#07#
Revisiones-Clínica-Complicaciones
*** Reviews-Clinical-Complications
AGENTES
INMUNOSUPRESORES *** IMMUNOSUPPRESSIVE COMPOUNDS
(Conceptos
/ Keywords: Immunosuppressive comp; Muromonab-cd3; Sirolimus; Tacrolimus;
Cyclosporine; Mycophenolic acid; Antilymphocyte serum; Immunosuppressive comp.
used in oncology, etc).
Enero /
January 2001 --- Marzo / March 2004
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[1]
TÍTULO / TITLE: - Interleukin-2 receptor
monoclonal antibodies in renal transplantation: meta-analysis of randomised
trials.
REVISTA
/ JOURNAL: - British Medical J (BMJ). Acceso gratuito
al texto completo.
●●
Enlace a la Editora de la Revista http://bmj.com/search.dtl
●●
Cita: British Medical J. (BMJ): <> 2003 Apr 12;326(7393):789.
●●
Enlace al texto completo (gratuito o de pago) 1136/bmj.326.7393.789
AUTORES
/ AUTHORS: - Adu D; Cockwell P; Ives NJ; Shaw J;
Wheatley K
INSTITUCIÓN
/ INSTITUTION: - Department of Nephrology, Queen Elizabeth
Hospital, Birmingham, B15 2TH. dwomoa.adu@uhb.nhs.uk
RESUMEN
/ SUMMARY: - OBJECTIVE: To study the effect of
interleukin-2 receptor monoclonal antibodies on acute rejection episodes, graft
loss, deaths, and rate of infection and malignancy in patients with renal
transplants. DESIGN: Meta-analysis of published data. DATA SOURCES: Medline,
Embase, and Cochrane library for years 1996-2003 plus search of medical
editors’ trial amnesty and contact with manufacturers of the antibodies.
SELECTION OF STUDIES: Randomised controlled trials comparing interleukin-2
receptor antibodies with placebo or no additional treatment in patients with
renal transplants receiving ciclosporin based immunosuppression. RESULTS: Eight
randomised controlled trials involving 1871 patients met the selection criteria
(although only 1858 patients were analysed). Interleukin-2 receptor antibodies
significantly reduced the risk of acute rejection (odds ratio 0.51, 95%
confidence interval 0.42 to 0.63). There were no significant differences in the
rate of graft loss (0.78, 0.58 to 1.04), mortality (0.75, 0.46 to 1.23),
overall incidence of infections (0.97, 0.77 to 1.24), incidence of
cytomegalovirus infections (0.81, 0.62 to 1.04), or risk of malignancies at one
year (0.82, 0.39 to 1.70). The different antibodies had a similar sized effect
on acute rejection (test for heterogeneity P=0.7): anti-Tac (0.37, 0.16 to
0.89), BT563 (0.37, 0.1 to 1.38), basiliximab (0.56, 0.44 to 0.72), and
daclizumab (0.46, 0.32 to 0.67). The reduction in acute rejections was similar
for all ciclosporin based immunosuppression regimens (test for heterogeneity
P=1.0). CONCLUSIONS: Adding interleukin-2 receptor antibodies to ciclosporin
based immunosuppression reduces episodes of acute rejection at six months by
49%. There is no evidence of an increased risk of infective complications.
Longer follow up studies are needed to confirm whether interleukin-2 receptor
antibodies improve long term graft and patient survival.
----------------------------------------------------
[2]
TÍTULO / TITLE: - 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.
----------------------------------------------------
[3]
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.
----------------------------------------------------
[4]
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
----------------------------------------------------
[5]
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.
----------------------------------------------------
[6]
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
----------------------------------------------------
[7]
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.
----------------------------------------------------
[8]
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
----------------------------------------------------
[9]
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
----------------------------------------------------
[10]
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
----------------------------------------------------
[11]
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
----------------------------------------------------
[12]
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.
----------------------------------------------------
[13]
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
----------------------------------------------------
[14]
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
----------------------------------------------------
[15]
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
----------------------------------------------------
[16]
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
----------------------------------------------------
[17]
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
----------------------------------------------------
[18]
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
----------------------------------------------------
[19]
TÍTULO / TITLE: - Is there still a role
for cyclosporine in the treatment of inflammatory bowel disease? Pro argument.
REVISTA
/ JOURNAL: - Inflamm Bowel Dis 2003 May;9(3):194-7;
discussion 202-4.
AUTORES
/ AUTHORS: - Kornbluth A
INSTITUCIÓN
/ INSTITUTION: - The Mount Sinai Medical Center, New York,
New York, USA. akornbluth@aol.com N. Ref:: 32
----------------------------------------------------
[20]
TÍTULO / TITLE: - Is there still a role
for cyclosporine in the treatment of inflammatory bowel disease? Con argument.
REVISTA
/ JOURNAL: - Inflamm Bowel Dis 2003 May;9(3):198-201;
discussion 202-4.
AUTORES
/ AUTHORS: - Fellermann K; Luhmann D; Stange EF
INSTITUCIÓN
/ INSTITUTION: - Department of Internal Medicine I, Robert-Bosch-Krankenhaus,
Stuttgart, Germany. klaus.fellermann@rbk.de N. Ref:: 21
----------------------------------------------------
[21]
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
----------------------------------------------------
[22]
TÍTULO / TITLE: - European best practice
guidelines for renal transplantation. Section IV: Long-term management of the
transplant recipient. IV.3.1 Long-term immunosuppression. Late steroid or
cyclosporine withdrawal.
REVISTA
/ JOURNAL: - Nephrol Dial Transplant. Acceso gratuito
al texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://ndt.oupjournals.org/
●●
Cita: Nephrology Dialysis Transplantation: <> 2002;17 Suppl 4:19-20.
RESUMEN
/ SUMMARY: - GUIDELINES: A. In order to reduce or avoid
long-term serious adverse effects of corticosteroids, such as bone fractures,
diabetes mellitus, arterial hypertension, osteoporosis and eye complications,
steroid withdrawal should be considered. B. Steroid withdrawal is safe only in
a proportion of graft recipients and is recommended only in low-risk patients.
The efficacy of the remaining immunosuppression should be considered. C. After
steroid withdrawal, graft function has to be monitored very carefully because
of the risk of a delayed but continuous loss of function due to chronic graft
dysfunction. In the case of functional deterioration or dysfunction, steroids
should be re-administered. D. Cyclosporine withdrawal might be considered in
order to ameliorate nephrotoxicity, arterial hypertension, lipid disorders and
hypertrichosis. This can be carried out with no significant long-term risk of
progressive graft loss. The efficacy of the remaining immunosuppression should
be considered. After cyclosporine withdrawal, careful monitoring for acute
rejection is recommended.
----------------------------------------------------
[23]
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
----------------------------------------------------
[24]
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
----------------------------------------------------
[25]
TÍTULO / TITLE: - Immunosuppression and
transplant vascular disease: benefits and adverse effects.
REVISTA
/ JOURNAL: - Pharmacol Ther 2003 Nov;100(2):141-56.
AUTORES
/ AUTHORS: - Moien-Afshari F; McManus BM; Laher I
INSTITUCIÓN
/ INSTITUTION: - Department of Pharmacology and
Therapeutics, Faculty of Medicine, University of British Columbia, 2176 Health
Sciences Mall, Vancouver, BC Canada V6T 1Z3.
RESUMEN
/ SUMMARY: - Cardiac allograft vasculopathy (CAV)
occurs within 5 years of transplantation surgery and represents the main cause
of death in long-term heart transplant survivors. The detailed pathogenesis of
CAV is unknown, but there are strong indications that immunologic mechanisms,
which are regulated by nonimmunologic factors, are the major cause of this
phenomenon. Cyclosporine A (CsA) is a frequently used immunosuppressive agent
in transplant medicine to prevent rejection. The mechanism of action of CsA
involves initial binding to cyclophilin to form a complex that then inhibits
calcineurin (CN), leading to reduced interleukin (IL)-2 production as part of
the signal transduction pathway for the activation of B-lymphocytes and
T-lymphocytes. Based on this proposed mechanism, it was expected that CsA
should be an effective strategy in attenuating the host immune response against
transplanted allograft tissue; however, CsA has not changed the outcome of CAV.
Several mechanisms have been suggested for the ineffectiveness of CsA in
long-term prevention of CAV. For example, routine therapeutic doses of CsA may
block CN incompletely (50%), whereas complete blockade requires doses that are
not clinically tolerable. Another explanation is the possible activation of
T-cell receptors directly (CN independent) by the immune response, which
induces protein kinase C theta (PKCtheta) and leads to IL-2 production and
immune rejection. Moreover, there may be a role for nonimmunologic mechanisms,
such as complement, which cannot be controlled by CsA, or CsA may cause
hypercholesterolemia or induce overexpression of transforming growth
factor-beta (TGF-beta). This review also compares the effect of CsA with other
immunosuppressants in allograft artery preservation and their clinical
efficacy. N. Ref:: 192
----------------------------------------------------
[26]
- 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
----------------------------------------------------
[27]
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
----------------------------------------------------
[28]
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
----------------------------------------------------
[29]
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
----------------------------------------------------
[30]
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
----------------------------------------------------
[31]
TÍTULO / TITLE: - Effectiveness of
sirolimus-eluting stent implantation for recurrent in-stent restenosis after
brachytherapy.
REVISTA
/ JOURNAL: - Am J Cardiol 2003 Jul 15;92(2):200-3.
AUTORES
/ AUTHORS: - Saia F; Lemos PA; Sianos G; Degertekin M;
Lee CH; Arampatzis CA; Hoye A; Tanabe K; Regar E; van der Giessen WJ; Smits PC;
de Feyter P; Ligthart J; van Domburg RT; Serruys PW
INSTITUCIÓN
/ INSTITUTION: - Erasmus MC, Thoraxcenter, Dr
Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. N. Ref:: 13
----------------------------------------------------
[32]
- 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
----------------------------------------------------
[33]
TÍTULO / TITLE: - Current
immunosuppressive agents: efficacy, side effects, and utilization.
REVISTA
/ JOURNAL: - Pediatr Clin North Am 2003
Dec;50(6):1283-300.
AUTORES
/ AUTHORS: - Smith JM; Nemeth TL; McDonald RA
INSTITUCIÓN
/ INSTITUTION: - Division of Nephrology, Children’s
Hospital and Regional Medical Center, 4800 Sand Point Way, NE 5G-1, Seattle, WA
98105-0371, USA. jodi.smith@seattlechildrens.org
RESUMEN
/ SUMMARY: - Advances in immunosuppressive therapy over
the past decade have led to dramatic improvements in graft survival. With the
development of new agents, the focus of the transplant community is to
establish regimens that maintain excellent graft survival rates but with fewer
toxicities including infection, nephrotoxicity, malignancy, and cosmetic
effects. Examples include the use of steroid-free protocols and calcineurin
avoidance regimens, which are currently being studied by NAPRTCS. The ultimate
goal of transplant immunosuppressive therapy is the induction of tolerance. As
we learn more about immune function from basic and clinical research, tolerance
to allografts seems a more reachable goal.
N. Ref:: 89
----------------------------------------------------
[34]
TÍTULO / TITLE: - European best practice
guidelines for renal transplantation. Section IV: Long-term management of the
transplant recipient. IV.2.1 Differential diagnosis of chronic graft
dysfunction.
REVISTA
/ JOURNAL: - Nephrol Dial Transplant. Acceso gratuito
al texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://ndt.oupjournals.org/
●●
Cita: Nephrology Dialysis Transplantation: <> 2002;17 Suppl 4:4-8.
RESUMEN
/ SUMMARY: - GUIDELINES: A. Any significant
deterioration in graft function should be investigated using the appropriate
diagnostic tools and, if possible, therapeutic interventions should be
initiated. The usual causes of a decline in glomerular filtration rate after
the first year include transplant-specific causes such as chronic allograft
nephropathy, acute rejection episodes, chronic calcineurin inhibitor
nephrotoxicity, transplant renal artery stenosis and ureteric obstruction, as
well as immunodeficiency-related causes and non-transplant-related causes, such
as recurrent or de novo renal diseases and bacterial infections. B. Any new
onset and persistent proteinuria of >0.5 g/24 h should be investigated and
therapeutic interventions should be initiated. The usual causes include chronic
allograft nephropathy and transplant glomerulopathy, and recurrent or de novo
glomerulonephritis.
----------------------------------------------------
[35]
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
----------------------------------------------------
[36]
- 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
----------------------------------------------------
[37]
TÍTULO / TITLE: - European best practice
guidelines for renal transplantation. Section IV: Long-term management of the
transplant recipient. IV.10. Pregnancy in renal transplant recipients.
REVISTA
/ JOURNAL: - Nephrol Dial Transplant. Acceso gratuito
al texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://ndt.oupjournals.org/
●●
Cita: Nephrology Dialysis Transplantation: <> 2002;17 Suppl 4:50-5.
RESUMEN
/ SUMMARY: - GUIDELINES: A. Renal transplantation
restores fertility, and successful pregnancies have been reported in renal
transplant women. In women with normal graft function, pregnancy usually has no
adverse effect on graft function and survival. Therefore, women of childbearing
age who consider pregnancy should receive complete information and support from
the transplant team. B. Pregnancy could be considered safe about 2 years after
transplantation in women with good renal function, without proteinuria, without
arterial hypertension, with no evidence of ongoing rejection and with normal
allograft ultrasound. C. Pregnancy after transplantation should be considered a
high-risk pregnancy and should be monitored by both an obstetrician and the
transplant physician. Pregnancy should be diagnosed as early as possible. The
principal risks are infection, proteinuria, anaemia, arterial hypertension and
acute rejection for the mother, and prematurity and low birth weight for the
foetus. D. Pregnant women and transplanted patients are at increased risk of
infections, especially bacterial urinary tract infections and acute
pyelonephritis of the graft. Urine cultures should be performed monthly and all
asymptomatic infections should be treated. Monitoring of viral infections is
also recommended. (Evidence level B) E. Acute rejection episodes are uncommon
but may occur after delivery. Therefore, immunosuppression should be
re-adjusted immediately after delivery. F. Because pre-eclampsia develops in
30% of pregnant patients, especially those with prior arterial transplant hypertension,
blood pressure, renal function, proteinuria and weight should be monitored
every 2-4 weeks, with more attention during the third trimester.
Anti-hypertensive agents should be changed to those tolerated during pregnancy.
ACE inhibitors and angiotensin II receptor antagonists are absolutely
contra-indicated. G. Immunosuppressive therapy based on cyclosporine or
tacrolimus with or without steroids and azathioprine may be continued in renal
transplant women during pregnancy. Other drugs, such as mycophenolate mofetil
and sirolimus, are not recommended based on current information available.
Because of drug transfer into maternal milk, breastfeeding is not recommended.
H. Vaginal delivery is recommended, but caesarean section is required in at
least 50% of cases. Delivery should occur in a specialized centre. In the
puerperium, renal function, proteinuria, blood pressure,
cyclosporine/tacrolimus blood levels and fluid balance should be closely
monitored.
----------------------------------------------------
[38]
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.
----------------------------------------------------
[39]
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
----------------------------------------------------
[40]
TÍTULO / TITLE: - Cryptococcus neoformans
infection in organ transplant recipients: variables influencing clinical
characteristics and outcome.
REVISTA
/ JOURNAL: - Emerg Infect Dis. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.cdc.gov/
●●
Cita: Emerging Infectious Diseases: <> 2001 May-Jun;7(3):375-81.
AUTORES
/ AUTHORS: - Husain S; Wagener MM; Singh N
INSTITUCIÓN
/ INSTITUTION: - Veterans Affairs Medical Center and
University of Pittsburgh, Thomas E. Starzl Transplantation Institute,
Pittsburgh, Pennsylvania 15240, USA.
RESUMEN
/ SUMMARY: - Unique clinical characteristics and other
variables influencing the outcome of Cryptococcus neoformans infection in organ
transplant recipients have not been well defined. From a review of published
reports, we found that C. neoformans infection was documented in 2.8% of organ
transplant recipients (overall death rate 42%). The type of primary immunosuppressive
agent used in transplantation influenced the predominant clinical manifestation
of cryptococcosis. Patients receiving tacrolimus were significantly less likely
to have central nervous system involvement (78% versus 11%, p =0.001) and more
likely to have skin, soft-tissue, and osteoarticular involvement (66% versus
21%, p = 0.006) than patients receiving nontacrolimus- based immunosuppression.
Renal failure at admission was the only independently significant predictor of
death in these patients (odds ratio 16.4, 95% CI 1.9-143, p = 0.004).
Hypotheses based on these data may elucidate the pathogenesis and may
ultimately guide the management of C. neoformans infection in organ transplant
recipients. N. Ref:: 74
----------------------------------------------------
[41]
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
----------------------------------------------------
[42]
TÍTULO / TITLE: - European best practice
guidelines for renal transplantation. Section IV: Long-term management of the
transplant recipient. IV.2.5. Chronic graft dysfunction. Late recurrence of
primary glomerulonephritides.
REVISTA
/ JOURNAL: - Nephrol Dial Transplant. Acceso gratuito
al texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://ndt.oupjournals.org/
●●
Cita: Nephrology Dialysis Transplantation: <> 2002;17 Suppl 4:16-8.
RESUMEN
/ SUMMARY: - GUIDELINES: A. In the case of recurrent
focal and segmental glomerulosclerosis (FSGS), aggressive treatment with
high-dose cyclosporine in children, ACE inhibitors and/or Angiotensin II
antagonists, plasma exchange or immunoadsorption may result in remission in
some patients. B. In the case of recurrent membranous nephropathy (MN), there
is no specific treatment. However, control of risk factors, such as
hypertension, heavy proteinuria and hyperlipidaemia, and prevention of
thrombotic complications are recommended. C. In the case of recurrent
membranoproliferative glomerulonephritis (MPGN), there is no specific
treatment. However, control of risk factors, such as hypertension, heavy
proteinuria and hyperlipidaemia, and prevention of thrombotic complications are
recommended. D. In the case of recurrent IgA glomerulonephritis, use of
additional steroids is not yet a validated treatment. The control of risk
factors, such as hypertension, heavy proteinuria and hyperlipidaemia, is
recommended. E. In the rare case of recurrent anti-glomerular basement membrane
(anti-GBM) glomerulonephritis with reappearance of anti-GBM antibodies, it is
recommended to initiate plasma exchange and to treat with appropriate
immunosuppressive agents (e.g. cyclophosphamide).
----------------------------------------------------
[43]
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
----------------------------------------------------
[44]
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
----------------------------------------------------
[45]
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
----------------------------------------------------
[46]
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
----------------------------------------------------
[47]
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
----------------------------------------------------
[48]
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
----------------------------------------------------
[49]
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
----------------------------------------------------
[50]
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,
----------------------------------------------------
[51]
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.
----------------------------------------------------
[52]
TÍTULO / TITLE: - Effects of tacrolimus
on ischemia-reperfusion injury.
REVISTA
/ JOURNAL: - Liver Transpl 2003 Feb;9(2):105-16.
●●
Enlace al texto completo (gratuito o de pago) 1053/jlts.2003.50020
AUTORES
/ AUTHORS: - St
Peter SD; Moss AA; Mulligan DC
INSTITUCIÓN
/ INSTITUTION: - Department of Transplant Surgery, Mayo Clinic
Scottsdale, AZ, USA.
RESUMEN
/ SUMMARY: - In addition to efficacious
immunosuppression for the benefit of organ transplantation, tacrolimus has
diverse actions that result in amelioration of ischemia-reperfusion injury.
Knowledge is accumulating rapidly on the mechanisms through which tacrolimus
exerts these cytoprotective effects, including alterations in microcirculation,
free radical metabolism, calcium-activated pathways, inflammatory cascades,
mitochondrial stability, apoptosis, stress-response proteins, and tissue
recovery. Within the nucleus, actions mediating the effects of tacrolimus
appear to be dominantly influenced by interactions with the transcription
factor, nuclear factor-kappaB. Because tacrolimus is a cornerstone agent in
immunosuppression regimens throughout the world and knowledge of its cellular
mechanisms is evolving, it is important to update the clinical literature with
this information. We reviewed the published literature with intent to portray
the interactions of tacrolimus in the intricate cellular mechanisms initiated
by ischemia and reperfusion. N.
Ref:: 122
----------------------------------------------------
[53]
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.
----------------------------------------------------
[54]
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
----------------------------------------------------
[55]
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.
----------------------------------------------------
[56]
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
----------------------------------------------------
[57]
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
----------------------------------------------------
[58]
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
----------------------------------------------------
[59]
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
----------------------------------------------------
[60]
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
----------------------------------------------------
[61]
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
----------------------------------------------------
[62]
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
----------------------------------------------------
[63]
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
----------------------------------------------------
[64]
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
----------------------------------------------------
[65]
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
----------------------------------------------------
[66]
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
----------------------------------------------------
[67]
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
----------------------------------------------------
[68]
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
----------------------------------------------------
[69]
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
----------------------------------------------------
[70]
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
----------------------------------------------------
[71]
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
----------------------------------------------------
[72]
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
----------------------------------------------------
[73]
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
----------------------------------------------------
[74]
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
----------------------------------------------------
[75]
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
----------------------------------------------------
[76]
- Castellano -
TÍTULO / TITLE:Presentacion de canceres en
receptores trasplantados con organo solido. Presentation of cancers in
recipients of a solid-organ transplant.
REVISTA
/ JOURNAL: - Nefrologia. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.aulamedica.es/nefrologia/
●●
Cita: Nefrologia: <> 2001;21(6):528-37.
AUTORES
/ AUTHORS: - Lampreabe I; Gomez-Ullate P; Amenabar JJ;
Zarraga S; Gainza FJ; Urbizu JM
INSTITUCIÓN
/ INSTITUTION: - Servicio de Nefrologia, Hospital de
Cruces, Facultad de Medicina, Universidad del Pais Vasco. ilampreave@hcru.osakidetza.net N. Ref:: 35
----------------------------------------------------
[77]
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.
----------------------------------------------------
[78]
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.
----------------------------------------------------
[79]
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
----------------------------------------------------
[80]
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
----------------------------------------------------
[81]
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
----------------------------------------------------
[82]
TÍTULO / TITLE: - Coadministration of
digoxin with itraconazole in renal transplant recipients.
