:: 161
----------------------------------------------------
[14]
- 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
----------------------------------------------------
[15]
TÍTULO / TITLE: - Regulating the immune
response to transplants. a role for CD4+ regulatory cells?
REVISTA
/ JOURNAL: - Immunity 2001 Apr;14(4):399-406.
AUTORES
/ AUTHORS: - Waldmann H; Cobbold S
INSTITUCIÓN
/ INSTITUTION: - Sir William Dunn School of Pathology,
University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom. herman.waldmann@path.ox.ac.uk N. Ref:: 50
----------------------------------------------------
[16]
TÍTULO / TITLE: - Dendritic cells in
transplantation—friend or foe?
REVISTA
/ JOURNAL: - Immunity 2001 Apr;14(4):357-68.
AUTORES
/ AUTHORS: - Lechler R; Ng WF; Steinman RM
INSTITUCIÓN
/ INSTITUTION: - Department of Immunology, Division of
Medicine, Hammersmith Hospital, Imperial College School of Medicine, Du Cane
Road, London W12 ONN, United Kingdom. r.lechler@ic.ac.uk N. Ref:: 80
----------------------------------------------------
[17]
TÍTULO / TITLE: - Clinical practice
guidelines for managing dyslipidemias in kidney transplant patients: a report
from the Managing Dyslipidemias in Chronic Kidney Disease Work Group of the
National Kidney Foundation Kidney Disease Outcomes Quality Initiative.
REVISTA
/ JOURNAL: - Am J Transplant 2004;4 Suppl 7:13-53.
●●
Enlace al texto completo (gratuito o de pago) 1111/j.1600-6135.2004.0355.x
AUTORES
/ AUTHORS: - Kasiske B; Cosio FG; Beto J; Bolton K;
Chavers BM; Grimm R Jr; Levin A; Masri B; Parekh R; Wanner C; Wheeler DC;
Wilson PW
RESUMEN
/ SUMMARY: - The incidence of cardiovascular disease
(CVD) is very high in patients with chronic kidney (CKD) disease and in kidney
transplant recipients. Indeed, available evidence for these patients suggests
that the 10-year cumulative risk of coronary heart disease is at least 20%, or
roughly equivalent to the risk seen in patients with previous CVD. Recently,
the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative
(K/DOQI) published guidelines for the diagnosis and treatment of dyslipidemias
in patients with CKD, including transplant patients. It was the conclusion of
this Work Group that the National Cholesterol Education Program Guidelines are
generally applicable to patients with CKD, but that there are significant
differences in the approach and treatment of dyslipidemias in patients with CKD
compared with the general population. In the present document we present the
guidelines generated by this workgroup as they apply to kidney transplant
recipients. Evidence from the general population indicates that treatment of
dyslipidemias reduces CVD, and evidence in kidney transplant patients suggests
that judicious treatment can be safe and effective in improving dyslipidemias.
Dyslipidemias are very common in CKD and in transplant patients. However, until
recently there have been no adequately powered, randomized, controlled trials
examining the effects of dyslipidemia treatment on CVD in patients with CKD.
Since completion of the K/DOQI guidelines on dyslipidemia in CKD, the results
of the Assessment of Lescol in Renal Transplantation (ALERT) Study have been
presented and published. Based on information from randomized trials conducted
in the general population and the single study conducted in kidney transplant
patients, these guidelines, which are a modified version of the K/DOQI dyslipidemia
guidelines, were developed to aid clinicians in the management of dyslipidemias
in kidney transplant patients. These guidelines are divided into four sections.
The first section (Introduction) provides the rationale for the guidelines, and
describes the target population, scope, intended users, and methods. The second
section presents guidelines on the assessment of dyslipidemias (guidelines
1-3), while the third section offers guidelines for the treatment of
dyslipidemias (guidelines 4-5). The key guideline statements are supported
mainly by data from studies in the general population, but there is an urgent
need for additional studies in CKD and in transplant patients. Therefore, the
last section outlines recommendations for research.
----------------------------------------------------
[18]
TÍTULO / TITLE: - Disease modifying
therapies in multiple sclerosis: report of the Therapeutics and Technology
Assessment Subcommittee of the American Academy of Neurology and the MS Council
for Clinical Practice Guidelines.
REVISTA
/ JOURNAL: - Neurology 2002 Jan 22;58(2):169-78.
AUTORES
/ AUTHORS: - Goodin DS; Frohman EM; Garmany GP Jr;
Halper J; Likosky WH; Lublin FD; Silberberg DH; Stuart WH; van den Noort S
----------------------------------------------------
[19]
TÍTULO / TITLE: - Nystatin prophylaxis
and treatment in severely immunodepressed patients.