REVISTA
/ JOURNAL: - Am J Kidney Dis 2001 Feb;37(2):E18.
AUTORES
/ AUTHORS: - Mathis AS; Friedman GS
INSTITUCIÓN
/ INSTITUTION: - Department of Pharmacy Practice and
Administration, College of Pharmacy, Rutgers, The State University of New
Jersey, College of Pharmacy, Piscataway, NJ, USA. smathis@sbhcs.com
RESUMEN
/ SUMMARY: - Digoxin toxicity is a major public health
issue in the United States. Often this is due to drug interactions, and renal
transplant recipients are at particularly high risk for drug-drug interactions.
We present cases of 2 renal transplant recipients who received itraconazole and
digoxin concomitantly and experienced digoxin toxicity. We have also reviewed
the relevant literature to elicit the mechanisms, signs, and symptoms of
digoxin toxicity in the presence of itraconazole. When clinicians know the
potential drug-drug interactions that may lead to digoxin toxicity, the
mechanisms of interaction, the signs and symptoms of digoxin toxicity, and
appropriate monitoring, digoxin toxicity is largely preventable. N. Ref:: 48
----------------------------------------------------
[83]
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
----------------------------------------------------
[84]
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
----------------------------------------------------
[85]
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
----------------------------------------------------
[86]
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
----------------------------------------------------
[87]
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
----------------------------------------------------
[88]
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
----------------------------------------------------
[89]
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
----------------------------------------------------
[90]
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
----------------------------------------------------
[91]
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
----------------------------------------------------
[92]
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
----------------------------------------------------
[93]
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
----------------------------------------------------
[94]
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.
----------------------------------------------------
[95]
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
----------------------------------------------------
[96]
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
----------------------------------------------------
[97]
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
----------------------------------------------------
[98]
TÍTULO / TITLE: - The role of newer
monoclonal antibodies in renal transplantation.
REVISTA
/ JOURNAL: - Transplant Proc 2001
Feb-Mar;33(1-2):1000-1.
AUTORES
/ AUTHORS: - Vincenti F
INSTITUCIÓN
/ INSTITUTION: - University of California, San Francisco,
California, USA. N.
Ref:: 5
----------------------------------------------------
[99]
TÍTULO / TITLE: - Molecular mechanisms of
renal allograft fibrosis.
REVISTA
/ JOURNAL: - Br J Surg 2001 Nov;88(11):1429-41.
●●
Enlace al texto completo (gratuito o de pago) 1046/j.0007-1323.2001.01867.x
AUTORES
/ AUTHORS: - Waller JR; Nicholson ML
INSTITUCIÓN
/ INSTITUTION: - Division of Transplant Surgery, University
of Leicester, Leicester, UK. julian@waller79.fsnet.co.uk
RESUMEN
/ SUMMARY: - BACKGROUND: Chronic graft nephropathy
(CGN) remains the leading cause of renal allograft loss after the first year
following transplantation. Histologically it is characterized by
glomerulosclerosis, intimal hyperplasia and interstitial fibrosis. The
pathogenesis is unclear, but is likely to involve both immunological and
non-immunological factors. Despite improvements in short-term graft survival
rates, new immunosuppressive regimens have made no impact on CGN. METHODS: A
review of the current literature on renal transplantation, novel
immunosuppression regimens and advances in the molecular pathogenesis of renal
allograft fibrosis was performed. RESULTS AND CONCLUSION: Recent advances in
understanding of the underlying molecular mechanisms involved suggest autocrine
secretion of cytokines and growth factors, especially transforming growth
factor beta, are associated with a change in fibroblast phenotype leading to
the deposition of extracellular matrix. Repeated insults trigger upregulation
of the tissue inhibitors of matrix metalloproteinases, favouring accumulation
of extracellular matrix. To date, no drug has proved effective in inhibiting or
reducing allograft fibrosis. The deleterious consequences of chronic
immunosuppression on the development of such fibrosis are now recognized; newer
immunosuppressive drugs, including rapamycin and mycophenolate mofetil, reduce profibrotic
gene expression in both experimental and clinical settings, and offer potential
strategies for prolonging allograft survival.
N. Ref:: 155
----------------------------------------------------
[100]
TÍTULO / TITLE: - Immunologic risk
factors for chronic renal allograft dysfunction.
REVISTA
/ JOURNAL: - Transplantation 2001 Jun 15;71(11
Suppl):SS17-23.
AUTORES
/ AUTHORS: - Paul LC
INSTITUCIÓN
/ INSTITUTION: - Leiden University Medical School, The
Netherlands.
RESUMEN
/ SUMMARY: - Tissue injury is probably the central
feature leading to CRAD, whether that injury is produced by immunological or
nonimmunological factors. Tissue injury may expose cryptic antigens that, in an
allogeneic situation, stimulate immune responses that further increase tissue
damage. With acute rejection the immunological factor most strongly predictive
of CRAD, HLA mismatches may facilitate rejection or otherwise lead to CRAD.
However, clinical studies have not always demonstrated an increasing risk of
CRAD with increased numbers of HLA mismatches. Antibodies produced against HLA
or other donor-specific antigens may play a role in initiating the CRAD process
or may occur secondary to tissue damage. Several human transplant studies have
demonstrated an association between anti-HLA or anti-B cell antibodies and
CRAD. In animal models of CRAD, antibodies are produced against antigens
associated with glomerular and tubular basement membranes and mesangial cells,
as well as antigens associated with vascular endothelial cells. The
pathogenetic significance of these antibody responses is unclear at this time,
but these responses may interfere with repair processes that follow tissue
injury or otherwise facilitate mechanisms leading to CRAD. Whether similar
antibody responses against components of basement membrane and mesangial cells
occur in human renal transplant patients with CRAD is not yet known. The most
effective way to prevent CRAD is to prevent tissue damage, especially
immunity-related injury that involves maintaining appropriate
immunosuppression. When using calcineurin inhibitors for immunosuppression,
there is a risk of chronic calcineurin inhibitor-associated nephrotoxicity.
Nonnephrotoxic immunosuppressive agents, such as sirolimus and mycophenolate
mofetil, may be considered in therapeutic strategies designed to prevent acute
rejection and to minimize renal tissue damage due to nephrotoxic drugs. N. Ref:: 54
----------------------------------------------------
[101]
TÍTULO / TITLE: - Daclizumab: a review of
its use in the management of organ transplantation.
REVISTA
/ JOURNAL: - BioDrugs 2001;15(11):745-73.
AUTORES
/ AUTHORS: - Carswell CI; Plosker GL; Wagstaff AJ
INSTITUCIÓN
/ INSTITUTION: - Adis International Limited, Auckland, New
Zealand. demail@adis.co.nz
RESUMEN
/ SUMMARY: - The humanised monoclonal antibody
daclizumab is an immunosuppressive agent that reduces acute rejection in solid
organ transplantation. It is specific for the alpha subunit (Tac/CD25) of the
interleukin (IL)-2 receptor on activated T cells and achieves immunosuppression
by competitive antagonism of IL-2-induced T cell proliferation. When added to
standard triple immunosuppression regimens, daclizumab significantly reduces
the rate of acute rejection at 1 year in renal transplantation by 36% and there
are indications that it may be effective in other solid organ transplantations.
Three-year outcomes of two phase III clinical trials in renal transplantation
indicate similar values for graft and patient survival between daclizumab and
placebo when given in addition to triple immunosuppression; however, these
pivotal trials were not designed with sufficient power to demonstrate any
statistical significance. The addition of daclizumab induction shows potential
in allowing calcineurin inhibitor- and corticosteroid-sparing regimens without
increasing the rate of acute graft rejection or adverse effects in renal and
liver transplantation. Preliminary reports indicate that daclizumab may also be
a useful agent in delayed graft function and graft versus host disease (GVHD).
Further investigation of its efficacy in these groups and in children is
needed. Data from clinical trials show daclizumab to be well tolerated in solid
organ transplantation. It does not increase the incidence of infection,
including cytomegalovirus infection, when compared with placebo or no induction
groups. Preliminary comparative data with muromonab CD3 indicate that
daclizumab may be associated with a lower rate of infectious complications and
similar or better efficacy. CONCLUSIONS: In conclusion, daclizumab has been
proven to reduce acute rejection in renal transplant recipients when given in
addition to traditional baseline immunosuppression. It has shown potential to
reduce acute rejection in other solid organ transplants; however, well
designed, randomised studies are required to confirm this. Clinical experience
from trials to date indicate that daclizumab has a tolerability profile similar
to placebo with no significant effect on the incidence of infection. The
relative efficacy and tolerability of daclizumab compared with other induction
agents has yet to be defined. Available data suggest that daclizumab may allow
the use of calcineurin inhibitor-sparing and corticosteroid-sparing regimens
and may have potential in the treatment of GVHD. N. Ref:: 80
----------------------------------------------------
[102]
TÍTULO / TITLE: - In-stent stenosis:
pathology and implications for the development of drug eluting stents.
REVISTA
/ JOURNAL: - Heart 2003 Feb;89(2):218-24.
AUTORES
/ AUTHORS: - Bennett MR
INSTITUCIÓN
/ INSTITUTION: - Addenbrooke’s Centre for Clinical
Investigation, Box 110, Addenbrooke’s Hospital, Cambridge CB2 2QQ, UK. mrb@mole.bio.cam.ac.uk N. Ref:: 20
----------------------------------------------------
[103]
TÍTULO / TITLE: - Kidney transplantation
during the first trimester of pregnancy: immunosuppression with mycophenolate
mofetil, tacrolimus, and prednisone.
REVISTA
/ JOURNAL: - Transplantation 2001 Apr 15;71(7):994-7.
AUTORES
/ AUTHORS: - Pergola PE; Kancharla A; Riley DJ
INSTITUCIÓN
/ INSTITUTION: - Department of Medicine, University of
Texas Health Science Center at San Antonio, 78229, USA.
RESUMEN
/ SUMMARY: - We present a case of living, related-donor
kidney transplantation during the first trimester of pregnancy. The patient
received mycophenolate mofetil (MMF), tacrolimus, and prednisone throughout the
entire pregnancy. This is the first reported case of use of MMF during
pregnancy. The mother did well, except for mild preeclampsia and mild renal
insufficiency at term. The baby girl was born prematurely at week 353/7. The
only possible teratogenic effects detected included hypoplastic nails and short
fifth fingers. No chromosomal abnormalities were found. The child is growing
and developing normally. Although we do not recommend the use of mycophenolate
mofetil during pregnancy based on this experience, it is reassuring to know
that a successful outcome can be expected in mothers treated with MMF during
pregnancy. N. Ref:: 10
----------------------------------------------------
[104]
TÍTULO / TITLE: - Atopic dermatitis
management with tacrolimus ointment (Protopic).
REVISTA
/ JOURNAL: - J Dermatolog Treat 2003;14(Suppl 1):5-16.
AUTORES
/ AUTHORS: - Kapp A; Allen BR; Reitamo S
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology and Allergology,
Hannover Medical University, Hannover, Germany. Kapp.Alexander@MH-Hannover.de
RESUMEN
/ SUMMARY: - Tacrolimus ointment is the first of a new
class of non-steroidal topical immunomodulators indicated for the treatment of
atopic dermatitis. Topical tacrolimus has been subject to an extensive clinical
development program involving more than 16,000 patients. A clinical trial
program, including vehicle-controlled studies, short- and long-term comparative
studies and long-term safety studies, has investigated tacrolimus 0.1% and
0.03% ointment for the treatment of atopic dermatitis in adults and children
aged 24 months and older. Tacrolimus monotherapy is rapidly effective,
resulting in clinical improvements within three days of starting therapy, and
produces a progressive increase in efficacy that is sustained during long-term
treatment. Tacrolimus treats the signs and symptoms of atopic dermatitis,
reduces the incidence of flares, and offers the potential for long-term disease
control. No major safety concerns have been reported to date. Tacrolimus
ointment is generally well tolerated, the primary adverse events being mild to
moderate and transient application-site reactions: skin burning, pruritus and
erythema. Tacrolimus ointment is a significant advance in dermatology and
provides physicians with an alternative to conventional topical corticosteroid
therapy. N. Ref:: 41
----------------------------------------------------
[105]
TÍTULO / TITLE: - Strategies to reduce
toxicities and improve outcomes in renal transplant recipients.
REVISTA
/ JOURNAL: - Pharmacotherapy 2002 Mar;22(3):316-28.
AUTORES
/ AUTHORS: - Lo A; Alloway RR
INSTITUCIÓN
/ INSTITUTION: - Department of Surgery, University of
Cincinnati Medical Center, Ohio 45267-0585, USA.
RESUMEN
/ SUMMARY: - Ongoing improvements in immunosuppression
and posttransplantation care have dramatically improved patient and graft
outcomes after transplantation. The frequency of graft loss due to acute
rejection has declined considerably as a result of the availability of a
variety of more potent immunosuppressive agents and probably also because of
refined clinical care and follow-up. Complications of long-term administration
of corticosteroids (steroids) and calcineurin inhibitors, however, have become
increasingly apparent as patients live longer with their transplant, and
attention is shifting to long-term issues. Use of both steroids and calcineurin
inhibitors is associated with metabolic toxicities such as hypertension,
hyperlipidemia, diabetes, bone loss, and cataracts. These contribute to
posttransplantation morbidity and may negatively affect patient and allograft
survival. A variety of troublesome cosmetic side effects, such as hirsutism,
gingival hyperplasia, alopecia, obesity, and cushingoid appearance, also are
associated with these drugs. These effects can detract from patient self-esteem
and compliance with the immunosuppressive regimen. In the past 2 decades, the
introduction of second-generation immunosuppressive drugs, such as tacrolimus,
mycophenolate mofetil, sirolimus, and anti-interleukin-2 receptor monoclonal
antibodies, has provided some alternatives to classic immunosuppressant
choices. Patients experiencing undesirable adverse events now can be converted
to another immunosuppressive regimen that ultimately will improve graft and
patient survival rates and improve quality of life after transplantation. N. Ref:: 99
----------------------------------------------------
[106]
TÍTULO / TITLE: - Infectious
complications in SLE after immunosuppressive therapies.
REVISTA
/ JOURNAL: - Curr Opin Rheumatol 2003 Sep;15(5):528-34.
AUTORES
/ AUTHORS: - Kang I; Park SH
INSTITUCIÓN
/ INSTITUTION: - Section of Rheumatology, Yale University
School of Medicine, New Haven, Connecticut 06520, USA. insoo.kang@yale.edu
RESUMEN
/ SUMMARY: - Immunosuppressive drugs have become the
gold standard for the treatment of major organ involvement in systemic lupus
erythematosus. The use of immunosuppressive therapy in systemic lupus
erythematosus carries significant risks for infection. This article reviews
infectious complications in systemic lupus erythematosus, focusing on effects
of immunosuppressive therapy. Patients with systemic lupus erythematosus appear
to carry an intrinsically increased risk for infection. Recent studies support
this notion further by showing increased risk for serious infections in
patients with systemic lupus erythematosus who had mannose-binding lectin
deficiency associated with homozygous mannose-binding lectin variant alleles.
Patients with systemic lupus erythematosus who were homozygous for
mannose-binding lectin variant alleles had a fourfold increase in the incidence
of infections, requiring hospitalization. In terms of extrinsic risk factors
for infection, use of steroids and cyclophosphamide are the strongest risk
factors. The effect of these drugs on infection is also dose dependent. The
incidence of infectious complications in patients treated with mycophenolate
mofetil, a newly used immunosuppressive drug in systemic lupus erythematosus,
appears less frequent compared with cyclophosphamide. Herpes zoster is still
the most common viral infection in patients with systemic lupus erythematosus
treated with cyclophosphamide and mycophenolate mofetil. Overall data indicate
that patients with systemic lupus erythematosus may have intrinsically
increased risks for infection that are augmented by immunosuppressive
therapies. Cyclophosphamide, in particular in combination with high-dose
glucocorticoids, has the strongest effect in suppressing the immune responses
against microorganisms. Careful monitoring of infectious complications is
warranted in patients with systemic lupus erythematosus receiving
immunosuppressive therapies, in particular those on high-dose glucocorticoids
and cytotoxic drugs. N.
Ref:: 87
----------------------------------------------------
[107]
TÍTULO / TITLE: - Successful
hematopoietic stem cell transplantation for aplastic anemia following
living-related liver transplantation.
REVISTA
/ JOURNAL: - Bone Marrow Transplant 2002 Oct;30(8):531-4.
●●
Enlace al texto completo (gratuito o de pago) 1038/sj.bmt.1703689
AUTORES
/ AUTHORS: - Umeda K; Adachi S; Watanabe K; Kimura N;
Lin Y; Nakahata T
INSTITUCIÓN
/ INSTITUTION: - Department of Pediatrics, Graduate School
of Medicine, Kyoto University, Kyoto, Japan.
RESUMEN
/ SUMMARY: - A 1-year-old boy received a living-related
liver transplantation (LRLT) from his HLA-haploidentical father to treat acute
liver failure following non-A, non-B, non-C hepatitis. He subsequently
developed pancytopenia and was diagnosed with aplastic anemia (AA). He was
platelet transfusion dependent and developed two episodes of life-threatening
intracranial hemorrhage despite immuno-suppressive therapy consisting of
cyclosporin A, antithymocyte globulin, and anabolic steroids. He received
combined hematopoietic stem cell transplantation (hSCT) with cord blood and
bone marrow from an HLA-matched sibling. Conditioning consisted of
cyclophosphamide (CY) 200 mg/kg and 7 Gy total lymphoid irradiation (TLI).
Marrow engraftment was prompt and there was no significant graft-versus-host
disease (GVHD). N.
Ref:: 10
----------------------------------------------------
[108]
TÍTULO / TITLE: - Tacrolimus: a further
update of its use in the management of organ transplantation.
REVISTA
/ JOURNAL: - Drugs 2003;63(12):1247-97.
AUTORES
/ AUTHORS: - Scott LJ; McKeage K; Keam SJ; Plosker GL
INSTITUCIÓN
/ INSTITUTION: - Adis International Limited, Auckland, New
Zealand. demail@adis.co.nz
RESUMEN
/ SUMMARY: - Extensive clinical use has confirmed that
tacrolimus (Prograf) is a key option for immunosuppression after
transplantation. In large, prospective, randomised, multicentre trials in
adults and children receiving solid organ transplants, tacrolimus was at least
as effective or provided better efficacy than cyclosporin microemulsion in
terms of patient and graft survival, treatment failure rates and the incidence
of biopsy-proven acute and corticosteroid-resistant rejection episodes.
Notably, the lower incidence of rejection episodes after renal transplantation
in tacrolimus recipients was reflected in improved cost effectiveness. In bone
marrow transplant (BMT) recipients, the incidence of tacrolimus grade II-IV
graft-versus-host disease was significantly lower with tacrolimus than
cyclosporin treatment. Efficacy was maintained in renal and liver transplant
recipients after total withdrawal of corticosteroid therapy from tacrolimus-based
immunosuppression, with the incidence of acute rejection episodes at up to 2
years’ follow-up being similar with or without corticosteroids. Tacrolimus
provided effective rescue therapy in transplant recipients with persistent
acute or chronic allograft rejection or drug-related toxicity associated with
cyclosporin treatment. Typically, conversion to tacrolimus reversed rejection
episodes and/or improved the tolerability profile, particularly in terms of
reduced hyperlipidaemia. In lung transplant recipients with obliterative
bronchiolitis, conversion to tacrolimus reduced the decline in and/or improved
lung function in terms of forced expiratory volume in 1 second. Tolerability
issues may be a factor when choosing a calcineurin inhibitor. Cyclosporin tends
to be associated with a higher incidence of significant hypertension,
hyperlipidaemia, hirsutism, gingivitis and gum hyperplasia, whereas the
incidence of some types of neurotoxicity, disturbances in glucose metabolism,
diarrhoea, pruritus and alopecia may be higher with tacrolimus treatment. Renal
function, as assessed by serum creatinine levels and glomerular filtration
rates, was better in tacrolimus than cyclosporin recipients at up to 5 years’
follow-up. CONCLUSION: Recent well designed trials have consolidated the place
of tacrolimus as an important choice for primary immunosuppression in solid
organ transplantation and in BMT. Notably, in adults and children receiving
transplants, tacrolimus-based primary immunosuppression was at least as effective
or provided better efficacy than cyclosporin microemulsion treatment in terms
of patient and graft survival, treatment failure and the incidence of acute and
corticosteroid-resistant rejection episodes. The reduced incidence of rejection
episodes in renal transplant recipients receiving tacrolimus translated into a
better cost effectiveness relative to cyclosporin microemulsion treatment. The
optimal immunosuppression regimen is ultimately dependent on balancing such
factors as the efficacy of the individual drugs, their tolerability, potential
for drug interactions and pharmacoeconomic issues. N. Ref:: 261
----------------------------------------------------
[109]
TÍTULO / TITLE: - Alternariosis after
liver transplantation.
REVISTA
/ JOURNAL: - Transplantation 2001 Dec 15;72(11):1840-3.
AUTORES
/ AUTHORS: - Benito N; Moreno A; Puig J; Rimola A
INSTITUCIÓN
/ INSTITUTION: - Institut Clinic d’ Infeccions i
Inmunologia, IDIBAPS, Hospital Clinic, Universitat de Barcelona, España. nbenito@clinic.ub.es
RESUMEN
/ SUMMARY: - Alternaria is a saprophytic fungus that is
increasingly recognized as a human pathogen, particularly in immunocompromised
hosts, including solid-organ transplant recipients. Although combined surgical
and medical treatment seem to be useful in the management of this infection, an
optimal antifungal therapy remains to be defined. Only four cases of
alternariosis after orthotopic liver transplantation have been reported. We
describe an additional case and review the literature on infections due to
Alternaria in organ transplant recipients, with special emphasis on
treatment. N. Ref:: 20
----------------------------------------------------
[110]
TÍTULO / TITLE: - Resistance to
rapamycin: a novel anticancer drug.
REVISTA
/ JOURNAL: - Cancer Metastasis Rev 2001;20(1-2):69-78.
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: - The macrocyclic lactone rapamycin has an
established place as an immune suppressive agent in organ transplantation.
However, more recently it has been recognized as an inhibitor of pathways that
may be activated during malignant transformation and tumor progression. Thus,
increasing interest is being directed to this class of antibiotic as potential
antitumor agents. Here we summarize the history, mechanism of action, and
mechanisms of resistance to rapamycin. N.
Ref:: 92
----------------------------------------------------
[111]
TÍTULO / TITLE: - Subcutaneous infection
with Mycobacterium fortuitum after allogeneic bone marrow transplantation.
REVISTA
/ JOURNAL: - Bone Marrow Transplant 2001
Oct;28(7):709-11.
●●
Enlace al texto completo (gratuito o de pago) 1038/sj/bmt/1703211
AUTORES
/ AUTHORS: - Okano A; Shimazaki C; Ochiai N; Hatsuse M;
Takahashi R; Ashihara E; Inaba T; Fujita N; Noda Y; Nakagawa M
INSTITUCIÓN
/ INSTITUTION: - Second Department of Medicine, Kyoto
Prefectural University of Medicine, 465 Kawaramachi-Hirokoji, Kami-gyoku,
Kyoto, 602-8566, Japan.
RESUMEN
/ SUMMARY: - Reports of cases of mycobacterial
infections after SCT are rare. We report a 30-year-old female with a cutaneous
infection of Mycobacterium fortuitum 30 months after allogeneic bone marrow
transplantation for acute lymphoblastic leukemia. The patient was successfully
treated with surgical debridement followed by oral minocycline and
clarithromycin. Mycobacterial infections should be considered in SCT patients
with undiagnosed refractory chronic cutaneous infection, and surgical
debridement is useful for the diagnosis and treatment of such infections. N. Ref:: 7
----------------------------------------------------
[112]
TÍTULO / TITLE: - Evolution of
immunosuppression and continued importance of acute rejection in renal
transplantation.
REVISTA
/ JOURNAL: - Am J Kidney Dis 2001 Dec;38(6 Suppl
6):S2-9.
AUTORES
/ AUTHORS: - Chan L; Gaston R; Hariharan S
INSTITUCIÓN
/ INSTITUTION: - Department of Renal Medicine, University
of Colorado Health Sciences Center, Denver, CO 80262, USA. Larry.Chan@uchsc.edu
RESUMEN
/ SUMMARY: - As steady improvement in short-term kidney
graft survival and long-term outcomes prolongs the lives of transplant
patients, responsibility for their care is shifting away from transplant
specialists and into the hands of community nephrologists. Therefore, community
nephrologists need to have a deeper understanding of immunosuppressive
therapies than ever before. Pharmacologic immunosuppression has been
continuously evolving over the past two decades. Azathioprine was introduced in
the early 1960s. Introduction of cyclosporine (CsA) in 1983 revolutionized
short-term outcomes after renal transplantation. The first monoclonal antibody
immunosuppressant, OKT3, was introduced in 1986. The 1990s saw the introduction
of a number of important new agents, including mycophenolate mofetil (MMF),
tacrolimus, and a microemulsion CsA, as well as two new monoclonal antibodies.
Combinations of these new agents, along with improving clinical care, have
produced 1-year patient survival approaching 100% and graft survival exceeding
90%. The newest class of agents, the first of which is sirolimus, is called
target of rapamycin (TOR) inhibitors and is used with CsA for maintenance
therapy. Immunosuppressive drug therapy after kidney transplantation continues
to evolve. There is a variety of pharmacologic combinations from which to
choose, based on immunologic risk and side effect profiles. As new regimens are
developed, ongoing communications between the transplant center and community
nephrologists will be required to implement therapeutic changes and optimize
patient care successfully. N.
Ref:: 59
----------------------------------------------------
[113]
TÍTULO / TITLE: - Post-liver transplant
obesity and diabetes.
REVISTA
/ JOURNAL: - Curr Opin Clin Nutr Metab Care 2003
Jul;6(4):457-60.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.mco.0000078994.96795.d8
AUTORES
/ AUTHORS: - T D
Correia MI; Rego LO; Lima AS
INSTITUCIÓN
/ INSTITUTION: - Alfa Institute of Gastroenterology,
University Hospital, Federal University of Minas Gerais, Brazil. Isabel_correia@uol.com.br
RESUMEN
/ SUMMARY: - PURPOSE OF REVIEW: Post-liver transplant
patients present a vast array of metabolic changes in the early and late phase
which impact on their morbidity and mortality. The development of obesity and
diabetes in these patients has been widely described in the literature with
several hypotheses suggested: liver donor, nutritional and metabolic state, and
immunosuppressive drugs. RECENT FINDINGS: Most that is known about the
development of these metabolic derangements has been attributed to the drugs
used, especially the corticosteroids. When these have been used in higher doses
for longer periods to treat rejection, the incidence of diabetes and obesity
seems to be higher. However cyclosporine and to a lesser extent tacrolimus are
also related to these alterations. SUMMARY: As long-term survival improves in
liver transplant patients, cardiovascular complications associated with
dyslipidemia, obesity, and diabetes are emerging as risk factors for late
morbidity and mortality. Therefore, it is important to assess the potential
risk factors related to these complications, in order to prevent or decrease
their incidence. From what has been seen, immunossupressive drugs seem to be
the greatest risk factor for the development of metabolic derangements in
post-transplantation patients. However other risk factors might also be
involved, such as non-healthy eating habits and lack of exercise. The latter
can be preventable if counseling policies are targeted at these patients in the
pre-transplantation phase and continued after the operation. N. Ref:: 27
----------------------------------------------------
[114]
TÍTULO / TITLE: - Decreasing side effects
of Neoral through three-times-a-day protocol in Chinese renal transplant
patients.
REVISTA
/ JOURNAL: - Transplant Proc 2001
Nov-Dec;33(7-8):3156-7.
AUTORES
/ AUTHORS: - Chen ZS; Zeng FJ; Lin ZB; Chen ZK; Sha B;
Wen ZX; Ming CS; Zhang WJ; Xia SS
INSTITUCIÓN
/ INSTITUTION: - Institute of Organ Transplantation, Tongji
Hospital, Tongji Medical College, Huazhong University of Science and
Technology, Wuhan, China.
----------------------------------------------------
[115]
TÍTULO / TITLE: - Influence of
cyclosporin, tacrolimus and rapamycin on renal function and arterial
hypertension after renal transplantation.
REVISTA
/ JOURNAL: - Nephrol Dial Transplant. Acceso gratuito
al texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://ndt.oupjournals.org/
●●
Cita: Nephrology Dialysis Transplantation: <> 2001;16 Suppl 1:121-4.
AUTORES
/ AUTHORS: - Morales JM; Andres A; Rengel M; Rodicio JL
INSTITUCIÓN
/ INSTITUTION: - Renal Transplant Unit, Nephrology
Department, Hospital 12 de Octubre, Madrid, España.
RESUMEN
/ SUMMARY: - Cyclosporin and tacrolimus have improved
survival figures in organ transplantation. However, both drugs are potentially
nephrotoxic. The immunosuppressive and nephrotoxic effects of both drugs appear
to depend on the inhibition of calcineurin. Cyclosporin and tacrolimus cause
acute (functional changes) and chronic nephrotoxicity (structural lesions in
the kidney). These last important lesions include arteriolar hyalinosis,
stripped interstitial fibrosis and tubular atrophy. It is possible that
repeated episodes of renal ischaemia contribute to the development of chronic
nephrotoxicity and then chronic allograft nephropathy. Cyclosporin and
tacrolimus also induce arterial hypertension. Therefore, the beneficial effects
of immunosuppression have been limited due to nephrotoxicity and arterial
hypertension. Rapamycin, a novel immunosuppressive agent, that does not inhibit
calcineurin, provides immunosuppression without nephrotoxicity. In fact, in the
trials performed in Europe, sirolimus-treated immunosuppression patients
exhibited a much better renal function than cyclosporin-treated patients.
However, sirolimus can potentiate the nephrotoxic effect of cyclosporin.
Therefore, when cyclosporin and sirolimus are used in combination, a reduction
of the cyclosporin dose is desirable. N.
Ref:: 28
----------------------------------------------------
[116]
TÍTULO / TITLE: - Sirolimus-based
immunosuppressive [correction of immunosuppresive] protocol for calcineurin
sparing in liver transplantation.
REVISTA
/ JOURNAL: - Transplant Proc 2002 Aug;34(5):1522-3.
AUTORES
/ AUTHORS: - Heffron TG; Smallwood GA; Davis L;
Martinez E; Stieber AC
INSTITUCIÓN
/ INSTITUTION: - Department of Surgery, Emory University
School of Medicine, Atlanta, GA 30322, USA.
----------------------------------------------------
[117]
TÍTULO / TITLE: - Immunosuppressive drug
use in pregnancy.
REVISTA
/ JOURNAL: - Autoimmunity 2003 Feb;36(1):51-6.
AUTORES
/ AUTHORS: - Petri M
INSTITUCIÓN
/ INSTITUTION: - Johns Hopkins University School of
Medicine, 1830 E. Monument Street, Suite 7500, Baltimore, MD 21205, USA.
RESUMEN
/ SUMMARY: - Ideally, immunosuppressive drugs would not
be necessary in pregnancy. However, in connective tissue disease (especially
systemic lupus erythematosus, SLE) vasculitis, and sometimes antiphospholipid
antibody syndrome, their use is necessary both to protect the health of the
mother and to insure the success of the pregnancy. The more commonly used drugs
will be reviewed, with an emphasis on human data, when available. Methotrexate
and leflunamide will not be considered, for they should never be used in
pregnancy. N. Ref:: 105
----------------------------------------------------
[118]
TÍTULO / TITLE: - Immunosuppression
protocols for HLA identical renal transplant recipients.
REVISTA
/ JOURNAL: - Transplant Proc 2003 May;35(3):1074-5.
AUTORES
/ AUTHORS: - Keitel E; Santos AF; Alves MA; Neto JP;
Schaefer PG; Bittar AE; Goldani JC; Pozza R; Bruno RM; See D; Garcia CD; Garcia
VD
INSTITUCIÓN
/ INSTITUTION: - Renal Transplant Unit, Santa Casa
Hospital, Porto Alegre, RS, Brazil. keitel@terra.com.br
----------------------------------------------------
[119]
TÍTULO / TITLE: - Improving tolerability
of immunosuppressive regimens.
REVISTA
/ JOURNAL: - Transplantation 2001 Dec 27;72(12
Suppl):S105-12.
AUTORES
/ AUTHORS: - MacDonald A
RESUMEN
/ SUMMARY: - CNIs and corticosteroids are associated
with adverse effects that can diminish quality of life and detrimentally affect
long-term allograft and patient survival. Nephrotoxicity is the major side
effect of CNI therapy. A search has been ongoing for improved immunosuppressive
regimens that will provide adequate protection against acute allograft
rejection, while decreasing the nephrotoxic and other effects associated with
CNIs. This paper reviewed the immunosuppressive agent sirolimus as a potential
new option in transplantation, focusing on its mechanism of action and clinical
efficacy as well as potential antiproliferative and antineoplastic properties.
The findings and lessons learned from key clinical studies in which sirolimus
was used to augment or replace CNIs and/or corticosteroids were highlighted,
and the importance of clinical pharmacokinetics and therapeutic drug monitoring
in these regimens were discussed. Preliminary studies of combination therapy
with sirolimus and tacrolimus in solid organ transplantation indicate that
sirolimus/tacrolimus combination therapy may provide strong protection against
acute rejection and diminish the nephrotoxicity associated with CNI-based
therapy. Other studies suggest that sirolimus can be used as base
immunosuppressive therapy, thereby completely avoiding the nephrotoxicity
associated with CNI-based therapies, while continuing to provide powerful
protection against rejection. With patients surviving longer with functional
allografts, quality of life is becoming an increasing important clinical
endpoint in transplantation. The studies reviewed here suggest that sirolimus
might be used to improve quality of life significantly without increasing the
risk of allograft rejection or shortening patient survival. N. Ref:: 73
----------------------------------------------------
[120]
TÍTULO / TITLE: - Technical and
immunosuppressive advances in transplantation for insulin-dependent diabetes
mellitus.
REVISTA
/ JOURNAL: - World J Surg 2002 Feb;26(2):194-211. Epub
2001 Dec 17.
●●
Enlace al texto completo (gratuito o de pago) 1007/s00268-001-0207-0
AUTORES
/ AUTHORS: - Odorico JS; Sollinger HW
INSTITUCIÓN
/ INSTITUTION: - Division of Organ Transplantation,
Department of Surgery, University of Wisconsin Hospital and Clinics, H4/756
Clinical Science Center, 600 Highland Avenue, Madison,Wisconsin 53792, USA. jon@tx.surgery.wisc.edu
RESUMEN
/ SUMMARY: - Pancreas transplantation has emerged as
the single most effective way to achieve normal glucose homeostasis inpatients
with type I insulin-dependent diabetes mellitus. Optimal immunosuppressive
strategies for pancreas transplantation continue to evolve with the use of
newer, more potent immunosuppressive agents,particularly tacrolimus,
mycophenolate mofetil, and rapamycin. These agents have contributed to
substantially lower rates of allograft rejection and improved graft survival.
Regimens designed to avoid nephrotoxicity or spare corticosteroid therapy are
emerging as the variety of drug options grows. Also contributing to
progressively better results for solitary pancreas transplants are reductions
in early graft loss rates and the development of safe, effective biopsy
techniques, permitting accurate diagnosis of rejection. Collectively,these
factors have allowed solitary pancreas allograft recipients, a group of
patients with historically poor long-term graft survival, to enjoy successes
nearly equivalent to those of combined kidney-pancreas transplants.
Consequently, the American Diabetes Association strongly endorses pancreas
transplantation in diabetic patients who have received prior kidney transplants
and who have life-threatening metabolic lability. N. Ref:: 189
----------------------------------------------------
[121]
TÍTULO / TITLE: - The impact of late
acute rejection after cadaveric kidney transplantation.
REVISTA
/ JOURNAL: - Clin Transplant 2001 Aug;15(4):221-7.
AUTORES
/ AUTHORS: - Joseph JT; Kingsmore DB; Junor BJ; Briggs
JD; Mun Woo Y; Jaques BC; Hamilton DN; Jardine AG; Jindal RM
INSTITUCIÓN
/ INSTITUTION: - Department of Transplantation Surgery,
University of Glasgow and the Western Infirmary, Glasgow, UK.
RESUMEN
/ SUMMARY: - BACKGROUND: Acute graft rejection (AR)
following renal transplantation results in reduced graft survival. However,
there is uncertainty regarding the definition, aetiology and long-term graft
and patient outcome of AR occurring late in the post-transplant period. AIM: To
determine if rejection episodes can be classified by time from transplantation
by their impact on graft survival into early acute rejection (EAR) and late
acute rejection (LAR). MATERIALS AND METHODS: 687 consecutive adult renal
transplant recipients who received their first cadaveric renal transplant at a
single centre. All received cyclosporine (CyA)-based immunosuppression, from
1984 to 1996, with a median follow-up of 6.9 yr. Details were abstracted from clinical
records, with emphasis on age, sex, co-morbid conditions, HLA matching,
rejection episodes, patient and graft survival. ANALYSIS: Patients were
classified by the presence and time to AR from the date of transplantation.
Using those patients who had no AR (NAR) as a baseline, we determined the
relative risk of graft failure by time to rejection. The characteristics of
patients who had no rejection, EAR and LAR were compared. RESULTS: Compared
with NAR, the risk of graft failure was higher for those patients who suffered
a rejection episode. A much higher risk of graft failure was seen when the
first rejection episode occurred after 90 d. Thus, a period of 90 d was taken
to separate EAR and LAR (relative risk of 3.06 and 5.27 compared with NAR as
baseline, p<0.001). Seventy-eight patients (11.4%) had LAR, 271 (39.4%) had
EAR and 338 (49.2%) had NAR. The mean age for each of these groups differed
(LAR 39.6 yr, EAR 40.8 yr compared with NAR 44 yr, p<0.003). The 5-yr graft
survival for those who had LAR was 45% and 10-yr survival was 28%. HLA
mismatches were more frequent in those with EAR vs. NAR (zero mismatches in
HLA-A: 36 vs. 24%, HLA-B: 35 vs. 23% and HLA-DR: 63 vs. 41%, p<0.003). There
was no difference in mismatching frequency between NAR and LAR. CONCLUSIONS: AR
had a deleterious impact on graft survival, particularly if occurring after 90
d. AR episodes should therefore be divided into early and late phases. In view
of the very poor graft survival associated with LAR, it is important to gain
further insight into the main aetiological factors. Those such as suboptimal
CyA blood levels and non-compliance with medication should be further
investigated with the aim of developing more effective immunosuppressive
regimens in order to reduce the incidence of LAR. N. Ref:: 35
----------------------------------------------------
[122]
TÍTULO / TITLE: - Systemic management of
posterior uveitis.
REVISTA
/ JOURNAL: - J Ocul Pharmacol Ther 2003
Aug;19(4):325-43.
●●
Enlace al texto completo (gratuito o de pago) 1089/108076803322279381
AUTORES
/ AUTHORS: - Song J
INSTITUCIÓN
/ INSTITUTION: - Duke University Medical Center, Durham, NC
27710, USA. Song0012@notes.duke.edu
RESUMEN
/ SUMMARY: - In the treatment of uveitis,
corticosteroids are usually included in first-line therapy due to its rapid
onset of action and excellent safety profile. Systemic immunosuppressive agents
also play an important role in the management of posterior uveitis. The purpose
of this study was to review systemic agents for treating uveitis: prednisone,
methotrexate, cyclosporine, and azathioprine. This study was a review of the
literature using Medline. Thirty-eight references were incorporated.
Immunosuppressants take several weeks for their full effect and are considered
when long-term therapy is anticipated. When long-term therapy is anticipated,
immunosuppressant agents may be added, which allows for the reduction and eventual
discontinuation of prednisone. Combination therapy of various
immunosuppressants also allows for long-term therapy, which reduces the relapse
rate. However, immunosuppressives can be associated with serious side-effects.
The use of immunosuppressants requires careful monitoring. N. Ref:: 38
----------------------------------------------------
[123]
TÍTULO / TITLE: - Malignancy and renal
disease.
REVISTA
/ JOURNAL: - Crit Care Clin 2001 Jul;17(3):571-98,
viii.
AUTORES
/ AUTHORS: - Kapoor M; Chan GZ
INSTITUCIÓN
/ INSTITUTION: - Department of Anesthesiology and Critical
Care Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
RESUMEN
/ SUMMARY: - A variety of renal diseases and
electrolyte disorders may be associated with various malignancies or with
treatment of malignancy with chemotherapeutic drugs or radiation. This article
reviews renal disease in cancer patients, which constitutes a major source of
morbidity and mortality. N.
Ref:: 207
----------------------------------------------------
[124]
TÍTULO / TITLE: - Immunosuppressive drugs
and cancer.
REVISTA
/ JOURNAL: - Toxicology 2003 Apr 1;185(3):229-40.
AUTORES
/ AUTHORS: - Vial T; Descotes J
INSTITUCIÓN
/ INSTITUTION: - Lyon Poison Centre and Pharmacovigilance
Unit, Unit 5 Place d’Arsonval, Hopital Edouard Herriot, 69437 Lyon cedex 03,
France. thierry.vial@chu-lyon.fr
RESUMEN
/ SUMMARY: - Among the many adverse effects induced by
immunosuppressive drugs, cancers are a major cause of morbidity and mortality.
This review is based on the most recent clinical data. Epidemiological studies
and cancer registries have consistently shown an increased risk of malignancies
in transplant patients although the calculated risk (4-500-fold increase)
differs markedly between studies essentially because of differences in
methodologies and selection of patients. Skin and lip cancers, lymphomas and
Kaposi’s sarcomas are the main types of cancer in these patients. A number of
risk factors have been identified, such as latent viral infections, the
treatment regimen and the level of immunosuppression. The increasing use of
immunosuppressive drugs in nontransplant patients is useful to delineate more
accurately the consequences of mild-to-moderate immunosuppression. N. Ref:: 41
----------------------------------------------------
[125]
TÍTULO / TITLE: - Squamous cell carcinoma
of the head and neck in solid organ transplant recipients.
REVISTA
/ JOURNAL: - Head Neck 2002 Apr;24(4):319-25.
●●
Enlace al texto completo (gratuito o de pago) 1002/hed.10055 [pii]
AUTORES
/ AUTHORS: - Preciado DA; Matas A; Adams GL
INSTITUCIÓN
/ INSTITUTION: - Department of Otolaryngology-Head and Neck
Surgery, University of Minnesota, Fairview University Medical Center, MMC 396,
420 Delaware Street SE, Minneapolis, MN 55455, USA. preci001@tc.umn.edu
RESUMEN
/ SUMMARY: - BACKGROUND: The increased incidence of
cancer after solid organ transplantation is well established in the literature,
yet outcome studies in this population are rare. Excluding skin cancers,
squamous cell carcinomas make up most head and neck cancers in transplant
recipients. METHODS: At our institution, of 5300 solid organ transplant
recipients, 34 have had head and neck cancer develop. We reviewed the records
of the 23 recipients whose cancer was treated here. RESULTS: Only 6 of the 23
recipients were alive at the time of our chart review. Of these, three had
already survived 5 years. The 10 recipients diagnosed early (stage I or II) had
significantly longer survival after cancer diagnosis than the 13 diagnosed at
an advanced stage (stage III or IV) (96.0 mo vs 9.0 mo, p <.001). In all, 14
(60.8%) of the 23 recipients died of cancer within 2 years after diagnosis, 12
(50.2%) within 12 months. The sum of the daily doses of immunosuppressive drugs
at cancer diagnosis was significantly greater for recipients who died within 2
years (p =.02). Furthermore, the difference in average doses of both prednisone
(p =.001) and azathioprine (p =.028) was also significantly greater for those
who died within 2 years. The average dose of cyclosporine was also greater, but
this difference did not reach statistical significance (p =.18). The average
dose of prednisone was significantly lower for recipients diagnosed early (p
=.001). This correlation between high immunosuppressive drug doses and worse
outcome has not been shown previously. CONCLUSIONS: Solid organ transplant
recipients who are diagnosed with advanced head and neck cancer while receiving
high doses of immunosuppressive drugs fare extremely poorly. High doses of
immunosuppressive drugs, most notably prednisone, correlate significantly with
advanced diagnosis of head and neck cancer and earlier death. N. Ref:: 30
----------------------------------------------------
[126]
TÍTULO / TITLE: - Liver biopsy, viral
kinetics, and the impact of viremia on severity of hepatitis C virus
recurrence.