REVISTA
/ JOURNAL: - Cochrane Database Syst Rev
2002;(4):CD002033.
AUTORES
/ AUTHORS: - Gotzsche PC; Johansen HK
INSTITUCIÓN
/ INSTITUTION: - The Nordic Cochrane Centre,
Rigshospitalet, Dept. 7112, Blegdamsvej 9, Copenhagen O, Denmark, 2100. p.c.gotzsche@cochrane.dk
RESUMEN
/ SUMMARY: - BACKGROUND: Nystatin is sometimes used
prophylactically in patients with severe immunodeficiency or in the treatment
of fungal infection in such patients, although the effect seems to be
equivocal. OBJECTIVES: To study whether nystatin decreases morbidity and
mortality when given prophylactically or therapeutically to patients with
severe immunodeficiency. SEARCH STRATEGY: MEDLINE and The Cochrane Library
using a comprehensive search strategy, date of last search November 2001.
Contacted industry and scanned reference lists. SELECTION CRITERIA: Randomised
trials comparing nystatin with placebo, an untreated control group, fluconazole
or amphotericin B. DATA COLLECTION AND ANALYSIS: Data on mortality, invasive
fungal infection and colonisation were extracted by both authors independently.
A random effects model was used unless p>0.10 for the test of heterogeneity.
MAIN RESULTS: We included 12 trials (1,464 patients). The drugs were given
prophylactically in ten trials and as treatment in two. Seven trials were in
acute leukaemia, two in cancer, one in liver transplant patients, one in
critically ill surgical and trauma patients, and one in AIDS patients. Nystatin
had been compared with placebo in three trials and with fluconazole in nine;
the dose varied from 1.5 MIE to 72 MIE daily. The effect of nystatin was
similar to that of placebo on fungal colonisation (relative risk 0.85, 95%
confidence interval 0.65 to 1.13). There was no statistically significant
difference between fluconazole and nystatin on mortality (relative risk 0.76,
0.49 to 1.18) whereas fluconazole was more effective in preventing invasive
fungal infection (relative risk 0.37, 0.15 to 0.91) and colonisation (relative
risk 0.49, 0.34 to 0.70). The results were very similar if the three studies
which were not performed in cancer patients were excluded. REVIEWER’S CONCLUSIONS:
Nystatin cannot be recommended for prophylaxis or treatment of Candida
infections in immunodepressed patients.
N. Ref:: 22
----------------------------------------------------
[20]
TÍTULO / TITLE: - Immune tolerance after
long-term enzyme-replacement therapy among patients who have
mucopolysaccharidosis I.
REVISTA
/ JOURNAL: - Lancet 2003 May 10;361(9369):1608-13.
AUTORES
/ AUTHORS: - Kakavanos R; Turner CT; Hopwood JJ; Kakkis
ED; Brooks DA
INSTITUCIÓN
/ INSTITUTION: - Lysosomal Diseases Research Unit,
Department of Chemical Pathology, Women’s and Children’s Hospital, North
Adelaide, South Australia, Australia
RESUMEN
/ SUMMARY: - BACKGROUND: Enzyme-replacement therapy has
been assessed as a treatment for patients who have mucopolysaccharidosis I
(alpha-L-iduronidase deficiency). We aimed to investigate the humoral immune
response to recombinant human alpha-L-iduronidase among these patients.
METHODS: We characterised the antibody titres and specific linear sequence
epitope reactivity of serum antibodies to alpha-L-iduronidase for ten patients
with mucopolysaccharidosis I, at the start of treatment and after 6, 12, 26,
52, and 104 weeks. We compared the values for patients’ samples with those for
samples from normal human controls. FINDINGS: Before enzyme-replacement
therapy, all patients had low serum antibody titres to recombinant human
alpha-L-iduronidase that were within the control range. Five of the ten
patients produced higher-than-normal titres of antibody to the replacement
protein during the treatment course (serum antibody titres 130000-500000 and
high-affinity epitope reactivity). However, by week 26, antibody reactivity was
reduced, and by week 104 all patients had low antibody titres and only
low-affinity epitope reactivity. Patients who had mucopolysaccharidosis I with
antibody titres within the normal range at 6-12 weeks did not subsequently
develop immune responses. INTERPRETATION: After 2 years of treatment, patients
who initially had an immune reaction developed immune tolerance to
alpha-L-iduronidase. This finding has positive implications for long-term
enzyme-replacement therapy in patients who have mucopolysaccharidosis I. N. Ref:: 32
----------------------------------------------------
[21]
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.
----------------------------------------------------
[22]
TÍTULO / TITLE: - Regulatory T cells in
transplantation tolerance.