REVISTA
/ JOURNAL: - Liver Transpl 2003 Nov;9(11):S58-62.
●●
Enlace al texto completo (gratuito o de pago) 1053/jlts.2003.50245
AUTORES
/ AUTHORS: - Charlton M
INSTITUCIÓN
/ INSTITUTION: - Division of Gastroenterology and
Hepatology, Mayo Clinic and Foundation, Rochester, MN 55905, USA. charlton.michael@mayo.edu
RESUMEN
/ SUMMARY: - 1. Nearly all recipients who are
chronically infected with hepatitis C virus (HCV) at the time of liver
transplantation will have HCV RNA detectable postoperatively. 2. HCV
replication can begin as early as the first postoperative week. 3. HCV levels
fall significantly during the anhepatic phase of liver transplantation and
continue to fall during the first 12-24 hours posttransplantation. 4. Serum HCV
RNA levels typically increase rapidly from the second week posttransplantation
and peak by the fourth postoperative month. HCV RNA levels at one year
posttransplantation are 10-20 fold greater than pretransplant levels. 5. Corticosteroid
treatment for acute cellular rejection is associated with large increases in
HCV RNA levels. 6. HCV RNA levels do not appear to vary with choice of
calcineurin inhibitor. 7. Early HCV RNA levels are predictive of subsequent
histological severity of recurrence. 8. A correlation between early levels of
viremia and subsequent allograft injury suggests that initiation of antiviral
therapy early in the posttransplant course might be desirable. N. Ref:: 31
----------------------------------------------------
[127]
TÍTULO / TITLE: - An alternative
mechanism for the immunosuppressive effect of transfusion.
REVISTA
/ JOURNAL: - Vox Sang 2002 Aug;83 Suppl 1:417-9.
AUTORES
/ AUTHORS: - Dzik WH; Mincheff M; Puppo F
INSTITUCIÓN
/ INSTITUTION: - Blood Transfusion Service, J-224,
Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. sdzik@partners.org N. Ref:: 15
----------------------------------------------------
[128]
TÍTULO / TITLE: - Uraemic pruritus—new
perspectives and insights from recent trials.
REVISTA
/ JOURNAL: - Nephrol Dial Transplant. Acceso gratuito
al texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://ndt.oupjournals.org/
●●
Cita: Nephrology Dialysis Transplantation: <> 2002 Sep;17(9):1558-63.
AUTORES
/ AUTHORS: - Mettang T; Pauli-Magnus C; Alscher DM
INSTITUCIÓN
/ INSTITUTION: - Robert-Bosch-Hospital Stuttgart,
Department of Internal Medicine, Division of General Internal Medicine and
Nephrology, Stuttgart, Germany. Thomas.Mettang@rbk.de N. Ref:: 41
----------------------------------------------------
[129]
TÍTULO / TITLE: - Single-agent
immunosuppression after liver transplantation: what is possible?
REVISTA
/ JOURNAL: - Drugs 2002;62(11):1587-97.
AUTORES
/ AUTHORS: - Raimondo ML; Burroughs AK
INSTITUCIÓN
/ INSTITUTION: - Liver Transplantation and Hepato-Biliary
Medicine, Royal Free Hospital, Hampstead, London, UK.
RESUMEN
/ SUMMARY: - Orthotopic liver transplantation is a life
saving and life enhancing procedure. The development of immunosuppressive drugs
has contributed to the high rate of success in terms of both patient and graft
survival. However, the considerable adverse effects of these therapies are
affecting long-term outcomes of transplant recipients. Complications related to
immunosuppression are responsible for the majority of deaths in patients
surviving more than 1 year. Therefore, the search for an optimal
immunosuppressive regimen has become of paramount importance. The liver has
proved to be an ‘immunologically privileged’ organ, capable in several animal
models to be accepted as an allograft without any intervention on the immune
system of the recipient. In some human liver allografts acceptance of the new
organ is recognised after withdrawal of immunosuppressants, but prior
identification of such individuals is not yet possible, thus negating this
management option. Graft-recipient interaction is peculiar in liver
transplantation: acute cellular rejection does not always need to be treated,
and if it is not severe, appears to be associated with a better survival of
both patient and graft. In the last decade there has been an evolution of
immunosuppressive protocols, driven by empirical observation and a deeper
understanding of immunological events after transplant. However, most
modifications have been made because of the necessity to reduce long-term drug
related morbidity and mortality. Withdrawal of corticosteroids has proven to be
safely achievable in most patients, with no deleterious effects on patient or
graft survival but with a great benefit in terms of reduction of incidence of
metabolic and cardiovascular complications. Long-term ‘steroid-free’ regimens
are therefore now widely used. Patients with stable graft function can be
easily maintained using a single drug usually after 6 or 12 months and usually
with a calcineurin inhibitor. The more evolved step of using monotherapy ab
initio has also proven to be effective in a few studies and needs to be
explored further. In the future new strategies will be designed to help the
development of tolerance of the allograft, selectively stimulating instead of
suppressing the immune reaction of the recipient. N. Ref:: 51
----------------------------------------------------
[130]
TÍTULO / TITLE: - Induction of
donor-specific tolerance in rat hind-limb allografts under antilymphocyte serum
and cyclosporine A protocol.
REVISTA
/ JOURNAL: - J Hand Surg [Am] 2002 Nov;27(6):1095-103.
●●
Enlace al texto completo (gratuito o de pago) 1053/jhsu.2002.36524
AUTORES
/ AUTHORS: - Siemionow M; Oke R; Ozer K; Izycki D;
Prajapati R
INSTITUCIÓN
/ INSTITUTION: - Department of Plastic Surgery,
Microsurgery Research, The Cleveland Clinic Foundation, Cleveland, OH 44195,
USA.
RESUMEN
/ SUMMARY: - Composite tissue allograft (CTA)
transplantation became a clinical reality despite major side effects associated
with the administration of chronic immunosuppression. Development of new
treatment modalities eliminating life-long immunosuppression is essential for the
future of CTA transplantation. In this study, combined use of cyclosporine A
(CsA) and antilymphocyte serum (ALS) was tested for the potential to induce
tolerance in the rat hind-limb allograft recipients across a major
histocompatibility (MHC) barrier (Lewis-Brown-Norway [LBN, RT1(l+n)] to Lewis
[LEW, RT1(l)] rats). Thirty transplantations were performed in 5 experimental
groups. Animals received CsA and ALS 12 hours before surgery for 21 days
thereafter. Although the allograft controls rejected their limbs at day 7
combined treatment of CsA and ALS resulted in indefinite survival (over 420 d)
in all allograft recipients. Long-term survivors showed 35% to 42% of
donor-specific chimerism in the peripheral blood. Clinical tolerance was
confirmed by acceptance of the donor-specific skin grafts and immunocompetence
was confirmed by rejection of the third-party grafts. Mixed lymphocyte reaction
revealed suppressed response against donor-type antigens and increased response
to third-party antigens. Donor-specific tolerance across MHC barrier was
induced in CTA allografts under 21 days protocol of ALS/CsA.
----------------------------------------------------
[131]
TÍTULO / TITLE: - Statins and renal
function.
REVISTA
/ JOURNAL: - Angiology 2002 Sep-Oct;53(5):493-502.
AUTORES
/ AUTHORS: - Elisaf M; Mikhailidis DP
INSTITUCIÓN
/ INSTITUTION: - Department of Internal Medicine, Medical
School, University of Ioannina, Greece.
RESUMEN
/ SUMMARY: - Renal disease is often associated with an
increased risk of vascular events. Moreover, an accelerated form of
atherosclerosis commonly occurs in these patients. The reasons for these
associations are not clearly defined but include the widespread presence of
several established risk factors (eg, dyslipidemia, hypertension, and
diabetes). Other predictors of atherosclerotic disease may also be abnormally
elevated (eg, homocysteine, fibrinogen, and lipoprotein a). In addition, there
is evidence that impaired renal function per se predicts vascular risk. Despite
this high-risk background, the potential benefit of treatment with statins has
not been widely investigated in these patients. The present review considers
the evidence (experimental and clinical) that statins exert beneficial effects
in patients with different types of renal disease. This includes improved renal
function, decreased microalbuminuria, and a fall in blood pressure. Statins may
also improve renal allograft survival. The potential mechanisms mediating these
effects are considered. The interactions between statins and several risk
factors that may be present in patients with impaired renal function are also
considered. There is an urgent need to define the role of statins in these
high-risk patients. Which is the statin of choice? This question is relevant because
impaired renal function can interfere with statin pharmacokinetics.
Furthermore, other drugs administered to these patients may cause serious
interactions with statins. N.
Ref:: 113
----------------------------------------------------
[132]
TÍTULO / TITLE: - Causes of late renal
allograft loss: chronic allograft dysfunction, death, and other factors.
REVISTA
/ JOURNAL: - Transplantation 2001 Jun 15;71(11
Suppl):SS5-9.
AUTORES
/ AUTHORS: - Kreis HA; Ponticelli C
INSTITUCIÓN
/ INSTITUTION: - Hjpital Necker, University of Paris,
France.
RESUMEN
/ SUMMARY: - CAN and patient death with allograft
function are the 2 major causes of renal allograft loss after the first year,
accounting for 80% or more of cases. According to current estimates from the
United Network for Organ Sharing (UNOS), the half-lives for renal allografts
performed in 1995 and 1996 from living and cadaveric donors are 15.3 and 10.4
years, respectively (2). Consequently, much attention has been focused on
better understanding the causes of CAN and patient death with a functioning
allograft in an attempt to improve long-term renal allograft outcomes. Although
the pathogenesis of CAN is not completely understood, we know that CAN involves
alloantigen-dependent and alloantigen-independent factors that combine to
produce chronic deterioration of renal allograft function. CVD is the most
frequent cause of death in renal transplant recipients, and we need to address
its well-established risk factors in that population. Among other improvements,
changes in current immunosuppressive protocols may increase long-term renal
allograft survival and function by decreasing both the risk of CAN and the risk
of CVD. N. Ref:: 50
----------------------------------------------------
[133]
TÍTULO / TITLE: - Sirolimus (Rapamune) in
renal transplantation.
REVISTA
/ JOURNAL: - Curr Opin Nephrol Hypertens 2002
Nov;11(6):603-7.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.mnh.0000040045.55337.97
AUTORES
/ AUTHORS: - Johnson RW
INSTITUCIÓN
/ INSTITUTION: - Manchester Postgraduate Health Sciences
Centre, Manchester Royal Infirmary, Manchester.
RESUMEN
/ SUMMARY: - There has been a necessary change in
attitude to transplantation; there is much less concern with short-term outcome
and more concern with long-term kidney function, overall health and quality of
life. Nephrotoxicity is an invariable consequence of long-term treatment with
calcineurin antagonists and it is one of the most underestimated causes of late
graft loss; it has been reported as a serious threat to both patient and graft
survival following heart, liver and bone marrow transplantation. Sirolimus has
been shown in many recent studies to be of great value in allowing patients to
be weaned from cyclosporine with excellent patient and graft survival at 24
months a significant improvement in renal function with resolution of hirsutism
and gum hyperplasia. Patients maintained on the combined regime of cyclosporine
and sirolimus had significantly higher blood pressure, much more cyclosporine
nephrotoxicity and hyperuricaemia at 12 months. The experimental studies have
found cyclosporine and sirolimus potentiate with each other’s good and adverse
effects. Cyclosporine therefore augments hyperlipidaemia caused by sirolimus,
and sirolimus augments nephrotoxicity caused by cyclosporine. The results of
these studies indicate that sirolimus is a suitable replacement for
cyclosporine or tacrolimus for long-term maintenance therapy. By contrast the
use of sirolimus in combination with cyclosporine results in potentiation of
side effects. The principal disadvantages being increased cyclosporine
associated nephrotoxicity and sirolimus associated hyperlipidaemia N. Ref:: 32
----------------------------------------------------
[134]
TÍTULO / TITLE: - Immunosuppressive
effect of pregnancy on autoimmune hepatitis: a case report and review of
literature.
REVISTA
/ JOURNAL: - Eur J Obstet Gynecol Reprod Biol 2002 Feb
10;101(1):91-2.
AUTORES
/ AUTHORS: - Malhotra B; Malhotra N; Deka D; Takkar D
INSTITUCIÓN
/ INSTITUTION: - Department of Obstetrics and Gynecology,
All India Institute of Medical Sciences, New Delhi, India. bhawnams@hotmail.com
RESUMEN
/ SUMMARY: - We report a case of autoimmune hepatitis
with suppressed disease activity during pregnancy and relapse in puerperium.
This is only the second report of such pregnancy-induced remission. N. Ref:: 7
----------------------------------------------------
[135]
TÍTULO / TITLE: - An induction versus
no-induction protocol in anticalcineurin-based immunosuppression using very
low-dose steroids.
REVISTA
/ JOURNAL: - Transplant Proc 2001 Jun;33(4
Suppl):3S-10S.
AUTORES
/ AUTHORS: - Charpentier B
INSTITUCIÓN
/ INSTITUTION: - University Hospital of Bicetre, Le
Kremlin-Bicetre, France.
----------------------------------------------------
[136]
TÍTULO / TITLE: - Polyomavirus BK
nephropathy: a (re-)emerging complication in renal transplantation.
REVISTA
/ JOURNAL: - Am J Transplant 2002 Jan;2(1):25-30.
AUTORES
/ AUTHORS: - Hirsch HH
INSTITUCIÓN
/ INSTITUTION: - Department of Internal Medicine,
University of Basel, Switzerland. hans.hirsch@unibas.ch
RESUMEN
/ SUMMARY: - Persisting polyomavirus replication is now
widely recognized as a (re-)emerging cause of renal allograft dysfunction. Up
to 5% of renal allograft recipients can be affected about 40weeks (range 6-150)
post-transplantation. Progression to irreversible failure of the allograft has
been observed in up to 45% of all cases. The BK virus strain is involved in the
majority of the cases. Risk factors may include treatment of rejection episodes
and increasing viral replication under potent immunosuppressive drugs such as
tacrolimus, sirolimus or mycophenolate. The diagnosis requires the histological
demonstration of nuclear polyomavirus inclusions in affected tubular epithelial
cells. Interstitial inflammatory infiltrates and fibrosis become more prominent
in the persisting disease and may be difficult to distinguish from (coexisting)
rejection. Detection of polyomavirus-inclusion bearing cells (‘decoy cells’) in
the urine and quantification of BK virus DNA in the plasma have been proposed
as surrogate markers for polyomavirus replication and allograft disease,
respectively. Antiviral treatment is not yet established; however, reports of
treatment with cidofovir are encouraging. Current management aims at the
judicious modification and/or reduction of immunosuppression which, in view of
preceding or concurrent rejection, is not without risk. N. Ref:: 51
----------------------------------------------------
[137]
TÍTULO / TITLE: - Immunosuppressive
therapy and post-transplantation diarrhea.
REVISTA
/ JOURNAL: - Clin Transplant 2001;15 Suppl 4:23-8.
AUTORES
/ AUTHORS: - Pescovitz MD; Navarro MT
INSTITUCIÓN
/ INSTITUTION: - Department of Surgery, Indiana University,
Indianapolis, USA. mpescov@iupui.edu
RESUMEN
/ SUMMARY: - Gastrointestinal complications, including
diarrhea, are among the anticipated adverse events secondary to
immunosuppression. The reported overall rate of diarrhea may be affected by
drug-specific effects, dose-response effects, interactions with other
medications, drug formulation, the length of study follow-up, reporting bias
and population characteristics such as ethnicity and baseline disease,
including transplant organ type. The true incidence of diarrhea is often
difficult to assess from the numerous published clinical trials. A number of
deficiencies, including self-reporting, interstudy comparisons, lack of
blinding, concomitant medications and a general lack of standardization and
quantification of diarrhea may greatly obscure comparisons among the different
immunosuppressive medications. This review considers each of these factors in
assessing the overall incidence of post-transplantation diarrhea for the
various immunosuppressive medications currently in use. N. Ref:: 15
----------------------------------------------------
[138]
TÍTULO / TITLE: - Nonmyeloablative
hematopoietic cell transplantation. Replacing high-dose cytotoxic therapy by
the graft-versus-tumor effect.
REVISTA
/ JOURNAL: - Ann N Y Acad Sci 2001 Jun;938:328-37; discussion
337-9.
AUTORES
/ AUTHORS: - Feinstein L; Sandmaier B; Maloney D;
McSweeney PA; Maris M; Flowers C; Radich J; Little MT; Nash RA; Chauncey T;
Woolfrey A; Georges G; Kiem HP; Zaucha JM; Blume KG; Shizuru J; Niederwieser D;
Storb R
INSTITUCIÓN
/ INSTITUTION: - Fred Hutchinson Cancer Research Center,
1100 Fairview Avenue N., D1-100, P.O. Box 19024, Seattle, Washington
98109-1024, USA. lfeinste@fhcrc.org
RESUMEN
/ SUMMARY: - Conventional allografting produces
considerable regimen-related toxicities that generally limit this treatment to
patients younger than 55 years and in otherwise good medical condition. T
cell-mediated graft-versus-tumor (GVT) effects are known to play an important
role in the elimination of malignant disease after allotransplants. A minimally
myelosuppressive regimen that relies on immunosuppression for allogeneic
engraftment was developed to reduce toxicities while optimizing GVT effects.
Pre-transplant total-body irradiation (200 cGy) followed by post-transplant
immunosuppression with cyclosporine (CSP) and mycophenolate mofetil (MMF)
permitted human leukocyte antigen (HLA)-matched sibling donor hematopoietic
cell engraftment in 82% of patients (n = 55) without prior high-dose therapy.
The addition of fludarabine (90 mg/m2) facilitated engraftment in all 28
subsequent patients. Overall, fatal progression of underlying disease occurred
in 20% of patients after transplant. Non-relapse mortality occurred in 11% of
patients. Toxicities were low. Grade 2-4 acute graft-versus-host disease (GVHD)
associated with primary engraftment developed in 47% of patients, and was
readily controlled in all but two patients. Donor lymphocyte infusions (DLI)
were not very effective at converting a low degree of mixed donor/host
chimerism to full donor chimerism; however, the addition of fludarabine reduced
the need for DLI. With a median follow-up of 244 days, 68% of patients were
alive, with 42% of patients in complete remission, including molecular remissions.
Remissions occurred gradually over periods of weeks to a year. If long-term
efficacy is demonstrated, such a strategy would expand treatment options for
patients who would otherwise be excluded from conventional allografting. N. Ref:: 51
----------------------------------------------------
[139]
TÍTULO / TITLE: - Cyclosporine
nephrotoxicity.
REVISTA
/ JOURNAL: - Semin Nephrol 2003 Sep;23(5):465-76.
AUTORES
/ AUTHORS: - Burdmann EA; Andoh TF; Yu L; Bennett WM
INSTITUCIÓN
/ INSTITUTION: - Division of Nephrology, Sao Jose do Rio
Preto Medical School, Sao Jose do Rio Preto, Brazil. burdmann@famerp.br
RESUMEN
/ SUMMARY: - After more than 20 years of cyclosporine
use its nephrotoxicity remains a significant clinical problem.
Cyclosporine-induced renal injury has been described in solid organs recipients
and in patients treated for autoimmune diseases. It is manifested in 2 distinct
and well characterized forms, acute nephrotoxicity and chronic nephrotoxicity. This
communication reviews the current literature analyzing the available data about
the pathogenesis and mechanisms of acute and chronic cyclosporine-induced
nephrotoxicity. A working hypothesis for the possible mechanisms of chronic
cyclosporine nephrotoxicity will be provided.
N. Ref:: 89
----------------------------------------------------
[140]
TÍTULO / TITLE: - Induction versus
non-induction protocols in anti-calcineurin-based immunosuppression.
REVISTA
/ JOURNAL: - Transplant Proc 2001 Nov-Dec;33(7-8):3334-6.
AUTORES
/ AUTHORS: - Charpentier B
INSTITUCIÓN
/ INSTITUTION: - Service de Nephrologie, University
Hospital of Bicetre, Bicetre, France.
----------------------------------------------------
[141]
TÍTULO / TITLE: - Intestinal and
multivisceral transplantation.
REVISTA
/ JOURNAL: - World J Surg 2002 Feb;26(2):226-37. Epub
2001 Dec 21.
●●
Enlace al texto completo (gratuito o de pago) 1007/s00268-001-0210-5
AUTORES
/ AUTHORS: - Kato T; Ruiz P; Thompson JF; Eskind LB;
Weppler D; Khan FA; Pinna AD; Nery JR; Tzakis AG
INSTITUCIÓN
/ INSTITUTION: - Division of Transplantation, University of
Miami School of Medicine, Miami, Florida 33136, USA.
RESUMEN
/ SUMMARY: - Intestinal transplantation has been
gradually instituted in the management of intestinal failure. More than 200
cases including isolated intestinal transplant, liver/intestinal transplant,
and multivisceral transplant have been performed worldwide,with 1-year graft
and patient survival rates of 66% and 54%,respectively. Indications for the
procedure include short bowel syndrome and functional abnormalities secondary
to a variety of diseases or conditions. Tacrolimus-based immunosuppression
regimens have been used universally with improved outcomes. The major
contributors to the morbidity and mortality include rejection,infection, and
technical complications. Of those, control of rejection remains the most
difficult dilemma and it will be the key to improved patient and graft survival. N. Ref:: 60
----------------------------------------------------
[142]
TÍTULO / TITLE: - Nephrotoxicity of
immunosuppressive drugs: new insight and preventive strategies.
REVISTA
/ JOURNAL: - Curr Opin Crit Care 2001 Dec;7(6):384-9.
AUTORES
/ AUTHORS: - Olyaei AJ; de Mattos AM; Bennett WM
INSTITUCIÓN
/ INSTITUTION: - Division of Nephrology, Hypertension and
Clinical Pharmacology, Oregon Health Sciences University and Solid Organ and
Cellular Transplantation, Legacy Good Samaritan Hospital, Portland, Oregon
97201, USA. olyaeia@ohsu.edu
RESUMEN
/ SUMMARY: - Cyclosporine and tacrolimus reduce
allograft rejection, improve allograft half-life and patient survival.
Ironically, the nephrotoxicity of these agents may adversely affect allograft
survival in renal transplant recipients or cause end-stage renal diseases in
other solid organ and bone marrow transplant recipients. Acute dose-dependent
and chronic non-dose-dependent nephrotoxicity has been reported in both
transplant recipients and patients with autoimmune disorders. Preliminary
evidence suggests that drug therapeutic monitoring has little value in the
diagnosis or management of nephrotoxicity associated with calcineurin
inhibitors. Although the exact mechanism of nephrotoxicity is not fully
understood, several factors have been implicated in the pathogenesis of
immunosuppressive-induced nephrotoxicity. Renal and systemic vasoconstriction,
increased release of endothelin-1, decreased production of nitric acid and
increased expression of TGF-beta are the major adverse pathophysiologic
abnormalities of these agents. Reducing the dose of a calcineurin inhibitor, or
using protocols without calcineurin inhibition may ultimately minimize the risk
of drug toxicity and improve allograft and patient survival. New experiences
with non-nephrotoxic agents and protocols including mycophenolate and sirolimus
allow for early calcineurin inhibitor reduction or elimination without
increasing the risk of allograft rejection.
N. Ref:: 55
----------------------------------------------------
[143]
TÍTULO / TITLE: - Rejection-free protocol
using sirolimus-tacrolimus combination for pediatric renal transplant
recipients.
REVISTA
/ JOURNAL: - Transplant Proc 2002 Aug;34(5):1942-3.
AUTORES
/ AUTHORS: - El-Sabrout R; Weiss R; Butt F; Delaney V;
Qadir M; Hanson P; Butt K
INSTITUCIÓN
/ INSTITUTION: - Departments of Transplantation/Vascular
Surgery, New York Medical College, Valhalla, New York, USA.
----------------------------------------------------
[144]
TÍTULO / TITLE: - In utero exposure to
immunosuppressive drugs: experimental and clinical studies.
REVISTA
/ JOURNAL: - Pediatr Nephrol 2002 Feb;17(2):121-30.
AUTORES
/ AUTHORS: - Tendron A; Gouyon JB; Decramer S
INSTITUCIÓN
/ INSTITUTION: - Hopital d’Enfants, Service de
Neonatologie, 10 boulevard Mal de Lattre de Tassigny, 21034 Dijon Cedex,
France. anais.tendron@planetb.fr
RESUMEN
/ SUMMARY: - Over the last few decades, the number of
pregnant women under immunosuppressive (IS) therapy following transplantation
or autoimmune diseases has increased. At first, IS drugs, including prednisone,
azathioprine, and cyclosporine A were used, but now new molecules such as
tacrolimus and mycophenolate mofetil have appeared. These IS drugs cross the
placental barrier and enter into the fetal circulation, which poses a risk for
fetal development. Experimental data have shown that IS drugs often have
deleterious effects on fetuses, while human data have reported an increased
rate of abortion, prematurity, intrauterine growth retardation (IUGR), and low
birth weight, without significant increases in malformation rates. However,
only limited information is available about the newly used molecules. Although
fetal and neonatal data are reassuring, long-term effects of IS drugs on
fertility, immune response and renal function, as well as the consequences of
prematurity and IUGR, should be monitored.
N. Ref:: 78
----------------------------------------------------
[145]
TÍTULO / TITLE: - Comparative
tolerability of systemic treatments for plaque-type psoriasis.
REVISTA
/ JOURNAL: - Drug Saf. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.csmwm.org/
●●
Cita: Drug Safety: <> 2002;25(13):913-27.
AUTORES
/ AUTHORS: - McClure SL; Valentine J; Gordon KB
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology, Northwestern
University Medical School, Chicago, Illinois 60611, USA.
RESUMEN
/ SUMMARY: - Psoriasis is a chronic, debilitating skin
condition that affects millions of people and is attributed to both genetic and
environmental factors. Topical therapy is generally considered to be the
first-line treatment of psoriasis. However, many patients do not respond to
topical therapy or have disease so extensive that topical therapy is not
practical. For these patients, systemic therapy is indicated. Presently, there
are four available systemic treatments, psoralen with ultraviolet A (PUVA),
methotrexate, oral retinoids (acitretin), and cyclosporin. Unfortunately, all
of these treatments have significant potential adverse effects. PUVA may
acutely cause nausea, pruritis and sunburn. More chronic and concerning is the
development of PUVA lentigines, ocular complications and skin cancer.
Non-melanoma skin cancer has been directly linked to PUVA; however, the
association with melonoma is more elusive. Methotrexate use most notably
carries the risk of hepatic fibrosis and cirrhosis, which is not always evident
on liver function tests. Other more rare, but potentially life-threatening
adverse effects include pancytopenia, lymphoproliferative disorders and acute
pneumonitis. The addition of folic acid may help to reduce the risk of increasing
liver enzymes and haematological toxicity seen in those taking methotrexate.
Both methotrexate and oral retinoids are teratogenic and should never be used
in pregnancy. Oral retinoids are probably the least effective available
systemic medication for the treatment of plaque psoriasis. The effects are
improved with the addition of other systemic therapies. Acitretin has replaced
the formerly used etretinate primarily because of the significantly shorter
half-life. The adverse effects are generally mild and reversible, making the
drug fairly safe for long-term use. The most commonly seen adverse effects
include elevated serum lipids, generalised xerosis and alopecia. Bony
abnormalities, while somewhat controversial, have also been described and
include diffuse idiopathic skeletal hyperostosis, skeletal calcifications and
osteoporosis. Cyclosporin is the most recently approved systemic medication for
plaque psoriasis. The nephrotoxicity associated with the use of cyclosporin can
be minimised when used in lower doses and for a limited duration. Hypertension
is usually mild and can be seen in up to about one-third of patients receiving
long-term therapy. Cutaneous and internal malignancies have also been reported
with cyclosporin and tend to be correlated with duration of treatment. In this
review, we will examine the potential adverse effects with these US Food and
Drug Administration-approved treatments in adults, with specific emphasis on
the controversies that surround long-term therapy with these agents and their
cumulative adverse effects. N.
Ref:: 151
----------------------------------------------------
[146]
TÍTULO / TITLE: - The limitations of
calcineurin and mTOR inhibitors: new directions for immunosuppressive
strategies.
REVISTA
/ JOURNAL: - Transplant Proc 2002 Feb;34(1):130-3.
AUTORES
/ AUTHORS: - Kahan BD
INSTITUCIÓN
/ INSTITUTION: - Division of Organ Transplantation,
Department of Surgery, The University of Texas Medical School, Houston, Texas
77030, USA. N. Ref:: 76
----------------------------------------------------
[147]
TÍTULO / TITLE: - Cardiovascular
toxicities of immunosuppressive agents.
REVISTA
/ JOURNAL: - Am J Transplant 2002 Oct;2(9):807-18.
AUTORES
/ AUTHORS: - Miller LW
INSTITUCIÓN
/ INSTITUTION: - Cardiovascular Division, University of
Minnesota, Minneapolis, USA. mille278@tc.umn.edu
RESUMEN
/ SUMMARY: - Cardiovascular disease is one of the major
causes of morbidity and mortality following solid organ transplantation. Many
of the current immunosuppressive drugs are associated with an increase of one
or more risk factors for the development of atherosclerosis. This review
compares the mechanism by which individual immunosuppressive agents may impact
on these risk factors and the differential contribution of cyclosporine,
tacrolimus, mycophenolate, azathioprine, and Rapamycin to these individual risk
factors. Attention to the potential cardiovascular toxicities of individual
immunosuppressive agents may help design strategies for maintenance of
immunosuppression tailored to individual patients. N. Ref:: 139
----------------------------------------------------
[148]
TÍTULO / TITLE: - Can we prevent in-stent
restenosis?
REVISTA
/ JOURNAL: - Curr Opin Cardiol 2002 Sep;17(5):518-25.
AUTORES
/ AUTHORS: - Garza L; Aude YW; Saucedo JF
INSTITUCIÓN
/ INSTITUTION: - Division of Cardiovascular Medicine,
University of Arkansas for Medical Sciences, Little Rock, 72205, USA. garzaluis@uams.edu
RESUMEN
/ SUMMARY: - Nowadays stent placement has replaced
balloon angioplasty as the most commonly performed percutaneous coronary
interventional procedure, mainly because of its better acute and chronic
outcome. As a result, in-stent restenosis (ISR) has become a widespread
problem. The incidence of ISR varies from 10% to 50% and depends on the absence
or presence of several risk factors, such as small vessel size, longer lesions,
and diabetes. Intravascular ultrasound studies have demonstrated that ISR is mainly
caused by neointimal proliferation; consequently, this pathologic process has
become the target of many preventive and therapeutic approaches. This article
provides an overview of such management strategies, highlighting the rather
disappointing experiences with mechanical and systemic drug therapies; the
relative merits and disadvantages of intracoronary radiation; and the exciting
yet realistic promise, embodied by the recent advancements in drug-eluting
stent technology, of potentially eradicating ISR in the near future. N. Ref:: 90
----------------------------------------------------
[149]
TÍTULO / TITLE: - Intracranial hemorrhage
in neuro-Behcet’s syndrome.
REVISTA
/ JOURNAL: - Intern Med 2002 Sep;41(9):692-5.
AUTORES
/ AUTHORS: - Kikuchi S; Niino M; Shinpo K; Terae S;
Tashiro K
INSTITUCIÓN
/ INSTITUTION: - Department of Neurology, Hokkaido
University Graduate School of Medicine, Sapporo.
RESUMEN
/ SUMMARY: - OBJECTIVE: Most cerebrovascular
disturbances in Behcet’s syndrome are occlusive in nature, while hemorrhage is
rare. In this paper, we report three cases of neuro-Behcet’s syndrome
presenting with intracerebral hemorrhaging, and discuss the possible causes as
they relate to cyclosporine treatment. PATIENTS: Three cases of neuro-Behcet’s
syndrome presented with intracranial hemorrhage. One patient had been taking
cyclosporine, and the other two patients had never taking cyclosporine.
RESULTS: Together with previous reports, these cases suggest that there are two
types of intracranial hemorrhage in neuro-Behcet’s syndrome. One type occurs in
the center of a lesion and during the acute phase of the disease, while the
other occurs in the peripheral lesion and during the subacute phase.
CONCLUSIONS: It appears that the intracranial hemorrhages in neuro-Behcet’s
syndrome can be divided into two groups. It is possible that the vascular
pathologies caused by Behcet’s syndrome and by cyclosporine conspire to induce
CNS hemorrhaging in some cases. N.
Ref:: 19
----------------------------------------------------
[150]
TÍTULO / TITLE: - Drug-nutrient
interactions in transplant recipients.
REVISTA
/ JOURNAL: - JPEN J Parenter Enteral Nutr 2001
May-Jun;25(3):132-41.
AUTORES
/ AUTHORS: - Chan LN
INSTITUCIÓN
/ INSTITUTION: - Department of Pharmacy Practice &
Medicine, Colleges of Pharmacy and Medicine, University of Illinois at Chicago,
60612, USA. neander@uic.edu
RESUMEN
/ SUMMARY: - Drug-nutrient interaction refers to an
alteration of kinetics or dynamics of a drug or a nutritional element, or a
compromise in nutritional status as a result of the addition of a drug. The
potentials for drug-nutrient interaction increase with the number of drugs
taken by the patient. Organ transplant recipients are therefore at high risk
for drug-nutrient interactions because multiple medications are used to manage
graft rejection, opportunistic infections, and other associated complications.
Unrecognized or unmanaged drug-nutrient interactions in this patient population
can have an adverse impact on their outcomes. This paper reviews the importance
of recognizing drug-nutrient interaction when using cyclosporine-based
regimens. N. Ref:: 74
----------------------------------------------------
[151]
- Castellano -
TÍTULO / TITLE:Colitis ulcerosa asociada a purpura
trombocitopenica idiopatica. Ulcerative colitis associated with idiopathic
thrombocytopenic purpura.
REVISTA
/ JOURNAL: - Gastroenterol Hepatol. 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: Gastroenterología & Hepatología: <> 2003 Nov;26(9):545-8.
AUTORES
/ AUTHORS: - Puebla Maestu A; Martin-Lorente JL;
Lopez-Morante A; Garcia-Moran S; Yuguero del Moral L; Arauzo Gonzalez A
INSTITUCIÓN
/ INSTITUTION: - Seccion de Aparato Digestivo, Hospital
General Yague, Burgos, España. aidapuebla@hotmail.com
RESUMEN
/ SUMMARY: - Multiple hematological anomalies have been
described in association with chronic inflammatory bowel disease. Idiopathic
thrombocytopenic purpura is an autoimmune disease characterized by the presence
of isolated thrombopenia with a normal or increased number of megakaryocytes in
bone marrow and absence of splenomegaly. Several case reports of idiopathic
thrombocytopenic purpura associated with chronic inflammatory bowel disease,
mostly ulcerative colitis, have been published in the literature. The
pathogenic mechanism through which these entities are associated is unknown.
Several treatments have been used, varying from short courses of steroids to
the use of immunosuppressive agents and splenectomy, depending on the severity
of the symptoms. We describe the case of a woman with ulcerative colitis and
idiopathic thrombocytopenic purpura, in which the latter first presented when
the patient was undergoing treatment with corticosteroids and cyclosporin, one
of the therapeutic options for controlling thrombopenic purpura. Platelet deficiency
persisted despite treatment with azathioprine and colectomy, also described as
a possible curative treatment. N.
Ref:: 36
----------------------------------------------------
[152]
TÍTULO / TITLE: - Cutaneous T-cell
lymphoma in a cardiac transplant recipient.
REVISTA
/ JOURNAL: - Tex Heart Inst J. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://texasheartinstitute.org/journal.html
●●
Cita: Texas Heart Institute Journal: <> 2001;28(3):203-7.
AUTORES
/ AUTHORS: - McMullan DM; Radovaneevic B; Jackow CM;
Frazier OH; Duvic M
INSTITUCIÓN
/ INSTITUTION: - Texas Heart Institute and St Luke s
Episcopal Hospital Houston, 77225-0345, USA.
RESUMEN
/ SUMMARY: - Mycosis fungoides, an uncommon form of
cutaneous T-cell lymphoma, arises in the skin and frequently progresses to
generalized lymphadenopathy Although the cause of cutaneous T-cell lymphoma is
unknown, chronic immunosuppression may play a role. A few cases have been
reported in renal transplant recipients; however, ours appears to be the 1st
report of cutaneous T-cell lymphoma in a cardiac transplant recipient. In our
patient, cutaneous manifestations of the disease were noted less than 1 year
after transplantation. Seven years after transplantation, Sezary syndrome, a
variant form of mycosis fungoides, was diagnosed by tissue biopsy and flow
cytometry analysis. Photopheresis improved symptoms but was not well tolerated
because of hemodynamic sequelae. Psoralen and ultraviolet A therapy also
improved the patient’s skin condition, but a generalized lymphadenopathy
developed. The maintenance immunosuppressive regimen was changed from
cyclosporine (3 mg/kg/day) and azathioprine to cyclosporine (1.5 mg/kg/day) and
cyclophosphamide. Although effective in the short-term, the results of this
therapeutic strategy could not be fully evaluated because the patient died of
acute myocardial infarction. N.
Ref:: 25
----------------------------------------------------
[153]
TÍTULO / TITLE: - Long-term
immunosuppression and drug interactions.
REVISTA
/ JOURNAL: - Liver Transpl 2001 Nov;7(11 Suppl
1):S53-9.
●●
Enlace al texto completo (gratuito o de pago) 1053/jlts.2001.28512
AUTORES
/ AUTHORS: - Levy GA
INSTITUCIÓN
/ INSTITUTION: - Multi Organ Transplant Program, Toronto
General Hospital, University of Toronto, Ontario, Canada. glfgl2@attglobal.net
RESUMEN
/ SUMMARY: - 1. Early patient and graft survival are
excellent after liver transplantation. 2. The focus must be on reducing
toxicity associated with long-term immunosuppression. 3. Available new drugs
offer the potential to reduce toxicity by combination therapy or replacement of
toxic agents. 4. Individual patient immunosuppressive protocols should be
developed. 5. Drug interactions are common and the source of significant
morbidity. N. Ref:: 17
----------------------------------------------------
[154]
TÍTULO / TITLE: - Membranous
glomerulonephritis after haematopoietic cell transplantation for multiple
myeloma.
REVISTA
/ JOURNAL: - Nephron 2001 Jul;88(3):260-3.
AUTORES
/ AUTHORS: - Rossi L; Cardarelli F; Vampa ML; Buzio C;
Olivetti G
INSTITUCIÓN
/ INSTITUTION: - Dipartimenti di Clinica Medica, Nefrologia
e Scienze della Prevenzione e, Sezione di Anatomia Patologica, Universita degli
Studi, Parma, Italia.
RESUMEN
/ SUMMARY: - Renal involvement during graft-versus-host
disease following haematopoietic cell transplantation for multiple myeloma has
never been described. We report a case of a recipient who developed nephrotic
syndrome and membranous glomerulonephritis 22 months after the graft and 6
months after cyclosporine withdrawal. Symptoms resolved when immunosuppressive
therapy was reinstituted. N.
Ref:: 18
----------------------------------------------------
[155]
TÍTULO / TITLE: - Treatment of transplant
rejection: are the traditional immunosuppressants good enough?
REVISTA
/ JOURNAL: - Curr Opin Investig Drugs 2001
Mar;2(3):357-63.
AUTORES
/ AUTHORS: - Dumont FJ
INSTITUCIÓN
/ INSTITUTION: - Department Immunology & Rheumatology, Merck Research Laboratories,
Rahway, NJ 07065, USA. francis_dumont@merck.com
RESUMEN
/ SUMMARY: - Due to the improvement in the
understanding of the anti-allogenic immune response, the success of
transplantation medicine has increased rapidly over the last two decades. The
knowledge that the T-lymphocyte played an integral role in transplant
rejection, brought cyclosporine A and FK-506 to the fore as therapeutic
immunosuppressants. However, the current mainstays in transplant rejection are
not without their problems and many drug companies are exploring the
possibilities of improving the available therapies by developing drugs with
reduced toxicity, improved long-term survival and efficacy against chronic
rejection and improved immunosuppressive selectivity. The advances in the
understanding of T-cell activation and lymphocyte trafficking has highlighted
ways to improve the existing therapies and more selective immunosuppressant
targets. N. Ref:: 60
----------------------------------------------------
[156]
TÍTULO / TITLE: - Place of mycophenolate
mofetil in renal transplantation.
REVISTA
/ JOURNAL: - Transplant Proc 2001
Feb-Mar;33(1-2):997-9.
AUTORES
/ AUTHORS: - Grinyo JM
INSTITUCIÓN
/ INSTITUTION: - Hospital de Bellvitge, Barcelona,
España. N. Ref:: 23
----------------------------------------------------
[157]
TÍTULO / TITLE: - In utero exposure to
immunosuppressive drugs.
REVISTA
/ JOURNAL: - Biol Neonate 2002;81(2):73-81.
AUTORES
/ AUTHORS: - Prevot A; Martini S; Guignard JP
INSTITUCIÓN
/ INSTITUTION: - Department of Pediatrics, Pediatric
Nephrology Unit, Centre Hospitalier Universitaire Vaudois, Lausanne,
Switzerland. prevotanne@hotmail.com
RESUMEN
/ SUMMARY: - The number of pregnant women receiving
immunosuppressants for anti-rejection therapy or autoimmune diseases is increasing.
All immunosuppressive drugs cross the placenta, raising questions about the
long-term outcome of the children exposed in utero. There is no higher risk of
congenital anomalies. However, an increased incidence of prematurity,
intrauterine growth retardation (IUGR) and generally low birth weight has been
reported, as well as maternal hypertension and preeclampsia. The most frequent
neonatal complications are those associated with prematurity and IUGR, as well
as adrenal insufficiency with corticosteroids, immunological disturbances with
azathioprine and cyclosporine, and hyperkalemia with tacrolimus. The long-term
follow-up of infants exposed to immunosuppressants in utero is still limited
and experimental studies raise the question whether there could be an increased
incidence at adult age of some pathologies including renal insufficiency,
hypertension and diabetes. N.
Ref:: 58
----------------------------------------------------
[158]
TÍTULO / TITLE: - Questionable efficacy
of plasma exchange for thrombotic thrombocytopenic purpura after bone marrow
transplantation.
REVISTA
/ JOURNAL: - J Clin Apheresis 2001;16(4):169-74.
●●
Enlace al texto completo (gratuito o de pago) 1002/jca.10008 [pii]
AUTORES
/ AUTHORS: - Teruya J; Styler M; Verde S; Topolsky D;
Crilley P
INSTITUCIÓN
/ INSTITUTION: - Department of Pathology, Northwestern
University, Chicago, Illinois, USA. j-teruya@northwestern.edu
RESUMEN
/ SUMMARY: - Thrombotic thrombocytopenic purpura (TTP)
after bone marrow transplantation (BMT) is an uncommon complication presumably
associated with extensive endothelial cell damage due to Cyclosporine, total
body irradiation, or other drugs. While the majority of patients with primary
TTP, which is considered to be an autoimmune process, respond to plasma
exchange, TTP after BMT has a very poor prognosis. A total of 7 patients out of
307 patients who underwent BMT were diagnosed with TTP during 1989-1999. The
diagnosis of TTP was made based on thrombocytopenia and microhemangiopathic
hemolytic anemia characterized by an elevated LDH and the presence of
schistocytes on the peripheral blood smear. Five patients were treated with
plasma exchange (PE) using fresh frozen plasma and/or cryoprecipitate poor
plasma as replacement fluid. One patient was treated using a protein A column. One
patient did not receive plasma exchange because the 125 patient was clinically
stable and was discharged. It was hard to assess the efficacy of PE due to the
multiplicity of the patients’ clinical condition and laboratory data. At least
4 patients did not respond to PE and 2 patients were not able to be evaluated
due to multi organ failure. However, all patients died. It is not clear at this
moment if PE for patients with TTP after BMT is truly beneficial. N. Ref:: 10
----------------------------------------------------
[159]
TÍTULO / TITLE: - Immunologic targets for
currently available immunosuppressive agents: what is the optimal approach for
children?
REVISTA
/ JOURNAL: - Semin Nephrol 2001 Sep;21(5):508-20.