REVISTA
/ JOURNAL: - Nat Rev Immunol 2003 Mar;3(3):199-210.
●●
Enlace al texto completo (gratuito o de pago) 1038/nri1027
AUTORES
/ AUTHORS: - Wood KJ; Sakaguchi S
INSTITUCIÓN
/ INSTITUTION: - Nuffield Department of Surgery, University
of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK. kathryn.wood@nds.ox.ac.uk
RESUMEN
/ SUMMARY: - The identification and characterization of
regulatory T (T(Reg)) cells that can control immune responsiveness to alloantigens
have opened up exciting opportunities for new therapies in transplantation.
After exposure to alloantigens in vivo, alloantigen-specific immunoregulatory
activity is enriched in a population of CD4+ T cells that express high levels
of CD25. In vivo, common mechanisms seem to underpin the activity of CD4+CD25+
T(Reg) cells in both naive and manipulated hosts. However, the origin,
allorecognition properties and molecular basis for the suppressive activity of
CD4+CD25+ T(Reg) cells, as well as their relationship to other populations of
regulatory cells that exist after transplantation, remain a matter of
debate. N. Ref:: 138
----------------------------------------------------
[23]
TÍTULO / TITLE: - Interleukin 2 receptor
antagonists for renal transplant recipients: a meta-analysis of randomized
trials.
REVISTA
/ JOURNAL: - Transplantation 2004 Jan 27;77(2):166-76.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000109643.32659.C4
AUTORES
/ AUTHORS: - Webster AC; Playford EG; Higgins G;
Chapman JR; Craig JC
INSTITUCIÓN
/ INSTITUTION: - Cochrane Renal Group, Centre for Kidney
Research, Children’s Hospital at Westmead, Westmead, NSW, Australia.
RESUMEN
/ SUMMARY: - BACKGROUND: Interleukin 2 receptor
antagonists (IL-2Ra) are increasingly used to treat renal transplant
recipients. This study aims to systematically identify and summarize the
effects of using IL-2Ra as induction immunosuppression, as an addition to standard
therapy, or as an alternative to other antibody therapy. METHODS: Databases,
reference lists, and abstracts of conference proceedings were searched
extensively to identify relevant randomized controlled trials in all languages.
Data were synthesized using the random effects model. Results are expressed as
relative risk (RR), with 95% confidence intervals (CI). RESULTS: A total of 117
reports from 38 trials involving 4,893 participants were included. When IL-2Ra
were compared with placebo (17 trials; 2,786 patients), graft loss was not
significantly different at 1 year (14 trials: RR 0.84; CI 0.64-1.10) or 3 years
(4 trials: RR 1.08; CI 0.71-1.64). Acute rejection was significantly reduced at
6 months (12 trials: RR 0.66; CI 0.59-0.74) and at 1 year (10 trials: RR 0.67;
CI 0.60-0.75). At 1 year, cytomegalovirus infection (7 trials: RR 0.82; CI
0.65-1.03) and malignancy (9 trials: RR 0.67; CI 0.33-1.36) were not
significantly different. When IL-2Ra were compared with other antibody therapy,
no significant differences in treatment effects were demonstrated, but IL-2Ra
had significantly fewer side effects. CONCLUSIONS: Given a 40% risk of
rejection, seven patients would need treatment with IL-2Ra in addition to
standard therapy, to prevent one patient from undergoing rejection, with no
definite improvement in graft or patient survival. There is no apparent
difference between basiliximab and daclizumab.
----------------------------------------------------
[24]
TÍTULO / TITLE: - Tolerance and
autoimmunity.
REVISTA
/ JOURNAL: - N Engl J Med. Acceso gratuito al texto
completo a partir de los 6 meses de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://content.nejm.org/
●●
Cita: New England J Medicine (NEJM): <> 2001 Mar 1;344(9):655-64.
AUTORES
/ AUTHORS: - Kamradt T; Mitchison NA
INSTITUCIÓN
/ INSTITUTION: - Deutsches Rheumaforschungszentrum Berlin
and Universitatsklinikum Charite, Medizinische Klinik mit Schwerpunkt
Rheumatologie and Klinische Immunologie, Germany. kamradt@drfz.de N. Ref:: 151
----------------------------------------------------
[25]
TÍTULO / TITLE: - Progress in the
treatment of rheumatoid arthritis.
REVISTA
/ JOURNAL: - JAMA. Acceso gratuito al texto completo.
●●
Enlace a la Editora de la Revista http://jama.ama-assn.org/search.dtl
●●
Cita: JAMA: <> 2001 Dec 12;286(22):2787-90.