AUTORES
/ AUTHORS: - Sho M; Samsonov DV; Briscoe DM
INSTITUCIÓN
/ INSTITUTION: - Division of Nephrology, Department of
Medicine, Children’s Hospital and Harvard Medical School, Boston, MA 02115,
USA.
RESUMEN
/ SUMMARY: - In this review, the authors discuss
immunologic targets and events in T cells that are dysregulated by commonly
used immunosuppressive agents. These include a description of glucocortcoid
receptors as well as targets of glucocorticoids, targets of cyclosporine and
FK506, and the mammalian target of rapamycin. In addition, novel antibody-based
targets on T cells and antigen-presenting cells including the IL-2 receptor and
costimulatory molecules are described. Finally, the authors provide a rationale
for an optimal approach to immunosuppression in pediatrics. Because many of the
newer immunosuppressive agents are currently in clinical trials, the “optimal”
immunosuppressive strategy for the next decade is forthcoming. N. Ref:: 122
----------------------------------------------------
[160]
TÍTULO / TITLE: - Safety of the new macrolide
immunomodulators.
REVISTA
/ JOURNAL: - Semin Cutan Med Surg 2001 Dec;20(4):242-9.
AUTORES
/ AUTHORS: - Robinson N; Singri P; Gordon KB
INSTITUCIÓN
/ INSTITUTION: - Department of Dermatology, Northwestern
University, Chicago, IL 60611, USA.
RESUMEN
/ SUMMARY: - With the wide acceptance of cyclosporine
in the treatment of skin disease, there has been an effort to find new
immunomodulating agents with superior safety profiles for use in dermatology.
Among the most promising of the classes are the new macrolide immunomodulators,
including tacrolimus and pimecrolimus. Of these, only tocrolimus has had
widespread use for nondermatologic indications, primarily solid organ
transplantation. Both of these agents have been studied for inflammatory diseases
of the skin. In this article, we review the systemic and topical toxicities of
these macrolide immunomodulators. N.
Ref:: 68
----------------------------------------------------
[161]
TÍTULO / TITLE: - Bone marrow aplasia
after pipobroman: an immune-mediated mechanism?
REVISTA
/ JOURNAL: - Br J Haematol 2001 Dec;115(3):713-4.
AUTORES
/ AUTHORS: - Triffet A; Straetmans N; Ferrant A N. Ref:: 7
----------------------------------------------------
[162]
TÍTULO / TITLE: - Management of recurrent
hepatitis C after liver transplantation.
REVISTA
/ JOURNAL: - J Viral Hepat 2001 May;8(3):159-68.
AUTORES
/ AUTHORS: - Teixeira R; Papatheodoridis GV; Burroughs
AK
INSTITUCIÓN
/ INSTITUTION: - Liver Transplantation Unit, Royal Free
Hospital, Pond Street, London NW3 2QG, UK.
RESUMEN
/ SUMMARY: - Hepatitis C virus (HCV) reinfection is
almost universal in patients transplanted for HCV-related cirrhosis. The
medium-term survival after orthotopic liver transplantation (OLT) is similar to
other transplanted patients, but the long-term survival remains uncertain. The
prevention and an effective treatment of progressive liver disease are the
primary aims in HCV recurrence. Interferon and ribavirin, as monotherapy or in
combination, have been tried to treat or prevent HCV recurrence. Preliminary
studies suggest a better chance of initial HCV clearance and better results in
preventing HCV recurrence with combination therapy. IFN or ribavirin, as
monotherapy, may normalize liver enzymes, but only gives rise to a transient virological
response, without histological improvement. Combination IFN and ribavirin may
be able to prevent progression of HCV-related graft disease, but indications
and duration of treatment need further evaluation. No clear association between
type and dose of immunosuppressive and outcome of post-transplant HCV
recurrence has been found. Strategies to minimize the effects of
immunosuppressive drugs include dose reduction of all agents and the selective
discontinuation of individual agents. Initial immunosuppression with a single
drug may inhibit or delay the severe fibrosis, and further investigation with a
single immunosuppressive regimen to evaluate the outcome of recurrent hepatitis
C should be performed. The recent evidence that mycophenolate may have an
antiviral effect needs a clinical confirmation. Retransplantation survival is
better with early retransplantation, and for indications not directly related
to viral recurrence. N.
Ref:: 88
----------------------------------------------------
[163]
TÍTULO / TITLE: - Thrombotic
thrombocytopenic purpura following stem cell transplantation.
REVISTA
/ JOURNAL: - Leuk Lymphoma 2002 Oct;43(10):1921-6.
AUTORES
/ AUTHORS: - Allford SL; Bird JM; Marks DI
INSTITUCIÓN
/ INSTITUTION: - Adult BMT Unit, Bristol Royal Hospital for
Children, Upper Maudlin Street, Bristol BS2 8BJ, UK.
RESUMEN
/ SUMMARY: - Thrombotic thrombocytopenic purpura (TTP)
occurring after stem cell transplantation is poorly understood. The literature
is scant and heterogeneous; little is known about the condition’s pathogenesis
except that it appears to differ from that of classical or de novo TTP. There
are no widely agreed diagnostic criteria hence, it is difficult to compare the
major findings of the relatively small, single centre series that have been
reported. The true incidence is disputed and risk factors have only recently
been evaluated. Plasma exchange is commonly employed for the therapy of severe
post-transplant TTP but there are no data that support its use. This review
summarises the state of knowledge of post-transplant TTP in 2002, addressing
all the aforementioned issues and aims to provide the basis for further
systematic study of this problematic complication of transplant. N. Ref:: 35
----------------------------------------------------
[164]
TÍTULO / TITLE: - Immunomodulation in
stem-cell transplantation.
REVISTA
/ JOURNAL: - Curr Opin Pharmacol 2002 Aug;2(4):452-7.
AUTORES
/ AUTHORS: - Abo-Zena RA; Horwitz ME
INSTITUCIÓN
/ INSTITUTION: - Bone Marrow Transplant, National
Institutes of Health, Pharmacy Department Building 10, Room 1N-257, Bethesda,
Maryland 20892-1196, USA. rabozena@nih.gov
RESUMEN
/ SUMMARY: - Acute graft-versus-host disease is a
complication that affects 30-60% of patients undergoing allogeneic stem-cell
transplantation. The standard for prophylaxis for graft-versus-host disease has
historically been the combination of cyclosporine and methotrexate. Recently,
tacrolimus has been used more frequently and current studies are exploring the
potential of mycophenolate mofetil. There is little published experience with
the use of sirolimus in prophylaxis or treatment but studies are ongoing. There
have been significant advances recently in the treatment of steroid-refractory
acute graft-versus-host disease. Historically, antithymocyte globulin was used
when patients did not respond to the steroid treatment. New monoclonal
antibodies such as daclizumab, and tumor necrosis factor alpha inhibitors such
as infliximab are producing more promising results. Chronic graft-versus-host
disease continues to be a major complication of stem-cell transplantation,
affecting 35-50% of patients. Finding effective treatments for chronic
graft-versus-host disease other than steroids continues to be a challenge. N. Ref:: 45
----------------------------------------------------
[165]
TÍTULO / TITLE: - Neurotoxicology of the
brain barrier system: new implications.
REVISTA
/ JOURNAL: - J Toxicol Clin Toxicol 2001;39(7):711-9.
AUTORES
/ AUTHORS: - Zheng W
INSTITUCIÓN
/ INSTITUTION: - College of Physicians and Surgeons,
Columbia University, New York, New York 10032, USA. wz18@columbia.edu
RESUMEN
/ SUMMARY: - The concept of a barrier system in the brain
has existed for nearly a century. The barrier that separates the blood from the
cerebral interstitial fluid is defined as the blood-brain barrier, while the
one that discontinues the circulation between the blood and cerebrospinal fluid
is named the blood-cerebrospinal fluid barrier. Evidence in the past decades
suggests that brain barriers are subject to toxic insults from neurotoxic
chemicals circulating in blood. The aging process and some disease states
render barriers more vulnerable to insults arising inside and outside the
barriers. The implication of brain barriers in certain neurodegenerative
diseases is compelling, although the contribution of chemical-induced barrier
dysfunction in the etiology of any of these disorders remains poorly understood.
This review examines what is currently understood about brain barrier systems
in central nervous system disorders by focusing on chemical-induced
neurotoxicities including those associated with nitrobenzenes,
N-methyl-D-aspartate, cyclosporin A, pyridostigmine bromide, aluminum, lead,
manganese, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and 3-nitropropionic
acid. Contemporary research questions arising from this growing understanding
show enormous promises for brain researchers, toxicologists, and
clinicians. N. Ref:: 72
----------------------------------------------------
[166]
TÍTULO / TITLE: - Cytomegalovirus
infection and abdominal pain with mycophenolate mofetil: is there a link?
REVISTA
/ JOURNAL: - Drug Saf. Acceso gratuito al texto completo.
●●
Enlace a la Editora de la Revista http://www.csmwm.org/
●●
Cita: Drug Safety: <> 2001;24(6):405-12.
AUTORES
/ AUTHORS: - Gallagher H; Andrews PA
INSTITUCIÓN
/ INSTITUTION: - South West Thames Renal and Transplantation
Unit, St Helier Hospital, Carshalton, Surrey, England.
RESUMEN
/ SUMMARY: - Mycophenolate mofetil (MMF) is an
immunosuppressive agent that exerts relatively selective antiproliferative
effects on T and B lymphocytes. Efficacy has been demonstrated in large-scale
randomised studies, but the use of MMF is complicated by gastrointestinal upset
and is associated with an increased incidence of tissue-invasive
cytomegalovirus (CMV) disease. The gastrointestinal tract is a well recognised
site for invasive CMV disease, and it has therefore been hypothesised that the
abdominal pain commonly seen with MMF is related to CMV infection. This has
only been tested in a single small uncontrolled study, where abdominal pain was
associated with the presence of CMV on endoscopic biopsy. In contrast, the
toxicity profile in 85 patients with psoriasis who had received relatively high
dosages of mycophenolic acid, the active moiety of MMF, for up to 13 years
showed that the incidence of gastrointestinal upset fell dramatically over
time. We can find little evidence that CMV disease explains the
gastrointestinal adverse event profile associated with MMF, and instead support
the contention that high local concentrations of MMF have a direct toxic effect
on cells of the small intestine. We do not recommend any changes to current
policy on CMV prophylaxis in patients receiving MMF, although we recognise that
some severe gastrointestinal adverse effects may be CMV-associated. The use of
trough plasma concentration monitoring, divided doses and a gradually
increasing dosage schedule may be of value in limiting toxicity. N. Ref:: 48
----------------------------------------------------
[167]
TÍTULO / TITLE: - Overview of side
effects of immunosuppressive therapy.
REVISTA
/ JOURNAL: - Transplant Proc 2001 May;33(3):2089-91.
AUTORES
/ AUTHORS: - Paul LC
INSTITUCIÓN
/ INSTITUTION: - Department of Nephrology, Leiden
University Medical Center, Leiden, The Netherlands. N. Ref:: 21
----------------------------------------------------
[168]
TÍTULO / TITLE: - Cyclosporine-associated
encephalopathy: a case report and literature review.
REVISTA
/ JOURNAL: - Transplant Proc 2001
Nov-Dec;33(7-8):3700-1.
AUTORES
/ AUTHORS: - Chang SH; Lim CS; Low TS; Chong HT; Tan SY
INSTITUCIÓN
/ INSTITUTION: - Renal Unit, Department of Medicine,
University of Malaya Medical Center, Kuala Lumpur, Malaysia.
----------------------------------------------------
[169]
TÍTULO / TITLE: - Everolimus. Novartis.
REVISTA
/ JOURNAL: - Curr Opin Investig Drugs 2001
Sep;2(9):1220-34.
AUTORES
/ AUTHORS: - Dumont FJ
INSTITUCIÓN
/ INSTITUTION: - Merck Research Laboratories, Department of
Immunology & Rheumatology, 126 East Lincoln Avenue, PO Box 2000, Rahway, NJ
07065, USA. francis_dumont@merck.com
RESUMEN
/ SUMMARY: - Everolimus (RAD-001, SDZ RAD, Certican),
an analog of sirolimus, is an oral immunosuppressant that inhibits growth
factor-induced cell proliferation, under development by Novartis as a potential
treatment for transplant rejection. Phase III trials were initiated by the end
of 1998 [319337] and were ongoing in February 2001 [400448]. At the end of
2000, Novartis was hoping to file for approval of the compound in 2001
[392881], with a possible launch in mild-2002 [392881], [401979]. Completion of
phase III trials in heart transplant patients is expected this year and lung
and liver transplants by 2003. In 1999, American Home Products (AHP) initiated
an action for infringement of the patent EP-00401747, which covers the use of
sirolimus in transplantation in the UK, the Netherlands and Germany, seeking to
restrain the clinical trial program for everolimus. Novartis subsequently filed
a counterclaim for invalidity. In December 1999, the UK High Court of Justice
ruled that everolimus infringes the British counterpart of EP-00401747
[349637]. In contrast, in April 2000, the District Court of The Hague ruled
that everolimus does not infringe patent rights licensed to AHP [362823] and in
July 2000, The Court of Appeal in the UK came to the same conclusion [376559].
In February 2001, the Opposition Board at the European Patent Office upheld
Novartis’ European patent for everolimus, which the Board held to be
‘inventive’ [400448]. In July 2000, Vontobel estimated sales of SFr 80 million
in 2002, rising to SFr 800 million in 2004 [378871]. In February 2001, Merrill
Lynch predicted sales of SFr 125 million rising to SFr 661 million in 2005
[411704]. N. Ref:: 100
----------------------------------------------------
[170]
TÍTULO / TITLE: - Diagnosis and
management of refractoriness to platelet transfusion.
REVISTA
/ JOURNAL: - Blood Rev 2001 Dec;15(4):175-80.
●●
Enlace al texto completo (gratuito o de pago) 1054/blre.2001.0164
AUTORES
/ AUTHORS: - Schiffer CA
INSTITUCIÓN
/ INSTITUTION: - Karmanos Cancer Institute, Wayne State
University School of Medicine, Detroit, MI 48201, USA. schiffer@karmanos.org
RESUMEN
/ SUMMARY: - Improvements in the availability and
quality of platelet transfusions have markedly reduced the morbidity and
mortality associated with intensive myelosuppressive therapy. Alloimmunization
and refractoriness to platelet transfusion remains a significant clinical
problem, although the incidence of alloimmunization may be declining due to
more widespread use of leucocyte depleted products. Alloimmunization can be
distinguished from other causes of poor post transfusion increments by the
measurement of lymphocytotoxic or antiplatelet antibodies. In addition to
medical approaches to reduce the risk of bleeding in individual patients,
identification of histocompatible donors can usually be accomplished by HLA
matching of donor and recipient, platelet cross matching or a combination of
both techniques. There are a number of selection strategies which can be
utilized and optimal patient management requires close cooperation and
communication between clinicians and blood centers. N. Ref:: 48
----------------------------------------------------
[171]
TÍTULO / TITLE: - Calcineurin inhibitors
and post-transplant hyperlipidaemias.
REVISTA
/ JOURNAL: - Drug Saf. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.csmwm.org/
●●
Cita: Drug Safety: <> 2001;24(10):755-66.
AUTORES
/ AUTHORS: - Moore R; Hernandez D; Valantine H
INSTITUCIÓN
/ INSTITUTION: - University of Cardiff, Wales, United
Kingdom. Richard.Moore@UHW-TR.wales.nhs.uk
RESUMEN
/ SUMMARY: - Cardiovascular disease is now the leading
cause of death in transplant recipients. This is due, in part, to the vulnerability
of these patients to a complicated set of conditions including hypertension,
diabetes mellitus, and post-transplant hyperlipidaemia (PTHL). PTHL is
characterised by persistent elevations in total serum cholesterol, low density
lipoprotein cholesterol and triglyceride levels. The causes of PTHL are complex
and not fully understood, however several classes of immunosuppressants
including the corticosteroids, rapamycins and calcineurin inhibitors, appear to
play a role. PTHL has been observed in most studies in which patients received
calcineurin inhibitor-based regimens, and has been observed with both
tacrolimus and cyclosporin. Comparing these calcineurin inhibitors with regard
to the relative incidence or severity of PTHL occurring during treatment is
difficult because of the use of higher doses of corticosteroids in
cyclosporin-based regimens, as compared with tacrolimus-based regimens.
However, current expert opinion suggests that the discrepancies in the relative
incidence and severity of PTHL are largely accounted for by this difference in
corticosteroid dose. At this point in time, evidence for potential differences
is scant and inconclusive. Further study is needed, not only to investigate
differences in lipid profile, but also of the relative effects of these
immunosuppressants on long term graft function as well as on cardiovascular
morbidity and mortality. PTHL can be successfully managed with a combination of
dietary management, reduction and, if appropriate, withdrawal of
corticosteroids, and the administration of lipid-lowering drugs. With this
combination of therapeutic options, the threats to long term health posed by
PTHL may be effectively addressed. N.
Ref:: 98
----------------------------------------------------
[172]
TÍTULO / TITLE: - Impact of
immunosuppressive regimes on posttransplant diabetes mellitus.
REVISTA
/ JOURNAL: - Transplant Proc 2001 Aug;33(5A
Suppl):23S-26S.
AUTORES
/ AUTHORS: - Weir M
INSTITUCIÓN
/ INSTITUTION: - Division of Nephology, University of
Maryland Hospital, Baltimore, Maryland 21201, USA. N. Ref:: 44
----------------------------------------------------
[173]
TÍTULO / TITLE: - Stent restenosis and
the use of drug-eluting stents in patients with diabetes mellitus.
REVISTA
/ JOURNAL: - Curr Diab Rep 2004 Feb;4(1):13-9.
AUTORES
/ AUTHORS: - Sarembock IJ
INSTITUCIÓN
/ INSTITUTION: - Cardiovascular Division and Cardiovascular
Research Center, University of Virginia Health System, Box 800158,
Charlottesville, VA 22908-0158, USA. ijs4s@virginia.edu
RESUMEN
/ SUMMARY: - Stents have become the technique of choice
for percutaneous revascularization, but in-stent restenosis has remained a
clinical challenge. This brief article summarizes the incidence, patterns, and
proposed mechanisms of restenosis and outlines its contemporary management with
specific focus on the diabetic patient. It includes a synopsis of the strategy
of drug-eluting stents, which is the most recent and major advance in
percutaneous coronary intervention. N.
Ref:: 65
----------------------------------------------------
[174]
TÍTULO / TITLE: - Cyclosporine in severe
psoriasis. Results of a meta-analysis in 579 patients.
REVISTA
/ JOURNAL: - Am J Clin Dermatol 2001;2(1):41-7.
AUTORES
/ AUTHORS: - Faerber L; Braeutigam M; Weidinger G;
Mrowietz U; Christophers E; Schulze HJ; Mahrle G; Meffert H; Drechsler S
INSTITUCIÓN
/ INSTITUTION: - Department of Pharmacology, University of
Regensburg, Regensburg, Germany.
RESUMEN
/ SUMMARY: - OBJECTIVE: A meta-analysis of 3 major
German studies conducted between 1989 and 1994 with cyclosporine in severe
psoriasis was performed to allow an integrated evaluation of the efficacy and
tolerability of cyclosporine in this indication. DESIGN AND SETTING: All 3
studies were prospective, randomized, parallel group studies. The studies were
conducted in 61 dermatologic centers in Germany. PATIENTS AND INTERVENTIONS:
The studies involved 597 patients with severe plaque type psoriasis. Treatment
consisted of cyclosporine (at a dosage of 1.25, 2.5 or 5 mg/kg/day), etretinate
(at a mean daily dose of 0.53 mg/kg/day) or placebo in a total of 756 treatment
cycles with a maximum duration of 12 weeks. MAIN OUTCOME MEASURES: The main
outcome measures were the psoriasis area and severity index (PASI) and serum
creatinine level. RESULTS: The meta-analysis revealed that cyclosporine given
in a dosage of 2.5 and 5 mg/kg/day was significantly superior to etretinate. In
addition cyclosporine 1.25 mg/kg/day proved to be significantly more effective
than placebo. An increase in serum creatinine level that required intervention
occurred in 3.4% of cyclosporine treatment cycles. CONCLUSION: Cyclosporine is
highly effective and well tolerated in the short term treatment of severe
psoriasis.
----------------------------------------------------
[175]
TÍTULO / TITLE: - Pregnancy associated
aplastic anemia—a series of 10 cases with review of literature.
REVISTA
/ JOURNAL: - Hematology 2002 Aug;7(4):233-8.
●●
Enlace al texto completo (gratuito o de pago) 1080/1024533021000024067
AUTORES
/ AUTHORS: - Choudhry VP; Gupta S; Gupta M; Kashyap R;
Saxena R
INSTITUCIÓN
/ INSTITUTION: - Department of Hematology, All India
Institute of Medical Sciences, New Delhi 110029, India. vedpchoudhry@yahoo.co.in
RESUMEN
/ SUMMARY: - Introduction: Pregnancy induced aplastic
anemia is a rare entity and the association is not well explained. There are
approximately 80 cases in the literature and we are presenting the largest
series, so far, of 10 cases.Results: Total of 10 cases had 11 pregnancies. Mean
age at presentation was 25.45 years and mean gestation when symptoms first
developed was 17.09 weeks. Pallor and bleeding manifestations were the most
common presenting complaints. Mean Hb, TLC, ANC and platelets were 4.97 g/dl,
2.74 x 10(9)/l, 1.11 x 10(9)/l and 41 x 10(9)/l, respectively. Bone biopsy
cellularity ranged from <5 to 25%. Nine out of 11 (81%) pregnancies were
successful of which 7 was full term and 2 were premature. Two babies were small
for dates. One spontaneous abortion and one intra uterine death (IUD) were
observed. Two out of 11 mothers died due to disease after delivery. Two of the
8 surviving mothers, had spontaneous partial response (22%); 4 mothers were
asymptomatic after therapy with immunosuppressives given for 6 months and 3
were lost to follow up without response. Specific therapy (cyclosporin) was
tried in two mothers antenatally with partial response in one. One child whose
mother was given cyclosporin antenatally had jejunal atresia at
birth.Conclusion: Pregnancy associated aplastic anemia is a rare association.
Spontaneous remission can occur in 25-30% of patients. In the first trimester
patients, pregnancy can be terminated while in advanced pregnancy patients can
be followed up with stringent supportive care. Cyclosporin may be a safe drug
antenatally in such patients. Patients with established aplastic anemia should
avoid pregnancy. N.
Ref:: 23
----------------------------------------------------
[176]
TÍTULO / TITLE: - Lichen planus
esophagitis: report of three patients treated with oral tacrolimus or
intraesophageal corticosteroid injections or both.
REVISTA
/ JOURNAL: - Dis Esophagus 2003;16(1):47-53.
AUTORES
/ AUTHORS: - Keate RF; Williams JW; Connolly SM
INSTITUCIÓN
/ INSTITUTION: - Division of Gastroenterology and
Hepatology, Mayo Clinic, Scottsdale, AZ 85259, USA. keate.ray@mayo.edu
RESUMEN
/ SUMMARY: - Clinically significant involvement of the
esophagus is uncommon in patients who have lichen planus, a common disorder of
squamous epithelium. In three patients who had oral, cutaneous, and esophageal
lichen planus, endoscopic intralesional esophageal injection of corticosteroids
(in all three patients) and oral tacrolimus (FH506) (in two patients) resulted
in improvement in dysphagia, a less frequent need for dilation, and improvement
in esophageal inflammation. N.
Ref:: 36
----------------------------------------------------
[177]
TÍTULO / TITLE: - Prevention and
treatment of severe hemodynamic compromise in pediatric heart transplant
patients.
REVISTA
/ JOURNAL: - Paediatr Drugs 2002;4(11):705-15.
AUTORES
/ AUTHORS: - Costello JM; Pahl E
INSTITUCIÓN
/ INSTITUTION: - Division of Pulmonary and Critical Care
Medicine, Department of Pediatrics, The Children’s Memorial Hospital, Feinberg
School of Medicine at Northwestern University, Chicago, Illinois 60614, USA.
RESUMEN
/ SUMMARY: - Allograft rejection is a leading cause of
severe hemodynamic compromise in pediatric heart transplant patients. A
triple-drug immunosuppression regimen, which includes a calcineurin inhibitor,
antiproliferative agent, and corticosteroid, suppresses the immune system at
multiple different levels for optimal graft protection while minimizing the
adverse effects of any one particular agent. Some pediatric centers also use
induction therapy with anti-T cell antibodies immediately following
transplantation as additional rejection prophylaxis. These antibodies augment
immunosuppression by either depleting the T cell pool or blocking interleukin-2
receptors on activated T cells. Despite the aggressive preventive measures
outlined above, some pediatric heart transplant patients will develop severe
hemodynamic compromise, most commonly due to fulminant rejection. Such patients
require attention to, and optimization of, the four determinants of cardiac
output (heart rate, preload, contractility and afterload) to stabilize the
circulation until the rejection can be reversed. Careful administration of
volume, diuretics, inotropes, and afterload-reducing agents will meet this
goal. Patients with allograft rejection require augmentation of immune
suppression to facilitate myocardial recovery. Corticosteroids form the
cornerstone of treatment for both cellular and vascular rejection. In patients
with refractory cellular rejection, conversion to mycophenolate mofetil or
tacrolimus may be appropriate if these agents are not already being used for
maintenance immunosuppression. Critically ill patients may additionally benefit
from muromonab-CD3 (OKT3) to augment lympholysis. Treatment employed
specifically for humoral rejection is prescribed with the intention of suppressing
new antibody formation, removing circulating antibody, and improving coronary
blood flow. In addition to corticosteroids, cyclophosphamide and antithymocyte
globulin or muromonab-CD3, along with plasmapheresis, may improve survival.
Systemic heparinization should be considered to minimize coronary thrombosis in
patients with humoral rejection. In the future, novel immunosuppressive agents
may further assist in the prevention as well as treatment of severe hemodynamic
compromise due to rejection in pediatric heart transplant recipients. N. Ref:: 99
----------------------------------------------------
[178]
TÍTULO / TITLE: - Novel therapeutics for
the treatment of graft-versus-host disease.
REVISTA
/ JOURNAL: - Expert Opin Investig Drugs 2002
Sep;11(9):1271-80.
AUTORES
/ AUTHORS: - Jacobsohn DA
INSTITUCIÓN
/ INSTITUTION: - Department of Pediatrics, Northwestern
University, Feinberg School of Medicine, Chicago, IL, USA.
RESUMEN
/ SUMMARY: - Acute graft-versus-host disease (GVHD) and
chronic GVHD remain the major barriers to successful haematopoietic cell
transplantation. The induction of GVHD may be divided into three phases:
recipient conditioning, donor T cell activation and effector 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 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 TNF-alpha. Cyclosporin, FK506 and sirolimus are some of
the main agents that disrupt Phase II (donor T cell activation). Mycophenolate
mofetil likely acts on this phase as well. Other novel drugs that affect Phase
II are tolerance-induction agents such as cytotoxic T lymphocyte antigen
(CTLA)-4 Ig and anti-CD40 ligand, and preliminary results using CTLA-4 Ig in
GVHD prevention are encouraging. Two exciting agents that appear to affect only
activated lymphocytes are ABX-CBL and visilizumab. Examples of agents that
disrupt Phase III are the IL-2 receptor antagonist daclizumab and the
anti-TNF-alpha monoclonal antibody infliximab. These anticytokine antibodies have
shown promising results in early studies. The most effective approach to GVHD
prevention will likely 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 will likely yield better results than monotherapy.
The numerous new treatment modalities presented should improve the outlook for
acute and chronic GVHD. N.
Ref:: 81
----------------------------------------------------
[179]
TÍTULO / TITLE: - Obesity in transplant
patients: case report showing interference of orlistat with absorption of
cyclosporine and review of literature.
REVISTA
/ JOURNAL: - Endocr Pract 2002 Mar-Apr;8(2):124-6.
AUTORES
/ AUTHORS: - Barbaro D; Orsini P; Pallini S; Piazza F;
Pasquini C
INSTITUCIÓN
/ INSTITUTION: - Sezione Endocrinologia, Diabetologia e
Malattie Metaboliche, Spedali Riuniti, Azienda U.S.L. n6 di Livorno, Livorno,
Italy.
RESUMEN
/ SUMMARY: - OBJECTIVE: To report a case of an obese
patient who had undergone renal transplantation and who had subtherapeutic
levels of serum cyclosporine after treatment with orlistat. METHODS: The
clinical and laboratory findings are presented, and the few cases reported in
the literature are reviewed. RESULTS: A 29-year-old woman had subtherapeutic
plasma levels of cyclosporine after orlistat treatment (360 mg/day) was
initiated. The subtherapeutic levels persisted even though orlistat was
administered the recommended 2 hours before ingestion of cyclosporine and even
though the dosage of orlistat was decreased to only 240 mg/day. Because an
increase of body weight is common after organ transplantation, treatment with
orlistat has been used. In such patients, however, six cases of reduced
therapeutic plasma levels of cyclosporine have been reported. Although a
drug-drug interaction has been suggested, this case suggests that the decreased
plasma cyclosporine levels are due to reduced absorption of fats rather than a
drug-drug interaction. Because this patient was unable to adhere to a low-fat
diet, she experienced severe diarrhea, a factor that may have dramatically
diminished the absorption of cyclosporine. CONCLUSION: Adherence to a low-fat
diet should be strongly recommended if orlistat is prescribed to patients
taking cyclosporine. Moreover, strict surveillance of the plasma concentration
of cyclosporine is important. N.
Ref:: 17
----------------------------------------------------
[180]
TÍTULO / TITLE: - Small molecule
immunosuppressive agents in experimental and clinical transplantation.
REVISTA
/ JOURNAL: - Curr Drug Targets Cardiovasc Haematol
Disord 2002 Dec;2(2):57-71.
AUTORES
/ AUTHORS: - Ma A; Chen H
INSTITUCIÓN
/ INSTITUTION: - Laboratory of Experimental Surgery,
Research Center of CHUM, Notre-Dame Hospital, University of Montreal, 1560
Sherbrooke Street East, Montreal, Quebec, Canada.
RESUMEN
/ SUMMARY: - Immunosuppression is currently the major
approach used for the prevention and management of transplant rejection. In
this overview, preclinical and clinical studies of the small molecule
immunosuppressive agents are reviewed from the discovery of cyclosporine. More
recently it was demonstrated that certain agents, namely tacrolimus (FK506), sirolimus
(rapamycin), and mycophenolate mofetil (CellCept, MMF), act selectively on
adaptive host responses at different stages of T- and B-cell cycles and spare
nonspecific host resistance. Because each agent has its specific and
significant toxic effects, it has been difficult to optimize the use of
individual agents in monotherapy. Therefore, drug combination therapy has been
of great interest in addition to the introduction of new small molecule agents,
such as malononitrilamides [MNAs (leflunomide, FK778, FK779)],
15-deoxyspergualin (DSG) and its analogues, FTY720 and inhibitors of signal
transduction, which offer promising modes of immunosuppression. N. Ref:: 129
----------------------------------------------------
[181]
TÍTULO / TITLE: - A case of persistent
anemia in a renal transplant recipient: association with parvovirus B19
infection.
REVISTA
/ JOURNAL: - Scand J Infect Dis 2002;34(1):71-5.
AUTORES
/ AUTHORS: - Choi SH; Chang SP; Won JC; Lee JS; Chi HS;
Yang WS; Park SK
INSTITUCIÓN
/ INSTITUTION: - Department of Internal Medicine, Ulsan
University College of Medicine, Seoul, South Korea.
RESUMEN
/ SUMMARY: - We report an unexplained anemia that
persisted for 4 months in a renal transplant patient who was receiving
immunosuppression therapy that included prednisolone, tacrolimus and
azathioprine. A bone marrow biopsy demonstrated pure erythroid hypoplasia and
occasional giant pronormoblasts with intranuclear inclusions, characteristic of
a parvovirus B19 infection. Both the serum and bone marrow cells were positive
by parvovirus B19 DNA PCR. The anemia resolved 6 weeks after the administration
of intravenous immunoglobulin (IVIG). Four months later, anemia redeveloped and
IVIG was infused again. Hemoglobin levels were, however, still subnormal after
1 month of treatment and tacrolimus was then switched to cyclosporin A,
resulting in a clear improvement. A parvovirus B19 infection should be included
in the differential diagnosis of renal transplant recipients who present with
anemia associated with a low reticulocyte count. Tacrolimus may possibly impair
the clearance of a parvovirus B19 infection.
N. Ref:: 21
----------------------------------------------------
[182]
TÍTULO / TITLE: - New developments in the
prophylaxis and treatment of graft versus host disease.
REVISTA
/ JOURNAL: - Expert Opin Pharmacother 2001
Jul;2(7):1109-17.
AUTORES
/ AUTHORS: - Simpson D
INSTITUCIÓN
/ INSTITUTION: - North Shore Hospital, Auckland, New
Zealand. david.simpson@whl.co.nz
RESUMEN
/ SUMMARY: - Graft versus host disease (GVHD) remains
the major obstacle to successful allogeneic bone marrow transplantation.
Cyclosporin with methotrexate is the most common prophylactic regimen.
Tacrolimus is associated with less GVHD and is gaining ground especially in
unrelated donor transplants where current regimens are unsatisfactory.
Mycophenolate mofetil (MMF) and rapamycin have not yet shown benefit in acute
GVHD prophylaxis. In vivo T-cell depletion with Campath 1H or thymoglobulin
used during transplant conditioning are increasingly used in place of ex vivo
T-cell depletion, where results remain disappointing. Steroids remain first
choice for therapy of GVHD but anti-CD25 antibodies, daclizumab or basiliximab
are gaining popularity as second-line therapy ahead of ATG. Chronic GVHD is
increasing with greater use of peripheral blood stem cell grafts and older
patients. The combination of tacrolimus and MMF is promising for patients with
extensive disease. Tolerance induction using CTLA-4-Ig, anti-CD40L, tresperimus
and/or rapamycin may revolutionise GVHD therapy. However, due to the
desirability of tumour intolerance, tolerance is likely to be developed in
organ transplantation before bone marrow transplantation for traditional
indications. Bone marrow transplants performed to induce organ tolerance may
see increasing use of these agents. TNF blockade using infliximab or etanercept
(Enbrel) is promising but the role of these agents is not yet defined. N. Ref:: 68
----------------------------------------------------
[183]
TÍTULO / TITLE: - Strategies for
minimizing hyperlipidemia after cardiac transplantation.
REVISTA
/ JOURNAL: - Am J Cardiovasc Drugs 2002;2(6):377-87.
AUTORES
/ AUTHORS: - Kirklin JK; Benza RL; Rayburn BK; McGiffin
DC
INSTITUCIÓN
/ INSTITUTION: - Department of Surgery, Division of
Cardiothoracic Surgery, University of Alabama at Birmingham, Birmingham,
Alabama 35294, USA. jkirklin@uab.edu
RESUMEN
/ SUMMARY: - Allograft coronary artery disease
represents a major limitation to long-term survival after cardiac
transplantation. Hyperlipidemias have been linked to the development of native
coronary atherosclerosis, and hyperlipidemic states have correlated with the
severity of allograft coronary artery disease. Heart transplant recipients
typically manifest increases in plasma levels of total cholesterol, low-density
lipoprotein-cholesterol (LDL-C), and triglycerides within the first 3-12 months
following transplantation. Factors known to promote post-transplant
hyperlipidemia include the use of corticosteroids, cyclosporine (interference
with clearance and increased oxidizability of LDL), sirolimus
(hypertriglyceridemia), and patient-specific causes of hyperlipidemia which
contributed to their underlying heart disease. Hydroxymethylglutaryl coenzyme-A
(HMG-CoA) reductase inhibitors are the foundation of antilipid therapy
following cardiac transplantation. Pravastatin is effective in lowering plasma
cholesterol levels and is associated with a decreased incidence and progression
of allograft coronary artery disease. All HMG-CoA reductase inhibitors except
pravastatin are metabolized by the hepatic cytochrome P450 system which
metabolizes cyclosporine, increasing the risk of myostitis when they are used
in large dosages with cyclosporine. Simvastatin, atorvastatin and fluvastatin
have been studied in heart transplant recipients. Gemfibrozil has proved
effective in transplant recipients when there is isolated marked elevation of plasma
triglyceride levels. When hyperlipidemia persists despite therapy, some benefit
may result with conversion from cyclosporine to tacrolimus. Although a
definitive link between hyperlipidemia and allograft coronary disease has yet
to be proven, available evidence points to abnormal lipid metabolism as part of
the complex etiologic machinery driving the process of ‘chronic rejection’.
Consensus exists within the transplant community that a HMG-CoA reductase
inhibitor such as pravastatin, should be part of the routine post-transplant
drug regimen, and persistent hyperlipidemia should be aggressively
treated. N. Ref:: 83
----------------------------------------------------
[184]
TÍTULO / TITLE: - Tresperimus: a new
agent for transplant tolerance induction.
REVISTA
/ JOURNAL: - Expert Opin Investig Drugs 2001
Jul;10(7):1381-6.
AUTORES
/ AUTHORS: - Simpson D
INSTITUCIÓN
/ INSTITUTION: - North Shore Hospital, Private Bag 93-503,
Takapuna, Auckland, New Zealand. david.simpson@whl.co.nz
RESUMEN
/ SUMMARY: - Tresperimus is a novel agent that induces
allogeneic transplant tolerance. It is structurally related to deoxyspergualin
(DSG) but has been modified to resist rapid hydrolysis in aqueous solution,
which simplifies administration. Despite this modification, tresperimus’s
actions in experimental models seem almost identical to DSG. Initially, DSG was
developed as an antitumour agent. Its antitumour efficacy appears limited but
DSG and tresperimus have favourable effects on transplant rejection. A short
course of tresperimus has been shown to have similar or greater quantitative
effects to cyclosporin in bone marrow, cardiac and skin transplant models.
However, qualitatively the effects are different. Prevention of rejection is
due to induction of donor-specific tolerance without affecting immunity to
third party antigens. In addition, CD4+ T-cells from tresperimus-treated
animals can transfer donor specific tolerance to naive animals, an effect not
seen with cyclosporin or other traditional immunosuppressive drugs. The
mechanism by which tolerance is induced is not clear. Tresperimus (like DSG)
binds to Hsc70, which among other effects inhibits nuclear localisation of
NF-kappa B. NF-kappa B nuclear localisation is induced by CD40 ligation in
antigen-presenting cells, an important early step in T-cell co-stimulation.
NF-kappa B is also required for CD28 ligation signalling, important in late
co-stimulation. It also is involved in B-cell activation, via CD40 ligation and
kappa light chain production. Hsc70 is also required for efficient cytosolic
peptide chaperoning to MHC class I molecules. Presumably, it is disruption of
T-cell/dendritic cell interaction that leads to induction of T-cell anergy.
Tresperimus is well-tolerated. The main dose limiting side effects are
orthostatic hypotension and peri-oral numbness. These effects are dependant on
blood drug levels and, due to its short half-life, correspond to the rate of
infusion. Phase II/III clinical studies are accruing patients and results have
not yet been reported. Tresperimus shows promise in the move from
immunosuppression to tolerance induction as the way to prevent transplant
rejection and graft versus host disease (G v HD). However, its role in
tolerance induction and effect in combination with other tolerance inducing
agents e.g., CTLA-4-Ig and anti-CD40L antibodies remains unclear. N. Ref:: 36
----------------------------------------------------
[185]
TÍTULO / TITLE: - The Epstein-Barr virus
and post-transplant lymphoproliferative disease: interplay of
immunosuppression, EBV, and the immune system in disease pathogenesis.
REVISTA
/ JOURNAL: - Transpl Infect Dis 2001 Jun;3(2):60-9.
AUTORES
/ AUTHORS: - Tanner JE; Alfieri C
INSTITUCIÓN
/ INSTITUTION: - Department of Pediatrics, Children’s
Hospital of Eastern Ontario, University of Ottawa Medical School, Ottawa,
Ontario, Canada.
RESUMEN
/ SUMMARY: - Transplant patients are at particular risk
for developing post-transplant lymphoproliferative disease (PTLD) following
administration of immunosuppressive therapy. In many cases the PTLD lesions
express Epstein-Barr virus (EBV) latent and lytic genes as well as elevated
levels of host cytokines. An outline of the potential contributions of EBV,
host cytokines and T cells, and the immunosuppressive cyclosporine A,
tacrolimus, and anti-CD3 antibody in the mechanism and pathogenesis of this
disease is presented and discussed. N.
Ref:: 145
----------------------------------------------------
[186]
TÍTULO / TITLE: - Therapy for acute
rejection in pediatric organ transplant recipients.
REVISTA
/ JOURNAL: - Paediatr Drugs 2003;5(2):81-93.
AUTORES
/ AUTHORS: - Debray D; Furlan V; Baudouin V; Houyel L;
Lacaille F; Chardot C
INSTITUCIÓN
/ INSTITUTION: - Paediatric Hepatology Unit, University
Hospital of Bicetre, Le Kremlin Bicetre, France.
RESUMEN
/ SUMMARY: - Despite the availability of potent
immunosuppressive drugs, rejection after organ transplantation in children
remains a serious concern, and may lead to significant morbidity, graft loss,
and death of the patient. Acute graft rejection in pediatric recipients is
first treated with methylprednisolone pulses, followed by progressive taper of
corticosteroid doses. After control of the rejection episode, baseline immunosuppression
has to be adjusted and closely monitored since rejection (especially late
episodes, occurring more than 6 months after transplantation) may be due to a
lack of compliance or sub-therapeutic drug concentrations. The management of
corticosteroid resistant rejection is not standardized, and depends on the
transplanted organ and previous immunosuppressive regimen. In patients
experiencing corticosteroid resistant acute rejection while on a
cyclosporine-based immunosuppressive regimen, cyclosporine is generally changed
to tacrolimus. In case of tacrolimus-based immunosuppression, tacrolimus blood
levels may be increased, and/or mycophenolate mofetil (which nowadays tends to
replace azathioprine) or sirolimus may be added, although pharmacodynamic data
and clinical studies with these agents are still scarce in pediatric
recipients. The use of antithymocyte globulins or monoclonal anti-CD3
antibodies, muromonab CD3 (OKT3) is hampered by numerous adverse effects,
including a significant risk of over-immunosuppression. These therapies are
nowadays indicated in very selected cases. Other treatments such as
plasmapheresis and high dose immunoglobulins may be useful in difficult cases.
In patients with refractory rejection despite therapeutic escalation, the risks
of over-immunosuppression, including opportunistic infections and malignancies
(especially the Epstein-Barr virus related post-transplant lymphoproliferative
disease) have to be balanced with the consequences of graft loss due to
rejection. Detransplantation or retransplantation may, in some instances, be
preferable to severe infectious or tumoral complications. N. Ref:: 157
----------------------------------------------------
[187]
TÍTULO / TITLE: - Steroid-refractory
graft-vs.-host disease: past, present and future.
REVISTA
/ JOURNAL: - Pediatr Transplant 2003;7 Suppl 3:19-31.
AUTORES
/ AUTHORS: - Carpenter PA; Sanders JE
INSTITUCIÓN
/ INSTITUTION: - Fred Hutchinson Cancer Research Center and
University of Washington, Department of Pediatrics, Seattle, WA 98109, USA.
RESUMEN
/ SUMMARY: - Despite current standard preventive
strategies that include optimizing donor selection and the combination of
methorexate and a calcineurine inhibitor, acute and chronic GVHD remains a
major barrier to successful hematopoietic cell transplantation for a sizeable
proportion of patients. When acute and chronic GVHD become manifest a standard
primary therapy approach has been the addition of glucocorticoid therapy to a
background of calcineurine inhibition. When this approach fails patients with
GVHD require secondary therapy. Ideally, second-line agents should promote
transplantation tolerance so that the morbidity associated with prolonged use
of glucocorticoids and other immunosuppressive agents can be minimized.
Promising new agents or strategies which warrant further controlled clinical
trials include: mycophenolate mofetil, sirolimus, humanized or chimeric
monoclonal antibodies such as visilizumab, daclizumab and infliximab, and
extracorporeal photopheresis. Co-operative studies are necessary to hasten the
process of evaluating novel treatment strategies for acute and chronic
GVHD. N. Ref:: 81
----------------------------------------------------
[188]
TÍTULO / TITLE: - Tacrolimus-associated
hemolytic uremic syndrome: a case analysis.