AUTORES
/ AUTHORS: - Pisetsky DS; St Clair EW
INSTITUCIÓN
/ INSTITUTION: - Division of Rheumatology, Allergy, and
Clinical Immunology, Duke University Medical Center, 1516 Durham Veterans
Affairs Medical Center, Box 151G, Durham, NC 27710, USA. dpiset@acpub.duke.edu N. Ref:: 27
----------------------------------------------------
[26]
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
----------------------------------------------------
[27]
TÍTULO / TITLE: - Strategies to improve
long-term outcomes after renal transplantation.
REVISTA
/ JOURNAL: - N Engl J Med. Acceso gratuito al texto
completo a partir de los 6 meses de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://content.nejm.org/
●●
Cita: New England J Medicine (NEJM): <> 2002 Feb 21;346(8):580-90.
●●
Enlace al texto completo (gratuito o de pago) 1056/NEJMra011295
AUTORES
/ AUTHORS: - Pascual M; Theruvath T; Kawai T;
Tolkoff-Rubin N; Cosimi AB
INSTITUCIÓN
/ INSTITUTION: - Renal Unit, Department of Medicine,
Massachusetts General Hospital, Boston, MA 02114, USA. mpascual@partners.org N. Ref:: 99
----------------------------------------------------
[28]
TÍTULO / TITLE: - Tolerogenic dendritic
cells induced by vitamin D receptor ligands enhance regulatory T cells
inhibiting allograft rejection and autoimmune diseases.
REVISTA
/ JOURNAL: - J Cell Biochem 2003 Feb 1;88(2):227-33.
●●
Enlace al texto completo (gratuito o de pago) 1002/jcb.10340
AUTORES
/ AUTHORS: - Adorini L; Penna G; Giarratana N;
Uskokovic M
INSTITUCIÓN
/ INSTITUTION: - BioXell, SpA, 20132 Milano, Italy. luciano.adorini@bioxell.com
RESUMEN
/ SUMMARY: - Dendritic cells (DCs) not only induce but
also modulate T cell activation. 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)]
induces DCs with a tolerogenic phenotype, characterized by decreased expression
of CD40, CD80, and CD86 costimulatory molecules, low IL-12 and enhanced IL-10
secretion. We have found that a short treatment with 1,25(OH)(2)D(3) induces
tolerance to fully mismatched mouse islet allografts that is stable to
challenge with donor-type spleen cells and allows acceptance of donor-type
vascularized heart grafts. This effect is enhanced by co-administration of
mycophenolate mofetil (MMF), a selective inhibitor of T and B cell
proliferation that has also effects similar to 1,25(OH)(2)D(3) on DCs. Graft
acceptance is associated with an increased percentage of CD4(+)CD25(+)
regulatory cells in the spleen and in the draining lymph node that can protect
100% of syngeneic recipients from islet allograft rejection. CD4(+)CD25(+)
cells, able to inhibit the T cell response to a pancreatic autoantigen and to
significantly delay disease transfer by pathogenic CD4(+)CD25(-) cells, are
also induced by treatment of adult nonobese diabetic (NOD) mice with
1,25-dihydroxy-16,23Z-diene-26,27-hexafluoro-19-nor vitamin D(3) (BXL-698).
This treatment arrests progression of insulitis and Th1 cell infiltration, and
inhibits diabetes development at non-hypercalcemic doses. The enhancement of
CD4(+)CD25(+) regulatory T cells, able to mediate transplantation tolerance and
to arrest type 1 diabetes development by a short oral treatment with VDR
ligands, suggests possible clinical applications of this approach. N. Ref:: 41
----------------------------------------------------
[29]
TÍTULO / TITLE: - T cell death and
transplantation tolerance.
REVISTA
/ JOURNAL: - Immunity 2001 Apr;14(4):407-16.
AUTORES
/ AUTHORS: - Li XC; Strom TB; Turka LA; Wells AD
INSTITUCIÓN
/ INSTITUTION: - Department of Medicine, Beth Israel
Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA. N. Ref:: 50
----------------------------------------------------
[30]
TÍTULO / TITLE: - Pathways for
self-tolerance and the treatment of autoimmune diseases.
REVISTA
/ JOURNAL: - Lancet 2001 Jun 30;357(9274):2115-21.
AUTORES
/ AUTHORS: - Goodnow CC
INSTITUCIÓN
/ INSTITUTION: - Australian Cancer Research Foundation,
Genetics Laboratory, Medical Genome Centre, John Curtin School of Medical
Research, Australian National University, Canberra, Australia.
RESUMEN / SUMMARY: - Antigen delivers both immunogenic and tolerogenic signals to lymphocytes. The outcome of antigen exposure represents a complex integration of the timing of antigen binding with signals from many other immunogenic and tolerogenic costimulatory pathways. A road map of these signalling pathways is only beginning to be char