REVISTA
/ JOURNAL: - J Nephrol. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.jnephrol.com/
●●
Cita: Journal of Nephrology: <> 2003 Jul-Aug;16(4):580-5.
AUTORES
/ AUTHORS: - Lin CC; King KL; Chao YW; Yang AH; Chang
CF; Yang WC
INSTITUCIÓN
/ INSTITUTION: - Division of Nephrology, Department of
Medicine, Taipei Veterans General Hospital and School of Medicine, National
Yang-Ming University, Taipei, Taiwan, Republic of China. lincc2@vghtpe.gov.tw
RESUMEN
/ SUMMARY: - BACKGROUND: Tacrolimus is an effective
organ transplantation immunosuppressant. Hemolytic uremic syndrome (HUS) is a
rare but severe complication of tacrolimus. METHODS: We report a case of
tacrolimus-associated HUS and review the 15 previously reported cases. RESULTS:
The results of the 16 cases indicated that tacrolimus-associated HUS is more
frequent in females (56.3%), with the mean age at onset of 41.3 years.
Forty-four percent of cases received renal transplantations. The average time
from the first tacrolimus dose to HUS onset was 7.1 months. Prevalence was
between 0.14.7%. The tacrolimus trough level did not predict the prognosis.
Seven patients (43.7%) had improved graft function after treatment, including
anticoagulation and antiplatelet therapy, reduction or discontinuation of
tacrolimus, switch to cyclosporine (CyA), plasma exchange (PE) and dialysis.
Five patients (31.3%) died and four patients (25%) lost their graft in spite of
the above treatment. Mortality risk factors for transplant recipients with
tacrolimus-associated HUS included: (1) non-renal transplant recipients (100%
vs. 36.4%, p = 0.034); (2) lower peak serum Cr (2.58 +/- 1.23 vs. 6.16 +/-
1.96, p < 0.002); (3) liver dysfunction (60% vs. 0, p < 0.02); (4) higher
serum lactate dehydrogenase (LDH) level (3119 +/- 1019 vs. 982 +/- 522, p <
0.001). A lower platelet count carried borderline mortality risk (29500 +/-
14480 vs. 59625 +/- 25584, p = 0.057). CONCLUSIONS: HUS should be included in
the differential diagnosis of renal function deterioration in patients on
tacrolimus post-organ transplantation. Frequent renal function monitoring and
appropriate treatment should be performed aggressively to decrease morbidity
and mortality, especially in patients with risk factors. N. Ref:: 22
----------------------------------------------------
[189]
TÍTULO / TITLE: - Treatment of the
extraintestinal manifestations of inflammatory bowel disease.
REVISTA
/ JOURNAL: - Curr Gastroenterol Rep 2002
Dec;4(6):513-6.
AUTORES
/ AUTHORS: - Bernstein CN
INSTITUCIÓN
/ INSTITUTION: - Inflammatory Bowel Disease Clinical and
Research Centre, University of Manitoba, John Buhler Research Centre, 804F-715
McDermot Avenue, Winnipeg, Manitoba, Canada R3E 3P4. cbernst@cc.umanitoba.ca
RESUMEN
/ SUMMARY: - There is a paucity of randomized,
controlled therapy studies of the extraintestinal manifestations of
inflammatory bowel disease (IBD). Most current therapeutic approaches are
empiric or based on approaches to therapy in other settings. In the past year
anecdotal evidence has emerged for the use of therapies that neutralize tumor
necrosis factor-a in both ankylosing spondylitis and the dermatologic
extraintestinal manifestations. Topical tacrolimus has also emerged as a
potentially useful therapy for dermatologic manifestations. Finally, patients
with IBD occasionally become transplant recipients. One study reported
worsening IBD after orthotopic liver transplantation for primary sclerosing
cholangitis, and another reported the benefit of renal transplantation in
amyloidosis-induced renal failure. N.
Ref:: 28
----------------------------------------------------
[190]
TÍTULO / TITLE: - Pregnancy in renal
transplant recipients.
REVISTA
/ JOURNAL: - Adv Ren Replace Ther 2003 Jan;10(1):40-7.
●●
Enlace al texto completo (gratuito o de pago) 1053/jarr.2003.50002
AUTORES
/ AUTHORS: - Hou S
INSTITUCIÓN
/ INSTITUTION: - Section of Nephrology, Department of
Medicine, Loyola University Medical Center, Chicago, IL, USA. shou@lumc.edu
RESUMEN
/ SUMMARY: - Most women of childbearing age who receive
a renal transplant have a return of normal menses and have the ability to
become pregnant. Most studies indicate that pregnancy does not adversely affect
the transplant kidney’s survival as long as renal function is good and serum
creatinine is stable before pregnancy. The experience with immunosuppressive
drugs has been surprisingly reassuring with no increase in congenital anomalies
with cyclosporine, prednisone, and azathioprine. There is little experience
with newer drugs. Pregnant transplant recipients need to be monitored for
opportunistic infections, which may adversely affect the fetus, including
herpes, toxoplasmosis, and CMV. Hypertension, urinary tract infections, and
anemia are other common problems in pregnant transplant recipients. Despite a
high frequency of premature births, over 80% of pregnancies result in surviving
infants. N. Ref:: 38
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[191]
TÍTULO / TITLE: - Immunosuppressive drugs
in paediatric liver transplantation.
REVISTA
/ JOURNAL: - Paediatr Drugs 2001;3(1):43-60.
AUTORES
/ AUTHORS: - van Mourik ID; Kelly DA
INSTITUCIÓN
/ INSTITUTION: - Liver Unit, The Birmingham Children’s
Hospital NHS Trust, England. Tracey.Ellis@bhamchildrens.wmids.nhs.uk
RESUMEN
/ SUMMARY: - Orthotopic liver transplantation is
established treatment for children with acute and chronic liver failure.
Despite advances in pre- and postoperative management, innovative surgical
techniques and new immunosuppressive drugs, acute and chronic rejection remains
a problem. In addition, well established adverse effects of commonly used
immunosuppressive drugs are no longer accept able. More potent, but less toxic,
immunosuppressive agents have been developed and some novel compounds are now
entering routine practice. Cyclosporin was the cornerstone of immunosuppressive
therapy until the introduction of its novel pharmaceutical form (Neoral) with
improved bioavailability, lower inter- and intraindividual pharmacokinetic
variability and improved graft survival. Recently, tacrolimus, a macrolide drug
with a similar mode of action, but much higher potency, was introduced and, at
present, is the only agent which can successfully replace cyclosporin as a
first-line immunosuppressive drug. Mycophenolate mofetil has recently been approved
for use in adult and paediatric renal transplant recipients. It has a similar
mode of action to cyclosporin and tacrolimus, but acts at a later stage of the
T cell activation pathway. Administration with standard immunosuppressive drugs
reduces the incidence of acute rejection and enables cyclosporin and tacrolimus
dose reduction, thus reducing the risk of associated toxic effects. Phase I and
II trials with sirolimus (rapamycin), a macrolide antibiotic, have shown
comparable immunosuppressive action, when administered in conjunction with
standard immunosuppressants. Further clinical trials need to be carried out to
establish efficacy, tolerability and pharmacokinetics in paediatric transplant
recipients. Monoclonal antibody therapy (daclizumab and basiliximab) is an
exciting new development whereby T cell proliferation is inhibited by selective
blockade of interleukin (IL)-2 receptors. Preliminary results, when used in
combination with a standard immunosuppressive regimen, are good with respect to
incidence of acute graft rejection, host immune response and adverse effects.
FTY720 is a novel synthetic immunosuppressive compound which induces a
reduction in peripheral blood lymphocyte count through apoptotic T cell death
or accelerated trafficking of T cells into lymphatic tissues. Experimental
animal studies demonstrated synergistic action in combination with low dose
cyclosporin or tacrolimus, potentiating their immunosuppressive effects.
Further studies are being carried out to determine its potential for
application in organ transplantation. Despite this rapid development of novel
compounds, it will take many years before they may become part of standard
protocols in paediatric transplantation medicine. Further development and
research of efficacy and tolerability of existing drugs is, therefore,
vital. N. Ref:: 171
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[192]
TÍTULO / TITLE: - Immunosuppression with
limited toxicity: the characteristics of nucleoside analogs and anti-lymphocyte
antibodies used in non-myeloablative hematopoietic cell transplantation.
REVISTA
/ JOURNAL: - Cancer Treat Res 2002;110:39-49.
AUTORES
/ AUTHORS: - Bashey A
INSTITUCIÓN
/ INSTITUTION: - Blood and Marrow Transplantation Division,
University of California San Diego, Department of Medicine, UCSD Cancer Center,
La Jolla, CA 92093-0960, USA.
RESUMEN
/ SUMMARY: - The availability of two groups of
pharmacologic agents, the nucleoside analogs and anti-lymphocyte antibody
preparations of various specificities has enabled the development of NST.
Although these agents are significantly less cytotoxic than high-dose
alkylating agents and total-body irradiation (TBI), they are profoundly
immunosuppressive. Opportunistic infections such as the reactivation of
cytomegalovirus remain clinical obstacles when NST are performed using these
agents, especially in elderly and previously immunosuppressed patients. For
anti-lymphocyte antibody preparations, the degree of immunosuppression produced
and hence the risk of opportunistic infection varies depending upon specificity
of the antibody (broad versus narrow). Allergic reactions and infusion related
toxicity can occur with any antibody preparation, but the infusion of
muromonab-CD3 is sometimes associated with a particularly potent
cytokine-release syndrome. Although fludarabine has been the mainstay of
nucleoside analog usage for NST, the other nucleoside analogs-cladribine and
pentostatin are beginning to be investigated in this context. N. Ref:: 12
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[193]
TÍTULO / TITLE: - Post-transplant
diabetes: incidence, relationship to choice of immunosuppressive drugs, and
treatment protocol.
REVISTA
/ JOURNAL: - Adv Ren Replace Ther 2001 Jan;8(1):64-9.
AUTORES
/ AUTHORS: - Markell MS
INSTITUCIÓN
/ INSTITUTION: - Division of Transplant Nephrology, State
University of New York, Downstate Medical Center, Brooklyn, NY 11203, USA. mmarkell@hscbklyn.edu
RESUMEN
/ SUMMARY: - Post-transplant diabetes mellitus (PTDM)
is one of the feared complications of immunosuppressive therapy. Despite
advances, including the introduction of the steroid-sparing calcineurin
inhibitors, cyclosporine and tacrolimus, the incidence rate remains greater
than 10% to 30%, especially in minority populations. PTDM increases the
subsequent risk of both graft loss and patient death, and predisposes patients
to all complications of diabetes, including retinopathy and neuropathy.
Patients should be monitored closely, especially during the first 3 months
post-transplant, and treated aggressively, should glucose intolerance be
detected. Minimization of immunosuppression dose, diet, oral hypoglycemic
agents, and insulin have all been used in the treatment of PTDM, however, the insulin-sensitizing
agents have not been studied. It is hoped that newer immunosuppressive regimens
and, ultimately, the ability to achieve tolerance will eventually solve the
problem of PTDM. N.
Ref:: 53
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[194]
TÍTULO / TITLE: - Sirolimus: a
comprehensive review.
REVISTA
/ JOURNAL: - Expert Opin Pharmacother 2001
Nov;2(11):1903-17.
AUTORES
/ AUTHORS: - Kahan BD
INSTITUCIÓN
/ INSTITUTION: - Division of Immunology and Organ
Transplantation, University of Texas-Houston, 6431 Fannin, Suite 6.240,
Houston, TX 77030, USA. barry.d.kahan@uth.tmc.edu
RESUMEN
/ SUMMARY: - Sirolimus (Rapamune), Wyeth-Ayerst,
Madison, NJ) is a new, potent, immunosuppressant that is emerging as a
foundation for long-term immunosuppressive therapy in renal transplantation.
The drug acts during both co-stimulatory activation and cytokine-driven
pathways via a unique mechanism: inhibition of a multifunctional
serine-threonine kinase, mammalian target of rapamycin (mTOR). Although there
is no a priori reason to assume it, sirolimus displays a synergistic
interaction to enhance the efficacy of cyclosporin A (CsA). In trials wherein
the concentrations of CsA and sirolimus were tightly controlled, rates of acute
rejection episodes were < 10%, despite markedly reduced exposures to each
agent. In pivotal multi-centre blinded dose-controlled trials, the rates of
acute rejection episodes within 12 months following administration of 2 or 5 mg/day
sirolimus in combination with CsA and steroids were reduced to 19 and 14%,
respectively. Since the inhibitory effect of sirolimus disables virtually all
responses to cytokine mediators due to the widespread involvement of mTOR in
multiple signalling pathways, the agent is likely also to retard proliferation
of endothelial and vascular smooth muscle cells, an important component of the
immuno-obliterative processes associated with chronic rejection. The advantages
of this unique therapeutic action combined with an intrinsic lack of
nephrotoxicity are counterbalanced by myelosuppressive and hyperlipidaemic side
effects. Ongoing studies are assessing whether the long-term benefits of
sirolimus to permit reduction in exposure to or elimination of calcineurin inhibitors
ameliorate the progression of chronic nephropathy, the condition that erodes
long-term renal transplant survival. N.
Ref:: 108
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[195]
TÍTULO / TITLE: - Thrombotic
microangiopathy and cytomegalovirus in liver transplant recipients: a
case-based review.
REVISTA
/ JOURNAL: - Transpl Infect Dis 2003 Jun;5(2):98-103.
AUTORES
/ AUTHORS: - Ramasubbu K; Mullick T; Koo A; Hussein M;
Henderson JM; Mullen KD; Avery RK
INSTITUCIÓN
/ INSTITUTION: - Department of Infectious Disease, The
Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
RESUMEN
/ SUMMARY: - BACKGROUND: Thrombotic microangiopathy
(TMA) is a rare but potentially lethal complication encountered in solid organ
and bone marrow transplant recipients, requiring rapid recognition, diagnosis,
and initiation of therapy. Several potential causes have been identified in
this setting, including viral infections and medications. METHODS: We report a
case of TMA in a liver transplant recipient with active cytomegalovirus (CMV)
gastritis. A 41-year-old female presented 3 months after liver transplantation
with a 5-week history of nausea, vomiting, anorexia, and diarrhea. CMV serology
was donor seropositive and recipient seronegative (D+/R-). The
immunosuppressive regimen consisted of tacrolimus, mycophenolate mofetil, and
prednisone. Evaluation revealed CMV viremia with a high viral load and
intravenous ganciclovir was started. A decline in hemoglobin and platelets with
an increase in lactate dehydrogenase (LDH) warranted hematologic evaluation,
which revealed findings consistent with microangiopathic hemolytic anemia.
Ganciclovir and tacrolimus were discontinued. Intravenous immunoglobulin was
administered and daily plasmapheresis was initiated. As the patient’s blood
counts and LDH started to improve, ganciclovir was cautiously reinstituted. The
patient’s gastrointestinal symptoms gradually resolved and her blood counts
continued to improve with prolonged plasmapheresis (a total of 23
plasmapheresis sessions). Tacrolimus and possibly CMV infection were suspected
to be the cause for her TMA, and cyclosporine was substituted. CONCLUSIONS: TMA
is an important entity in the differential diagnosis of acute hemolytic anemia
in liver transplant recipients. Many cases seem to be medication-induced.
However, in treatment-resistant or relapsing cases, a possibility of
concomitant CMV infection should be considered. N. Ref:: 30
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[196]
TÍTULO / TITLE: - Novel approaches to the
treatment of chronic graft-versus-host disease.
REVISTA
/ JOURNAL: - Expert Opin Investig Drugs 2001
May;10(5):909-23.
AUTORES
/ AUTHORS: - Gaziev D; Lucarelli G
INSTITUCIÓN
/ INSTITUTION: - Unita Operativa di Ematologia e Centro
Trapianti Midollo Osseo de Muraglia, Azienda Ospedaliera S. Salvatore di
Pesaro, Italy.
RESUMEN
/ SUMMARY: - Chronic graft-versus-host disease (cGvHD)
continues to be the major problem in long-term survivors of allogeneic
haematopoietic stem cell transplants and is the principal cause of morbidity
and non-relapse mortality. Over the past twenty years, diagnosis, prophylaxis
and treatment of cGvHD have slowly evolved. An effective therapy for cGvHD is
designed to prevent complications through targeting the disease mechanisms.
None of the present therapies for cGvHD are successful in the majority of
patients. Conventional drugs in different combinations can control the disease
in approximately 50% of patients. Attempts to improve survival have led to
evaluation of several alternative approaches in the treatment of refractory
cGvHD with varying degrees of success. Clinical trials are needed to establish
the role of these new approaches in the treatment of cGvHD as first line or
salvage therapy without causing significant side effects. This review
summarises the currently available knowledge on conventional and new treatment
approaches for cGvHD. N.
Ref:: 119
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[197]
TÍTULO / TITLE: - New developments in
immunosuppressive therapy in renal transplantation.
REVISTA
/ JOURNAL: - Expert Opin Biol Ther 2002
Jun;2(5):483-501.
AUTORES
/ AUTHORS: - Gourishankar S; Turner P; Halloran P
INSTITUCIÓN
/ INSTITUTION: - Division of Nephrology and Immunology, University
of Alberta, Edmonton, Canada. gsita@hotmail.com
RESUMEN
/ SUMMARY: - The introduction of new immunosuppressive
agents and protocols has improved outcomes for renal transplant recipients by
decreasing the risk of rejection and by increasing the function and lifespan of
the allograft. This article reviews the major changes in the combinations of
therapies used: calcineurin inhibitors, target of rapamycin inhibitors,
mycophenolate mofetil, non-depleting monoclonal versus depleting monoclonal and
polyclonal antibodies for induction and increasing emphasis on protocols for
reduction or avoidance of steroids and calcineurin inhibitors. The new agents
with novel immunological targets such as anti-CD40 ligand, LEA29Y, FTY720,
anti-CD20 (rituximab, Rituxan, Mabthera) and anti-CH52 (alemtuzumab, Campath),
which are under development but have yet to survive the rigors of clinical
trials are also discussed. In the presence of low early rejection rates,
immunosuppressive therapy is setting new goals such as better graft function
(glomerular filtration rates), reduction in adverse effects such as
hypertension, hyperlipidaemia and drug toxicity and, above all, the prevention
of late graft deterioration. N.
Ref:: 156
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[198]
TÍTULO / TITLE: - Role of plasma
lipoproteins in modifying the toxic effects of water-insoluble drugs: studies
with cyclosporine A.
REVISTA
/ JOURNAL: - AAPS PharmSci 2002;4(4):E30.
●●
Enlace al texto completo (gratuito o de pago) 1208/ps040430
AUTORES
/ AUTHORS: - Wasan KM; Ramaswamy M; Kwong M; Boulanger
KD
INSTITUCIÓN
/ INSTITUTION: - Division of Pharmaceutics and
Biopharmaceutics, Faculty of Pharmaceutical Sciences, The University of British
Columbia, Vancouver, British Columbia, Canada V6T 1Z3. Kwasan@interchange.ubc.ca
RESUMEN
/ SUMMARY: - Lipoproteins are a heterogeneous
population of macromolecular aggregates of lipids and proteins that are
responsible for the transport of lipids through the vascular and extravascular
fluids from their site of synthesis or absorption to peripheral tissues.
Lipoproteins are involved in other biological processes as well, including
coagulation and tissue repair, and serve as carriers of a number of hydrophobic
compounds within the systemic circulation. It has been well documented that
disease states (eg, AIDS, diabetes, cancer) significantly influence circulating
lipoprotein content and composition. Therefore, it appears possible that
changes in the lipoprotein profile would affect not only the ability of a
compound to associate with lipoproteins but also the distribution of the
compound within the lipoprotein subclasses. Such an effect could alter the
pharmacokinetics and pharmacological action of the drug. This paper reviews the
factors that influence the interaction of one model hydrophobic compound,
cyclosporine A, with lipoproteins and the implications of altered plasma
lipoprotein concentrations on the pharmacological behavior of this
compound. N. Ref:: 28
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[199]
TÍTULO / TITLE: - Safety and tolerability
of caspofungin acetate in the treatment of fungal infections.
REVISTA
/ JOURNAL: - Transpl Infect Dis 2002 Mar;4(1):25-30.
AUTORES
/ AUTHORS: - Sable CA; Nguyen BY; Chodakewitz JA;
DiNubile MJ
INSTITUCIÓN
/ INSTITUTION: - Department of Infectious Diseases, Merck
Research Laboratories, West Point, Pennsylvania 19486, USA.
RESUMEN
/ SUMMARY: - Caspofungin acetate is the first member of
the novel echinocandin class of antifungal drugs to be marketed in the United
States. It has recently been approved for use in patients with invasive
aspergillosis who are refractory to or intolerant of conventional therapy.
Accordingly, its safety profile is particularly important to review. The safety
and tolerability of caspofungin have been examined in 623 persons, including
295 patients who received >/= 50 mg/day for at least one week in clinical
studies. In the 263 patients, given caspofungin in randomized double-blind
active-control trials to date, there have been no serious clinical or
laboratory drug-related adverse events; caspofungin was discontinued in only 2%
of these patients because of drug-related adverse experiences. Caspofungin may
have potentially important drug interactions with cyclosporine and
tacrolimus. N. Ref:: 13
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[200]
TÍTULO / TITLE: - Use of sirolimus in
kidney transplantation.
REVISTA
/ JOURNAL: - Prog Transplant 2001 Mar;11(1):29-32.
AUTORES
/ AUTHORS: - Podbielski J; Schoenberg L
INSTITUCIÓN
/ INSTITUTION: - University of Texas Medical School at
Houston, Houston, Tex., USA.
RESUMEN
/ SUMMARY: - Sirolimus, which has a distinctive
mechanism of action that inhibits cytokine-driven cell proliferation and
maturation, provides an exciting addition to the immunosuppressive regimen for
organ transplantation. A significant decrease in the number and severity of
rejection episodes has been noted when sirolimus is used; it also offers the
potential for patients to be withdrawn from steroids, making kidney
transplantation an option for many more potential recipients. Toxic conditions
such as hyperlipidemia, thrombocytopenia, and leukopenia become transient and
manageable with reduction of the sirolimus dose and/or countermeasure
therapy. N. Ref:: 9
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